APP1135277_Rice_Grant Proposal

GRANT PROPOSAL – 2016 Centres of Research Application ID: 1135277 

Excellence funding commencing 2017 CIA Surname: Rice 

Cover Page 

Centre of Research Excellence for Precision Medicine in Obstetrics 

Chief Investigators 

CIA: Professor Gregory E Rice, Acting Director, Centre for Clinical Research, Faculty of 

Medicine, The University of Queensland. Director, Centre for Clinical Diagnostics Centre 

for Clinical Research, Faculty of Medicine, The University of Queensland. 

CIB: Professor Paul Colditz, Director, Perinatal Centre for Clinical Research, The Royal 

Brisbane and Women’s Hospital. 

CIC: Professor Hayden Homer, Queensland Fertility Group and Centre for Clinical 

Diagnostics Centre for Clinical Research, Faculty of Medicine, The University of Queensland 

CID: Professor Murray Mitchell, Centre for Clinical Research, Faculty of Medicine, The 

University of Queensland, Faculty of Medicine, The University of Queensland. 

CIE Professor Matt Trau, Centre for Personalized Nanomedicine, Deputy Director Australian 

Institute for Bioengineering and Nanotechnology, The University of Queensland. 

CIF: Professor Jon Hyett, Head of High Risk Obstetrics, Royal Prince Alfred Women and 

Babies, Clinical Professor, Department of Obstetrics and Gynaecology, The University of Sydney. 

CIG: Doctor Carlos Salomon, Head, Exosome Laboratory Centre for Clinical Research, Faculty 

of Medicine, The University of Queensland, Director, Centre for Clinical Diagnostics Centre 

for Clinical Research, Faculty of Medicine, The University of Queensland. 

CIH: Professor H. David McIntyre, Director of Obstetric Medicine, Head of Mater Clinical 

School, University of Queensland. 

CII: Professor David Simmons, School of Medicine, Western Sydney University, Director of 

Endocrinology, Campbelltown Hospital and Director, Diabetes, Obesity, Metabolism Translational 

Research Unit, South Western Sydney Local Health District 

CIJ: Professor Sailesh Kumar, Head, Obstetrics & Gynaecology, Mater Clinical Unit, Faculty of 

Medicine, The University of Queensland 

Associate Investigators 

Professor Leonie Callaway, Head, Royal Brisbane Clinical School, and Senior Specialist in 

Obstetric and Internal Medicine at the Royal Brisbane and Women's Hospital. 

Dr Marloes Dekker, Senior Postdoctoral Researcher, School of Biological Sciences The 

University of Queensland 

Associate Professor Gregory Duncombe, Chair, Maternal Fetal Medicine Subspecialty 

Committee RANZCOG, Co-Director of Queensland Ultrasound for Women, 

Professor Anne Marie Hennessy, Dean, School of Medicine, Western Sydney University. 

Professor Karen Moritz, Director, Children’s Health Research Centre. The University of 

Queensland. 

Ds Sarah Reed, Head Mass Spectrometry Facility, Center for Clinical Diagnostics 

Professor Alan Rowen, Director, Australian Institute for Bioengineering and Nanotechnology 

Associate Professor David Whiley, Pathology Queensland 

Associate Professor Anusch Yazdani, Director of Clinical Research and Development, 

Queensland Fertility Group 

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Response to Assessment Criteria 

1. Generate new knowledge that leads to improved health outcomes 

Pregnancy outcome in Australia 

The foundations of health throughout life are laid down during fetal development. Complications of 

pregnancy that compromise fetal development have profound effects not only on the immediate 

outcomes of pregnancy but also on the life-long disease risk susceptibility of the offspring. 

300,000 babies are born in Australia each year. The growth and development of more than 45,000 

of these babies is compromised by complications of pregnancy. Complications of pregnancy, such 

as: pregnancy-induced maternal high-blood pressure (preeclampsia, PE); pregnancy-induced 

diabetes (gestational diabetes mellitus, GDM); small for gestational age (intrauterine growth 

restriction, IUGR), stillbirth and preterm birth (delivery before 32 completed weeks of pregnancy, 

PTB), result in significant adverse health outcomes for the newborn; an increased short term risk of 

mortality and morbidity and an increased life time risk of metabolic and cardiovascular disease. 1-3 

Each year in Australia, 150,000 pregnancies are lost before 20 weeks of pregnancy (miscarriage), 

2000 are lost after 20 weeks (still birth), 2,500 babies die during the first 28 days of life and 800 

more before their first birth day. Poor pregnancy outcome (defined by these data) is a significant 

health and economic issue in Australia and, even more so, in developing nations. 

In most cases, poor pregnancy outcome is not anticipated or diagnosed early enough to significantly 

change health outcomes. Currently available tests are either not of sufficient accuracy for screening 

the general obstetric population or lack sufficient evidence-based data to define clinical utility and 

justify implementation into standard practice. 

Pregnancies resulting from Assisted Reproductive Technologies (ART) also suffer significantly 

higher rates of adverse outcomes such as preterm birth and low birthweight. Embryo screening for 

the steadily rising ART population offers an opportunity to identify and prevent at-risk pregnancies 

at the pre-implantation stage, but remains undeveloped. 

Most women who are triaged into high-risk obstetric units on the basis of poor previous obstetric 

history ultimately have uncomplicated pregnancies, whilst on the other hand it is those assumed to 

be low risk who comprise a large proportion of complicated pregnancies. Thus, critical health care 

resources are wasted and those who require high-risk care may not gain access to potential 

therapies. Early detection of risk is the first step in implementing efficacious treatment and 

improving pregnancy outcomes. 

One exception and a proof-of-concept establishing the feasibility of the approach to be used in this 

CRE is the work of CI Hyett. CI Hyett has implemented and evaluated first trimester screening for 

PE and reduced the prelevance of this complication of pregnancy at the Royal Prince Alfred 

Hospital in Sydney. 4 Based on the current performance of the screening test, however, only 1 in 

28 women triaged to treatment (i.e. low dose aspirin) would have developed PE. The current 

recommendations of the American College of Obstetricians and Gynecologists remain taking a 

detailed medical history to assess a patient's risks for developing PE but not using laboratory and 

imaging screening tests. 

There is a clear and well defined need to further improve screening test performance. 

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Pregnancy is a stress test for life – a window into future health 

What happens during pregnancy informs us about the likelihood of developing adult disease, not 

only for the newborn 3 but also the mother. 5,6 Pregnancy, therefore, has been described as a 

stress test 7 and a window into future health. 8,9 

It is now well established that women who experience complications of pregnancy are at higher risk 

of developing obesity, diabetes and cardiovascular disorders in adult life. 10 In response, the 

American Heart Association acknowledged PE, GDM and IUGR as pregnancy-related risk factors 

for cardiovascular disease in the 2011 update of the Effectiveness-based Guidelines for the 

Prevention of Cardiovascular Disease in Women. 11 

Women who develop GDM, one of the most 

common maternal complications of pregnancy, 

have a 4- to 7-fold greater risk of developing type 

2 diabetes 12 ; an increased risk of developing 

metabolic syndrome 13 ; and a 66% to 85% higher 

risk of cardiovascular disease, including coronary 

artery disease, myocardial infarction, and/or 

stroke. 14 At present, there is a paucity of evidence 

with regard to the efficacy of a strategy of early 

identification and treatment of GDM prior to 24 

weeks of gestation. 

Women who develop PE during pregnancy are 4-fold more likely to develop hypertension later in 

15 16 

life and are twice as likely to develop heart disease, stroke and thrombosis in the future. 

Women with a previous history of preterm delivery, stillbirth or fetal growth restriction are 

similarly at increased risk of developing cardiovascular disease (~2-fold). 17 

Improving health outcomes for mothers and babies is a National priority, particularly for our 

indigenous populations (Closing the Gap, Department of Health, 11 October 2016) and remote 

communities. 

To achieve this objective requires: 

“Early detection and treatment may 

potentially improve outcomes. 

However, there is a dearth of 

evidence in this area.” 

ADIPS Consensus Guidelines for the 

Testing and Diagnosis of 

Hyperglycaemia in Pregnancy in 

Australia and New Zealand 2014 

Co-author CI McIntyre 

• more effective means to identify women who are at risk of developing complications of 

pregnancy; and 

• the implementation of effective prevention and/or intervention strategies. 

The earlier we can identify women who are at risk of developing complications of pregnancy, the 

greater the opportunity to improve the health outcomes for both mother and baby. This is the 

overall, ongoing objective of this CRE for Precision Medicine in Obstetrics. 

This CRE will build capacity by establishing a translational pipeline between innovation and 

technology intensive entities (AIBN, UQCCR) and clinical practice (including pathology service 

delivery, Pathology Queensland). This pipeline will promote clinical engagement, the opportunity 

to deliver end-user requirements. It will also provide unique training opportunities, new career 

pathways and development of future leadership in obstetric medicine and industry-standard 

translational research. 

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By investigating new classes of biomarker (exosomal) and implementing new genomic testing 

approaches (Single Drop DNA analysis); developing new multiple biomarker algorithms for risk 

assessment during pregnancy; and delivering clinical and health economic outcome data on their 

performance, this CRE will create tangible outcomes within five main aims: 

Generate new knowledge on the role of exosome signalling in embryo development by 

characterising developmental changes in the packaging and release of exosomes from blastocysts 

and the effects of blastocyst-derived exosome on decidua phenotype and implantation efficiency 

(CIs Homer, Salomon, Trau, Colditz, Rice; AIs Yazdani, Rowan). The data obtained from these 

studies will ultimately contribute to the development of new precision medicine management 

strategies for improving embryo quality, implantation efficiency and pregnancy and neonatal 

outcome. 

Identify and characterise biomarkers of complications of pregnancy that are present in biofluids of 

pre-symptomatic women that can be incorporated into existing or novel screening tests to improve 

risk assignment (positive predictive value) and patient triage to appropriate treatment (CIs Hyett, 

McIntyre, Kumar, Simmons, Salomon, Trau, Mitchell, Rice; AIs Moritz, Duncombe, Reed). 

Studies will be conducted within the Centre for Clinical Diagnostics (a NATA accredited 

ISO17025, medical device development environment) in accordance with ISO13485 guidelines. 

Develop and clinically evaluate a new generation of first trimester screening tests for GDM and PE 

by conducting prospective Phase 3 biomarker and clinical intervention trials translating research 

outcomes into clinical applications (CIs Hyett, McIntyre, Simmons, Kumar, Salomon, Trau, 

Mitchell, Rice; AIs Moritz, Duncombe, Reed). 

Facilitate collaboration across three national universities (The University of Queensland, University 

of Sydney, Western Sydney University), four hospitals (Royal Brisbane & Women’s Hospital, 

Mater Hospital, Royal Prince Alfred Hospital, Campbelltown Hospital) an international hospital 

network (Ochsner Health System, New Orleans. La, USA) and a State Pathology Department 

(Pathology Queensland). These collaborations will develop the health and medical research 

workforce in clinical obstetrics and neonatology, reproductive medicine and assisted reproductive 

technologies, in vitro diagnostics, nanotechnology and molecular biology. 

Inspire and train young clinicians and scientists to use the latest technological advances in 

reproductive medicine within an international industry standard environment (ISO17025, 

ISO13485) that focuses on end-user requirements and translational improvement in healthcare and 

commercial enterprise. 

The CRE team has the expertise, experience and capacity to deliver and implement new pregnancy 

screening tests that will improve the allocation of health care services and reduce the incidence and 

severity of complications of pregnancy and, thereby, improve outcomes for both mother and baby. 

Key Programs Conducted by the CRE 

This CRE for Precision Medicine in Obstetrics will geerate new knowledge, build translational 

capacity by creating a translational pipeline between T1 in-human medical device development, T2 

clinical evaluation of In Vitro Diagnostics, T3 clinical health outcomes and T4 health economic 

data to inform policy change. These objectives will be achieved within four CRE Core Programs. 

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PROGRAM 1: Exosomal Signalling In Pregnancy 

Program 1 is a discovery program that seeks to increase knowledge about the role of exosomal 

signalling in cell-to-cell communication during normal pregnancy and its complications. The 

program will be conducted in collaboration between AIBN and the UQ Centre for Clinical 

Diagnostics; the latter is one of only two such facilities in Australia that are NATA accredited for 

ISO17025 (General requirements for the competence of testing and calibration laboratories, 

codified for research). 

Research Questions 

• To characterize developmental changes (up to day 5) in the release and content of exosomes 

from human blastocysts, in vitro. 

• To establish the mechanism(s) by which blastocyst-derived exosomes interact with decidua 

cells; exosomes uptake and signal delivery. 

• To define the effects of blastocyst-derived exosomes on decidua cell phenotype and 

blastocyst attachment. 

Objectives: To define the role of exosomal signalling during embryo development. In partnership 

with the Queensland Fertility Group (AI Yazdani), Program 1 will deliver new knowledge that will 

allow the development of novel methods for non-invasive embryo testing (see Program 2) and 

ultimately the development of new treatments to improve implantation efficiency. The Program 

utilises established methodologies and expertise developed by the CIs and AIs in the study of 

human placental exosome biology (CIs: Salomon, Rice, Mitchell; AIs: Duncombe, Reed). 

Study Rationale: Exosomal signalling is a formative and burgeoning area of clinical research and 

one that offers great opportunity. Opportunity not only in terms of generating new knowledge 

about a novel cell communication system (i.e. exosomal signalling) but also in terms of identifying 

tissue- specific biomarkers and in developing naïve and engineered endogenous exosome-, and 

synthetic exosome-based therapeutics and drug delivery systems. These opportunities arise as a 

result of a paradigm shift in our understanding of how cells communicate and, in particular, the 

recognition of the role of exosomes in intercellular signalling. 18 Exosomes are small (40-100 nm), 

stable lipid bilayer nanovesicles that are formed by the inward budding of multivesicular bodies. 19 

Exosomes are package with tissue specific signalling molecules and once released are capable of 

regulating proximal and distal cell function. Exosomes are a unique source of biomarkers, 

therapeutics and theranostics as their content is stabilised and protected against enzymatic 

degradation; they are biocompatible, permeable to biological barriers; of low toxicity and low 

immunogenicity; able to be loaded with specific signalling molecules; and may be re-engineered or 

have molecules addressed to their surface, conveying exosome targeting capabilities to cells bearing 

cognate receptors. 20 

There is a paucity of data on exosomal signalling by the blastocyst and the functional role of 

exosomes in embryo development. The aim of this Core Program is to advance understanding of the 

role of exosomes in embryo development. This will result in the development of more informative 

diagnostics and opportunities for new therapeutic interventions. 

Proposed Research: In vitro discovery studies will be conducted to characterise: the release 

(number and size distribution) of exosomes from human blastocysts using nanoparticle tracking 

analysis (CI Salomon) 21 ; exosome protein (AI Reed, SWATH tandem mass spectrometry 22 and 

miRNA content 23 ; and the effect of blastocyst-derived exosomes on endometrial and endothelial 

cell phenotype using real-time cell imaging. 24 Exosome uptake by target cells will be assessed 

fluorescently-labelled exosomes (PKH67 green 25 ). Effects on cell phenotype will be defined using 

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real-time cell imaging 25 ; discovery-based proteomic analysis (Sequential Windowed Acquisition of 

All Theoretical Fragment Ion Mass Spectra, SWATH MS/MS; AI Reed 22 ) and targeted genomic 

methylation profiling (CI Trau) 26 , respectively. Studies will utilise human embryo-conditioned 

medium that we have obtained from our collaborative partner Queensland Fertility Group (AI 

Yazdani). The effects of blastocyst-derived exosomes on embryo attachment and invasion will be 

performed using in vitro pre-clinical models (CIs Mitchell and Homer). 27,28 

Significance: This T1 CRE Program will build capacity and generate knowledge that will inform 

clinical practice via the identification of potential biomarkers of embryo quality and consequently 

improving the rate of successful pregnancy. The Program is a direct collaborative engagement with 

healthcare service provider (Queensland Fertility Group), designed to meet a specific clinical need. 

PROGRAM 2: Non-invasive embryo testing 

Program 2 is a phase 2 biomarker trial; prospectively collected, retrospectively stratified cohort 

study) to clinically evaluate non-invasive embryo screening. 

Research Question: Are biomarkers (exosomal and genomic) present in day 3 and/or day 5 human 

embryo-conditioned media that correctly classify embryo quality based on pregnancy and neonatal 

outcome? 

Objectives: To establish the efficacy of exosomal and genomic biomarkers to correctly classify 

embryo quality on the basis of pregnancy and neonatal outcome. 

Rationale: Early prediction of the viability of in-vitro developed embryos before the transfer to a 

recipient still remains challenging. Presently, the predominant non-invasive technique for selecting 

viable embryos is based on morphology, where parameters such as rates of cleavage and blastocyst 

formation as well as developmental kinetics are evaluated, mostly subjectively. The per-oocyte 

pregnancy rate during IVF is surprisingly low with 7% or less of all oocytes producing a live-birth. 

Because of this low efficiency, multiple cycles of IVF are often required and in many areas of the 

world, multiple embryos are replaced leading to unacceptable rates of high-risk multiple 

pregnancies. Techniques capable of identifying the best quality blastocysts would greatly 

streamline and increase efficiency of IVF practice. 

Study Design: The clinical utility of biomarkers identified in Program 1 (including exosomal 

biomarker already identified in preliminary studies) will be determined in a phase 2 biomarker trial. 

Embryo-conditioned medium (n=2000) will be prospectively collected (QGF, AI Yazdani) and then 

retrospectively stratified on the basis of pregnancy and neonatal outcome. The efficiency of 

biomarkers to correctly classify cases will be established. 

Study endpoints: The primary endpoint (and stratification criterion of the study) will be live birth at 

term with a composite perinatal/health/neurodevelopment endpoint described in more detail below. 

Secondary endpoints are: the proportion of complicated vs uncomplicated pregnancies (i.e. GDM, 

PE, IUGR, spontaneous preterm birth and early pregnancy biomarkers). 

Newborn outcomes and screening: Each of the pregnancy cohort Programs in this CRE has 

newborn outcome as an additional final target for assessment of pregnancy outcome. Important 

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major newborn outcomes will be assessed in the following established ways which take into 

account a balance of data quality, cost, depth and availability of normative/comparative data: 

1. Birth data from the Perinatal Data Collection: livebirth/stillbirth, gestational age, growth 

parameters, need for resuscitation, Apgar scores, admission to neonatal nursery 

2. Routinely collected data to age 2 years: Medicare data (GP visits), Qld Hospital admitted 

patient data collection, QHAPDC (hospital admission diagnoses) 

3. Assessment at age 2 years: Bayley III assessment (neurodevelopment), medical assessment, 

health questionnaire, anthropometric measurements. 

These data sources will be used to define (i) a composite endpoint of low/high morbidity required in 

individual studies above, (ii) neurodevelopmental outcome, (iii) disease diagnostic categories, (iv) 

health service utilisation. 

Newborn screening is currently performed for a limited range (typically < 20) of genetic disorders 

with no two countries' screening programs the same. 29 Progress in technology has led to an increase 

in the number of conditions screened for, with tandem mass spectrometry which detects abnormal 

metabolites, now the dominant technology. Agreed criteria for screening include: a demonstrable 

benefit from early diagnosis; a suitable test with high specificity and sensitivity; a system of 

confirmation of results, counselling, treatment and follow-up; and the balance of harms and benefits 

is positive. Whole genomic testing is now available at a rapidly falling cost. However, its possible 

application to newborn screening poses a complex set of ethical, legal, and societal questions, 

particularly with the identification of mutations without knowledge of whether they represent 

pathological or benign polymorphisms. 

In this context to capture the best of new technology and to avoid the issues raised by whole 

genome screening, we propose a screening development and trial using a new relatively low cost 

technology developed by CI Trau to screen for 96 (as opposed to the current < 20) known genetic 

mutations that best meet agreed screening criteria. We will develop a 96-well plate using the 

multiplex PCR/SERS method 30 and evaluate it for its suitability to replace and enhance current 

newborn screening. 

Sample Size Determination: Sample sizes were established using Blume’s method 11 to allow 80% 

power to detect a 0.10 difference between an AUC of the new screening approach and current 

morphology-based embryo assessment. 

Analysis of Diagnostic Efficiency Outcomes: Statistical analyses have been developed to assess the 

hypothesis that a multimarker new screening test has greater discriminatory power to correctly 

classify embryos that result in normal pregnancy and neonatal outcome in comparison with current 

morphology based embryo assessment. Diagnostic performance will be summarized through the 

calculation of ROC curves, and by calculation of the area under the ROC curve (CI Rice 31,32 ). The 

difference in AUC between the diagnostics will be tested using a bootstrap procedure. 

Significance: The identification of biomarkers in embryo-conditioned media that are predictive of 

pregnancy outcomes will facilitate the development of non-invasive tests to aid in the assessment of 

embryo quality for assisted reproductive technologies. 

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PROGRAM 3 - First trimester Screening 

Program 3 will establish the classification efficiency of exosomal and genomic biomarkers present 

in maternal plasma at 12-14 week of pregnancy for complications of pregnancy. The data obtained 

will inform the composition of the screening algorithms used in Program 4. 

Research Question: To determine the performance of exosomal and genomic biomarkers present 

in maternal plasma, at 12 to 14 weeks of pregnancy and to classify women who have complicated 

and non-complicated pregnancy outcomes. Based on the outcome of these analyses, biomarkers 

will be selected for inclusion in multivariate screening assays to be used in Program 4. 

Study Rationale: Early identification of women at risk of developing complications of pregnancy 

is the first step in reducing the prevalence and severity of such complications. Currently available 

first trimester tests are either not of sufficient accuracy for first trimester of population-based 

screening or lack sufficient evidence-based data to define clinical utility and justify implementation 

into standard practice. 33 Our team has been developing multiple biomarker tests to identify women 

at 11-14 weeks of pregnancy who are at increased risk of subsequently developing complications of 

pregnancy. In order to introduce these tests into routine screening for the general obstetrics 

population, robust estimates of their classification efficiency and prognostic performance must be 

established. Thus, the primary objectives of Program 3 are to determine the classification 

performance of early-pregnancy screening tests to identify women at risk of developing 

complications of pregnancy and to identify and clinically evaluate additional exosome-associated 

and genomic biomarkers for inclusion in the screening test to improve test performance. The 

program is innovative in the development and application of placenta-specific exosomes for in vitro 

diagnostic screening tests and the application of high throughput and low cost genomic biomarker 

screening. 

Study Design: This is a multi-centre Phase 2 biomarker trial conducted at the RBWH, Mater 

Hospital, Campbelltown Hospital and the RPA Hospital. We are already screening 2000 women a 

year and store serum samples post first trimester analysis and collect pregnancy outcome data to 

describe five common adverse outcomes: spontaneous PE (early and late), GDM, PTB, IUGR. It is 

planned that 4758 women attending obstetric clinics will be recruited into this study. The 

involvement of four recruitment sites allows validation across different patient populations. 

Following recruitment and the recording of demography, past medical/surgical history and current 

medications, study participants will have a blood specimen collected and stored. Samples will be 

retrospectively stratified into two groups viz normal pregnancies and pregnancies complicated by 

GDM, PE or preterm birth. Plasma samples will be assayed for candidate biomarkers (i.e. 

biomarkers for which we have already completed proof-of-principle studies or are currently part of 

an existing algorithm (i.e. PE algorithm - CI Hyett). In a discovery component of this program, 

additional exosomal and genomic biomarkers present in first trimester plasma will be evaluated for 

inclusion in risk assessment algorithm. Classification performance will be summarized through 

ROC curve analysis and by calculation of the area under the ROC curve. 12 

Primary Endpoint: The primary study endpoint is the comparison of the area under the receiveroperator-characteristic 

curve for the new algorithms verse the standard risk assessment guidelines 

for identification of women at risk of developing complications of pregnancy. 

Sample Size Determination: Sample size was established using Blume’s method 11 to allow, at 

least, 80% power to detect a 15% difference between AUCs [based on a sample size calculation 

using P1 0.235 | P2 0.01475 | alpha=0.05 | 1-beta = 0.8 and assuming 20% women defined as high 

risk of early PE/late PE/IUGR or GDM through screening]. 

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Exosome Isolation and Processing: An exosome-enriched fraction will be prepared from clinical 

samples using ultra- and nano-filtration and disruption and solubilisation of exosomes. This 

extraction method allows direct translation of assays into routine clinical pathology platforms. The 

resultant soluble phase is available for direct assay on existing medical device approved, pathology 

platforms. 

Early pregnancy Screening Assay Exemplar: In proof-of-principle studies for GDM screening 

completed to date, we have identified a panel of 5 exosomal biomarkers (exosome-associated IL6, 

IL8, IL10, IFN γ, TNFα) that are strongly correlated with the subsequent development of 

gestational diabetes. First trimester HbA1c and Oral Glucose Tolerance Test will be determined on 

existing hospital pathology platforms. Furthermore, each assay will include defined positive and 

negative controls as well as internal standards. 

Receiver-operator-characteristic curve analysis: The ROC curve for the reference classification 

will be based simply on the RANZCOG and ACOG risk assignment guidelines. ROC curves for 

new classification algorithms will be based on the predicted probability of membership of the 

specific complication of pregnancy group. The area under the ROC curve (AUC) will be calculated 

using the Wilcoxon statistic. 34 The difference in AUC between methods will be tested using a 

bootstrap procedure. 35 Results from individual algorithms will be aligned with clinical data and 

pregnancy outcome and their performance compare to that of the current practice high assessment. 

That is, in the case of PE, the algorithm used by CI Hyett or previous obstetrics history and known 

risk factors for GDM and preterm birth. Tests will be developed in compliance with GLP 

principles as codified by ISO17025 and ISO13485, thus, enhancing translational and 

commercialisation opportunities. The final product will be a Class II medical device that will be 

commercialised with our industry partner; SeraCare LLC and Pathology Queensland (AI: Whiley). 

Significance: The outcome of this study will be the delivery of Level 2 clinical evidence on the 

performance; providing robust estimates of the classification performance (i.e. case-control cohort 

analysis) of multivariate models for the early pregnancy identification of women who subsequently 

develop PE, GDM or preterm labour. The outcome of this Program will inform Program 4 Triage to 

Treatment. The significance of this study resides in the delivery of a higher performance, single 

modality screening for early pregnancy risk assignment for complications of pregnancy that may be 

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implemented within routine pathology. The data obtained will inform and facilitate the development 

and clinical uptake early pregnancy screening and triage to treatment. 

Program 3 formalises an In Vitro Diagnostic medical device development core that is NATA 

accredited for ISO17025, complies with ISO13485. During the life of the CRE, application will 

also be made for accreditation for ISO15198 (Medical Testing). As such, this Program will be the 

only such accredited facility in Australia. It will provide a unique clinical research, development 

and training environment for scientific and clinical practitioners and an enabling capacity for 

leadership development. 

PROGRAM 4: Triage to High-risk Management 

First trimester screening algorithms for PE, IUGR and GDM have already been developed. There 

are a number of processes that need to be completed before these tools for individualised precision 

medicine can be robustly applied to population based screening. First, continued algorithmic 

development with inclusion of other biomarkers (Program 2) will improve screening efficacy 

(sensitivity, specificity and predictive values) and facilitate development of algorithms for preterm 

birth. Second, these algorithms need validation in separate populations to demonstrate applicability 

and consistency in performance. Third, the impact of preventative interventions applied based on 

the findings of first trimester screening (and therefore the value of prediction and prevention) needs 

to be demonstrated. These processes can potentially be completed simultaneously in multicentre 

randomised controlled trials that enrol patients prior to screening, randomising them to an 

intervention on the basis of the initial predictive test result. 

Research Questions: 

• Can the performance of current first trimester screening algorithms be reproduced in 

multiple centres with different population groups? 

• Can screening efficacy be improved by inclusion of other exosome or genome derived 

biomarkers? 

• Are preventative interventions (aspirin for PE and IUGR; metformin for late PE; diet and 

lifestyle advice / metformin / probiotics for GDM; progesterone / cerclage for preterm 

labour) effective in reducing disease prevalence for women defined as being at high risk of 

an adverse pregnancy outcome? 

Study Rationale: There is a clear need to collect more evidence-based data to define the clinical 

utility of first trimester risk assignment algorithms and to examine the impact of preventative 

therapeutic interventions. We have already developed multivariate algorithms to classify risk for 

subsequent development of PE, IUGR and GDM. The tests can variously be criticised for poor 

sensitivity (IUGR, late onset PE) and/or positive predictive value (early onset PE) and may be 

improved by including exosomal biomarkers or genomic markers. Novel algorithms, based on 

inclusion of these factors, can be compared to our current standards by comparing test performance 

through calculation of screening efficacy (sensitivity and specificity and positive and negative 

predictive values) and receiver operator characteristic curve analysis. Screening and identification 

of risk is only of value if preventative strategies are available that improve health outcomes. A 

number of interventions that prevent PE/ IUGR, GDM and spontaneous preterm birth have been 

proposed. Application is typically impacted by poor prediction of a high-risk group. The combined 

prediction and prevention strategy therefore needs assessing through a multicentre randomised 

controlled study. 

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Study Design: This is a multi-centre clinical trial that is to be conducted at the Royal Brisbane and 

Women’s Hospital and Mater Hospital, Brisbane; Campbelltown Hospital; and the Royal Prince 

Alfred Hospital, Sydney. Women will be randomised to intervention or control arms. In the 

intervention arm biomarker-stratified analysis will be used to predict risk of PE, IUGR and GDM 

and high risk women will be treated with the intention of reducing the prevalence of disease. In the 

control arm, the data for biomarker –stratified analysis will be collected (and risks calculated after 

delivery) and pregnancies will be managed according to normal protocols. The primary outcome 

measure will be a composite of the prevalence of early and late onset PE, IUGR and GDM. The 

baseline prevalence of these disorders is 23.5% [0.5% early PE +3.0%late PE +5% IUGR + 15% 

GDM] and, based on available data of the effectiveness of first trimester screening and prevention 

strategies we anticipate a reduction to a prevalence of 14.75% [0.25% early PE +2.0% late PE + 

2.5% IUGR +10% GDM] (a 37% reduction in prevalence of disease). Demonstrating this 

difference requires randomisation of 732 women to intervention / control arms which, based on a 

20% screen positive rate and a 30% default rate in recruitment will require enrolment of 4758 

women in the screening program [based on a sample size calculation using P1 0.235 | P2 0.01475 | 

alpha=0.05 | 1-beta = 0.8 and assuming 20% women defined as high risk of early PE /late PE / 

IUGR or GDM through screening]. Analysis of data collected in women randomised to no 

intervention will allow validation and improvement of screening algorithms and the development of 

a validated algorithm for prediction of preterm birth that can be tested for preventative efficacy at a 

later date. 

Sample Size: Determination: Sample sizes were established using Blume’s method to allow, at 

least, 80% power to detect a 15% difference between AUCs. 

Significance: The successful completion of this study will provide Level III evidence for the 

implementation of early pregnancy screening for PE and permit the robust assessment of the 

efficacy of treatments for the prevention of PE, IUGR and GDM. Analysis of data collected in 

women randomised to no intervention will allow validation and improvement of screening 

algorithms for these complications of pregnancy as well as for preterm birth. 

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2. Promote effective transfer of research outcomes into health policy and/or practice 

This CRE increases capacity and research translation by bring together an exceptional 

multidisciplinary team who are nationally and internationally recognised healthcare professionals 

and researchers. The team is ideally placed to develop and implement new screening applications 

and medical devices into practice and to champion the update of practice and policy change. 

The governance structure of the CRE will include a Board of Management (CIs, + UQCCR Quality 

Assurance Office + Admin Officer), The Board will provide strategic planning and achievement of 

project KPIs. CRE Programs will be managed under an international quality management system 

and in compliance with FDA 21 CRF part 820. The ongoing review requirements of is code will be 

the responsibility of the Clinical Review Committee (McIntyre, Simmons, Colditz, Callaway, 

Hennessy + UQCCR QU officer + Health Economist). 

The Centre for Clinical diagnostics has already established an Industry Advisory Committee 

(Chaired by Prof Maree Smith, UQ). This committee will also facilitate and provide advice 

regarding industry engagement, CRE placement and career development. The currently community 

engagement activities of CRE members will be consolidated within the governance structure of the 

CRE to further enhance educational and awareness opportunities. 

The CRE will promote the transfer of research outcomes into health policy and practice as follows: 

2.1 The development and evaluation of new In Vitro Diagnostic screening tests for regulatory 

agency approval is requisite to implementation into practice. This will be achieved through the 

engagement of the CRE’s Biomarker Discovery and IVD Development capacity within the 

AIBN (Trau, Rowan), the Centre for Clinical Diagnostics (Rice, Salomon, Mitchell, Reed) and 

Pathology Queensland (Whiley) with Clinician Research teams directly engaged in high-risk 

patient management and the evaluation of new practice and policy - ART (Homer, Yazdani); 

complications of pregnancy (Hyett, McIntyre, Simmons, Kumar, Moritz, Duncombe); and 

pregnancy and neonatal outcome (Colditz, Moritz). As the IVDs are developed in compliance 

with ISO13485, they would be suitable for direct implementation within pathology services, 

such as Pathology Queensland or as niche diagnostics within the Centre for Clinical 

Diagnostics (once accredited for ISO15189) and be available for patient management. The 

intended label use of the tests (i.e. the uses submitted to TGA and/or FDA for approval as a 

Class II medical device, 510K submission) is as an IVD MIA to aid in the diagnosis of 

complications of pregnancies. Our team has a well-established track record in: the diagnosis 

and clinical management of complications of pregnancy, the discovery of biomarkers (using 

both protein display technologies and mass spectrometry-based approaches) 36-38 ; exosome 

biology 39,40 , in the development and evaluation of in vitro diagnostics 31 ; in the collection 

large pregnancy cohort 41 ; and in commercialisation and delivery of new diagnostics to market. 

2.2 Generation of technology advances, intellectual property and patents. It is anticipated the 

CRE will generate substantive advances in the development of devices and applications for 

rapid and or point-of-care use. Such devices would include, for example, hand-held devices for 

single drop DNA neonatal screening and/or embryo quality. New screening algorithms for 

assessing embryo quality and the risk of complications of pregnancy that have been 

appropriately evaluated and deliver increased sensitivity and specificity would represent 

significant intellectual property and the basis of patent applications. CRE members have a 

strong track record in patent development and commercialisation (e.g. Rowan, Trau, Homer, 

Rice). The development of new medical devices that more effectively informs the allocation 

of health care resources and patient management is a primary practice outcome of this CRE. 

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2.3 Best Practice Integrated Pregnancy Care Service. In addition, to the traditional modes of 

research outcome transfer, including: publication, profession and lay communications; patent 

submission; influence in peak professional bodies, this CRE will implement its research 

findings and education and training principles by establishing a best practice integrated 

pregnancy care service. Through its Clinical Practice Advisory Committee (Hyett, McIntyre, 

Simons, Colditz, Hennesey, Dumcombe, CEO, Health Economist, QA Officer, Project Officer) 

the CRE will deliver an iconic integrated pregnancy care service to deliver a best practice highrisk 

pregnancies care model. The healthcare model will dynamically and directly incorporate 

robustly validated clinical research advances into practice and provides a unique platform for 

workforce training and development. The Service will be coordinated by an independent web 

presence and serve not only as a referral portal for high-risk management but also as an enduser 

(community) education and awareness instrument. 

2.4 Health Economics and Policy Unit With the successful development of more effective 

screening test, the demonstration of clinical outcome benefit, the CRE’s Health Economics and 

Policy Unit (Health Economist, CEO, QA Officer, CRE Project Office) will generate health 

economic analyses for each of the practice changes supported by the work of the CRE 

enterprise and engage with the professional colleges and the TGA to provide an economic 

rationale for change. The Unit will facilitate and support T4, population-based activity that will 

bring the tests and the applied knowledge accrued under Programs 1, 2, 3 and 4 to 

implementation in the public health sphere. In addition, the Unit will conduct analyses of the 

economic impact of pre-clinical data failure in Australia and aid in generating a green paper on 

the Research Quality in Australia to enable an informed review of research quality management 

across the sector. 

2.5 Clinical and Research Champions Change in clinical practice and ultimately policy not only 

requires robust clinical evidence but “champions of change”; clinicians and scientists who are 

able to community the benefit of change in the health care system to their peers. Each CRE CI 

will be a change champion for the CRE research outcomes and leverage their professional 

networks as follows: 

2.5.1 Biomarker discovery and identification, development of in vitro diagnostics for clinical 

evaluation, validation and regulation will be championed by the AIBN- and UQCCR-based 

team of CIs Rice, Mitchell, Trau, Salomon, Rowan. The ISO17025 and ISO13485 

accredited environment enables the production of robust, reproducible industry-ready 

findings that will feed directly into a translational pathway. CI-Rice has served in leadership 

roles with the Australian Perinatal Society, the Perinatal Society of Australia & New 

Zealand the International Federation of Placenta Associations. CI-Rice is well placed to 

implement processes to ensure research integrity and alignment of academic research with 

industry standards to improved translational efficiency. CI-Mitchell is President Nominee 

of The Society for Reproductive Investigation in 2016 and will chair the Society’s annual 

meeting in Paris in 2019. He is Fellow ad eundem, Royal College of Obstetricians and 

Gynaecologists. CI-Mitchell has been at the forefront of organising global approaches to the 

issues of prematurity and stillbirth and has been invited speaker at the GAPPS International 

Conference on Prematurity and Stillbirth and March of Dimes/Burroughs Wellcome 

Meetings. CI-Salomon is a member of the Australian and New Zealand Placental Research 

Association, the International Society of Extracellular Vesicles, the Australasian Diabetes in 

Pregnancy Society and Society for Reproductive Investigation. CI-Salomon is a board 

member of the International Federation of Placenta Association and an editorial board 

member of The Journal of Reproductive Medicine, Gynaecology & Obstetrics. The 

UQCCR-based team will work closely with their UQ colleague, CI-Trau, Professor Matt 

Trau is currently a Professor of Chemistry at The University of Queensland (UQ) and 

Deputy Director and co-founder of the Australian Institute for Bioengineering and 

Page 13



Nanotechnology. Prof Trau’s expertise are in nanobiotechnology, materials science, 

biomarkers, diagnostics, and personalised medicine. Matt’s involvement in the CRE is 

crucial to the development and application of new and innovative technologies in obstetrics 

medicine. 

2.5.2 Screening for early identification of PE will be championed by CI-Hyett. In addition to the 

largest public obstetric screening service in Australia that CI-Hyett runs, he will progress 

uptake through his professional network that includes his membership of the British Royal 

College of Obstetricians & Gynaecologists and NSW Commission Maternal and perinatal 

RCA Review Committee. CI-Hyett is Deputy Chair of Royal Australian and NZ college of 

Obstetricians & Gynaecologists, Education Subcommittee chair of the International Society 

in Obstetrics and Gynaecology, member of the Australian Pre-eclampsia Research Network 

and the Impact group that co-ordinates multi-centre RCTs in Australia and New Zealand 

Board member of Fetal Medicine Foundation, (UK) and member of the New Zealand 

Ministry of Health Down's syndrome screening technical support group. CI-Hyett is 

regularly invited to speak to international perinatal societies and has addressed International 

Federations of Placental Associations’ World congress in Fetal Medicine 

2.5.3 Screening for early identification of GDM will be championed by CIs-McIntyre and 

Simmons who have worked together for over 15 years. CI’s-McIntyre and Simmons hold 

honorary/ordinary membership of Diabetes in Pregnancy Study Group of the European 

Association for the study of Diabetes and are members of Australian Diabetes Society, 

Australasian Diabetes in Pregnancy Society, and American Diabetes Association, CI 

McIntyre is also a member of Society for Obstetric Medicine Australia and New Zealand 

and FIGO (International Federation of Gynaecology and Obstetrics), and CI Simmons is a 

member of the European Association for the study of Diabetes and Diabetes UK. Both of 

these CI’s have been president of the Australasian Diabetes in Pregnancy Society and Co- 

Chaired the [Australian] National Diabetes in Pregnancy Advisory Committee. CI McIntyre 

also maintains clinical involvement as Director of Obstetric Medicine at Mater Health 

Services and Head of the Mater Clinical School of the University of Queensland. Professor 

McIntyre is currently the Chair of the International Association of Diabetes in Pregnancy 

Study Groups (IADPSG). Through these networks CI-McIntyre has a track record of having 

contributed to the definition of priorities for the care of women with diabetes before, during 

and after pregnancy. CI-Simmons maintains clinical involvement as Head of the 

Campbelltown Hospital adult, paediatric and surgical endocrinology services, Chair of the 

Campbelltown Hospital Clinical Council and Chair of the Campbelltown Hospital Research 

Committee. CI-Simmons was also Co-Chair, NZ National GDM Working Group (2006); 

Diabetes UK Health Professional Education Chair (2010-2014); member, Mid Essex 

Clinical Commissioning Group (2013-2014); Deputy Divisional Director, Division of 

Medicine, CUH (2011-2014). While in Cambridge, besides being diabetes clinical lead, he 

was involved in the local diabetes network chairing the referral pathways and IT working 

groups. He has provided key data on the epidemiology of diabetes in the UK, Australia 

(including as a member of The Australian and NZ Diabetes and Cancer Collaboration) and 

New Zealand with studies of up to 100,000 participants, which continue to be used as source 

data in policy documents. 

2.5.4 Screening tests that contribute to the implementation of precision medicine in obstetrics to 

improve pregnancy and neonatal outcome will be championed by CIs-Colditz and Kumar. 

CI-Colditz is a practising neonatologist and his intellectual leadership is recognised at local, 

state and national levels: e.g. Chair QLD Clinician Scientists Assoc., senior roles in the 

Division of Paediatrics and Child Health within the Royal Australasian College of 

Physicians (President-elect, Chair of Research Committee, member of Council, member of 

Executive) as well as in the Royal Australasian College of Physicians (Chair, Research 

Page 14



Committee, Director/board member RACP), member QLD Maternal and Perinatal Quality 

Council, Chair QLD Congenital Malformations Committee, and Leader State Clinical 

Guideline on Neonatal Seizures. CI-Kumar’s professional networks have already been 

identified as critical to his profile. In 2010/2011, the Times newspaper undertook an exercise 

to identify Britain's leading specialists based on information from professional bodies. Prof 

Kumar was one of only 2 fetal medicine specialists on this list. 

2.5.5 Embryo screening for the steadily rising Assisted Reproductive Technologies (ART) will be 

championed by CI-Homer. He is a practising fertility specialist and is the only such 

specialist in Australia who also conducts internationally-leading basic science research in 

reproductive biology thereby straddling key elements of the translational pipeline. He 

oversees a fully equipped laboratory for oocyte and embryo research at UQCCR, the first of 

its kind in Queensland. CI-Homer will be able to use his affiliations to the Royal Australian 

and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) and Fertility 

Society of Australia (FSA), their UK counterparts The Royal College of Obstetricians and 

Gynaecologists (RCOG) and British Fertility Service (BFS). At a more advanced stage of 

early screening implementation, CI-Homer will work networks within the European Society 

of Human Reproduction and Embryology (ESHRE) and the American Society of 

Reproductive Medicine (ASRM). 

3. Develop the health and medical research workforce by providing opportunity to advance 

the training of new researchers, particularly those with a capacity for independent 

research and future leadership roles 

Quality Research: A central and underpinning principle that distinguishes this CRE and delivers 

unique opportunities for advanced training is the implementation of an industry-standard quality 

management system (QMS) across the entire enterprise. Common to all QMS, is a process of 

continuing review and improvement. Quality Management Unit is an essential component of any 

successful QMS. As such, the CRE will establish a research Quality Management Unit to provide 

independent oversight of the operational and governance activities of the CRE. This will also 

provide a new career pathway for the research workforce in Australia, training and leadership 

development. 

Leadership Development: During the first five years, the CRE team will leverage its collaborative 

network to develop the future leaders in obstetric clinical practice and research in Australia. The 

CRE team includes expertise for investigating the basic biology of gametes and embryos thereby 

extending their reach to the prenatal stages, providing a unique opportunity for training in this niche 

area of rapidly growing significance due to the increasing uptake of ART. This will be achieved by 

mentoring trainees and providing unique opportunities for career development with the structure of 

the CRE. In particular, the CRE will actively promote the development and advancement of 

women to leadership positions within obstetric medicine and clinical research. To further reinforce 

the CRE’s commitment to leadership development of women in obstetrics, an award will be made at 

the CRE’s research workshop and community lecture series for Excellence in Obstetrics Research 

Translation. The CIs have an outstanding track record in mentoring and supervising research 

higher degree students, post-doctoral and clinical fellows. 

International industry standard training: The CRE provides a unique translational research 

training environment in Australia for clinicians and research scientists. Over the past four years CIs 

have established a clinical diagnostic facility within The University of Queensland Centre for 

Clinical Research that is NATA accredited. At the core of this facility is an industry standard 

research quality management system (ISO17025 and ISO13485). The significance of this 

accreditation is that clinical research conducted within this environment is regulator-ready. That is, 

Page 15



it complies with requirements of the FDA and TGA for regulatory approval. Thus, the time and 

cost from research to implementation is significantly reduced. 

Recent studies identify that one of the major barriers for the translation of academic research 

into clinical application is the inability of data to be replicated within industry standard 

environments. 42 The lack of research quality management systems and appropriate design control 

is a significant factor contributing to this failure. The research quality management systems 

developed over the past four years will encompass all activities conducted within the CRE. The 

CRE, thus, will function as an education and training platform in research quality management 

systems and the implementation of international industry standards in clinical research. Research 

conducted within its environment will align with industry and clinical practice and, therefore, 

facilitate its translation implementation. The CRE will be a national hub for training the next 

generation of industry-standard researchers and practitioners. 

To further promote the development of future clinical researchers and clinicians in obstetrics 

medicine the CRE will provide 5 PhD scholarship for exceptional PhD / MD PhD students (3 

national, 2 international). CRE team members will also develop and provide advanced training 

programs in research governance and compliance with industry standards and models of integrated 

pregnancy care. Annually, the CRE team will conduct a research workshop to review outcomes. In 

conjunction with the annual workshop, a public lecture series will be presented as a key community 

and end-user engagement activity. In addition, end-users will also engage via the CRE’s website 

and Facebook initiatives. 

Best Practice Integrated Pregnancy Care Service: In addition to the training and development 

opportunities identified above and to provide effective and immediate translation of the research 

outcomes of the CRE and a substantive platform for the development of the health and medical 

research workforce the CRE will establish an integrated pregnancy care service. BIPS will function 

as an iconic clinical unit for advanced training and practice for both clinical and scientific 

practitioners and students. BIPS will leverage the extensive expertise and experience of the CRE 

CIs and enhance transitional potential. It will deliver in-clinic outcome data necessary for uptake 

by end-users. Through the establishment of BIPS, a whole of pregnancy precision medicine-based 

management strategy will be implemented and will provide a unique clinical training environment. 

4. Facilitate collaboration 

CRE team members already have a strong existing collaboration and evidence of working together 

effectively (aspects of which have already been detailed in Section 2.5 of this application). Over 

the past 6 years, a strong, collaborative network can be evidenced between team members within 

the UQCCR viz Mitchell, Rice, Salomon, Colditz, Duncombe, Dekker, Callaway, Whiley and 

Homer. The QGF collaboration has been in place for 2 years; successfully providing clinical 

samples and resulting abstract and review publications. Colditz, Kumar and Callaway have a longstanding 

collaborative and professional engagement through the royal Brisbane and Women’s 

Hospital. McIntyre and Simmons have worked together for more than 15 years. A collaboration 

between AIBN and UQCCR has developed over the past 2 years and more recently between 

Rowan, Trau and Rice. While this later collaboration is still formative significant opportunity has 

been identified through this CRE, including the placement of AIBN research personnel within the 

NATA accredited facility within UQCCR to translate technological developments into clinical 

application; the conjoint appointment of a level B/C biomarker discovery and development research 

between the organisations; and the provision of PhD scholarship top-up to further promote 

collaborative engagement. These joint initiatives will generate new research capability, promote the 

Page 16



integration of preclinical and clinical research activities across the network; and enhance mentoring 

and career development opportunities. 

In the next five years, this CRE will be an international hub for: innovation in personalised 

reproductive medicine; the conduct of end-user oriented research and development activities to 

international industry standards; the delivery of Level 1 and 2 evidence that will inform clinical 

decision making through the implementation of precision medicine; excellence in clinical and 

research training; research quality management systems; biomarker discovery and the development, 

validation and implementation of In Vitro Diagnostics; translation of nanotechnology into 

personalised medicine (see Figure below). The CRE will enhance the capacity of its members, 

trainees and students to further develop collaborations; across the multiple disciplines within the 

CRE; within Australia and internationally. 

The CRE research will be conducted within three integrated capacities for which the CIs and AIs 

bring the necessary multidisciplinary expertise. Key elements of these capacities are already 

operational and support ongoing projects between the CIs and AIs. 

The core capacities of the CRE will provide advanced training, to international industry standard 

and within a research quality management system, for clinical trainees, post-doctoral fellows and 

research higher degree students as well as professional research and quality assurance staff. As the 

capacities are integrated in all projects they enhance collaborative engagement between CIs and AIs 

throughout the CRE. This collaboration is further facilitated by the current utilisation of 21 CFR 

part 11 compliant and NATA accredited cloud-based electronic notebooks and clinical sample 

tracking systems that are currently used by core members and that will be rolled out across the 

CRE. This system provides an instantaneous means of data sharing across the globe. 

The CRE will benefit from financial leveraging and industry engagement. The University of 

Queensland, and the Faculty of Medicine and the Faculty of Medicine will support the CRE with 

$50,000 annually. AIBN has committed to funding a PhD student in medical device development 

and precision medicine ($25,000 pa). Shimadzu Austrlaia has committed to funding a PhD student 

($27,000 pa) to work on MS-based biomarker discovery and to $30,000 in equipment upgrades to 

Page 17



enhance the capacity of the CRE. To further promote the development of future leaders, the CRE 

will provide five PhD top-up scholarships to exceptional RHD students with clear leadership 

potential. 

Building the Translational Pipeline: A strong, long-term multidisciplinary collaborative network 

has already been established between CRE CIs and AIs that spans multiple national and 

international organisation. This network provides opportunity for intellectual exchange and the 

enhancement of the interface between technological advances and patient care. 

For example, this CRE will establish a translational pipeline between technology and application 

intensive facilities (e.g. AIBN) and clinical practice. This will be achieved by the placement of 

research staff and students into clinical development environments (e.g. UQCCR) and their direct 

engagement with clinical practice in Australian and internationally. New technological 

achievement thus can be aligned with clinical and patient needs. 

Building National and International Collaborations: The CIs are well positioned to leverage their 

existing national and international collaboration to further advance the research and training 

objective of the CRE. In particular, UQ CIs have extremely productive collaborative clinical 

research and MD and PhD training programs with the Ochsner Health System in New Orleans (the 

largest provider of health care services in Louisiana). A similar partnership has been established 

with one of the largest private hospital networks in Chile through Clinica Davila, Santiago, Chile. 

Such partnerships provide opportunity to expand collaborative engagement between the members of 

the CRE and advancement of clinical and scientific enterprise. 

5. Record of research and translation achievement – relative to opportunity 

The CRE comes complete with a built-in capacity to translate its developments and these will 

represent the lasting legacy of the endeavour. The CI and AI team members each have outstanding 

records acquired on an international stage, of translating their research into practice within the very 

field addressed by the CRE. Past successes demonstrate a capacity to navigate and inject value to 

the service chain of delivery within healthcare systems. 

These are summarized in the attached table: 

CI 

Rice 

Simmons 

RECORD OF TRANSLATION IN FIELD 

More than a decade of experience within the biotechnology sector (both private 

and public) in the development, evaluation and implementation of diagnostics 

tests. 

Conducted phase 2 and 3 biomarker trials to evaluate the clinical utility of an 

early detection, blood based diagnostic. 

Industry experience includes being co-founder of biotechnology company 

HealthLinx, (HTX, 2003), Executive Director (2006), General Manager Science 

and Operations (2007) and Chairman (2008-2013). This company listed on the 

ASX in 2006 as a diagnostic company that focuses on the development and 

delivery of in vitro diagnostics and multivariate index assays. 

Service as a member of Clinical and Scientific Advisory Committees of ASXlisted 

companies and as a member of the Technical and Regulatory Standing 

Committee of IVD Australia (2010-2012). 

Closely involved in the translation of clinical research findings into clinical 

practice, in particular through the redefinition of gestational diabetes (member of 

the WHO working group), establishment/redesign of pre-pregnancy and 

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McIntyre 

Kumar 

Trau 

Mitchell 

pregnancy services in Australia, New Zealand and UK. 

Established diabetes peer support across an English county, taken up by Diabetes 

UK across a further 5 counties (type 2 together)-training and other components 

now embedded in diabetes UK operations 

Developed and evaluated diabetes integrated care approach now in place in in 

parts of Cambridgeshire 

Part of team that developed/introduced RCT of school based intervention to 

reduce childhood obesity in the Waikato, NZ-now continued and extended 

beyond Waikato 

Study of random blood glucose screening for GDM at booking - now used by 

many services around the world 

Regional study of a systems approach to pre-pregnancy planning in T1/T2 

diabetes in a number of centres in East Anglia, now extended across more 

Hospitals 

Closely involved in the translation of clinical research findings into clinical 

practice, in particular through the redefinition of gestational diabetes and 

promotion of optimal diagnosis and treatment of this common pregnancy 

complication. 

Development of guidelines including most notably: 

Queensland Clinical Guidelines Translating evidence into best clinical practice 

GDM 

Local GDM implementation 

International (FIGO) guidelines 

Updating of guidelines in the light of new evidence 

Contributed to the most recent set of guidelines put out by the Fetal & Neonatal 

Transfusion sub-committee of the British Committee for Standards in 

Haematology (BCSH). 

Co-author of an RCOG guideline pertaining to the management of women with 

red cell antibodies in pregnancy. These guidelines influence and guide practice in 

many different countries. 

Specialist advice to the National Institute of Clinical Excellence for Fetal 

Medicine 

Interventional procedures and review of fetal medicine guidelines prior to 

publication 

Clinical advisor to the Healthcare Commission 

Developed nanoscale biosensors as a strategy for disease management 

Developed single drop DNA test with capacity to revolutionise the detection of 

diseases 

Initiated and led collaboration between leading nanotechnologists, molecular 

biologists, geneticists and commercial researchers with the goal of creating 

cutting edge diagnostics. 

Member Medicine and Public Health Panel (2012) for the Performance Based 

Research Fund that reviewed “quality” measures for all University Researchers 

in New Zealand (1,000). 

Reviewer for three Tommy’s research centres in the United Kingdom to 

determine their progress and whether the Campaign would continue funding 

them. 

Reviewer applications for the Preterm Labour Centre funded by Harris 

Wellbeing, UK 

Discovered true cause of Pre-term labour (Discovery in collaboration with Dr 

Roberto Romero) 

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Advisor to Adeza Biomedical for Fetal Fibronectin Testing Development which 

remains the only FDA approved diagnostic for preterm labour. 

Hyett Internationally recognized for describing the underlying pathophysiology of 

increased nuchal translucency, a marker for aneuploidy and cardiac defects that 

forms a central part of the 12 week ultrasound scan. This scan is now a routine 

part of pregnancy care and the work underpins significant improvement in early 

diagnosis of fetuses affected by chromosomal or cardiac abnormalities. 

Member of the team that developed endoscopic laser ablation of the placental 

circulation that is now recognized as the key intervention for improving survival 

in affected twin pregnancies from 5% to 85%. 

Recognized internationally for his leadership in bringing cell free fetal DNA 

technologies to clinical practice in both RhD and aneuploidy screening. 

Homer Established an internationally recognised research programme focused on 

understanding mammalian oocyte maturation and oocyte quality and their impact 

on female reproductive health. 

Jointly set up and co-directed UNSW’s first Oocyte Biology Research 

Laboratory 

Established UQ’s first Oocyte Biology Lab located within UQ’s Centre for 

Clinical Research. 

Co-founder and director of Jumpstart Fertility Pty Ltd a company that is in the 

process of obtaining strategic investments from the NASDAQ listed company, 

Ovascience. 

Colditz Established a multidisciplinary, productive, collaborative, national and 

international network with paediatricians, neuroscientists, engineers, 

psychologists and obstetricians. 

Holds an Australian patent (2006 Approved 2006906381) for a method for 

detecting EEG seizures in a newborn. 

Possesses knowledge base relevant to commercialization and the application of 

research to clinical practice and health policy. 

Has undertaken key research that defines Clinical Practise in fetal monitoring and 

is author on several Cochrane reviews. 

Salomon Established and lead the UQCCR Exosome Biology Laboratory that conforms 

the ISO standards (ISO17025 and 13485) 

Established the mechanism of vascular dysfunction in the feto-placental 

circulation in GDM and the role of the insulin receptor isoform in this 

phenomenon. These results were the baseline to identify whether known 

vasoactive molecules whose plasma levels are elevated in the fetal blood in GDM 

pregnancies, play a functional role in the altered vascular reactivity and 

endothelial dysfunction in women who develop GDM. 

Several contributions to our understanding the role of placental exosomes during 

gestation, and my work demonstrated their nature as specific subcellular 

compartments and their ability to modify the biological function of target cells 

(maternal and/or fetal cells). 

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CI Track Record including top five publications in the last five years per CI) 

CI A TRACK RECORD: Prof Gregory Rice, PhD, Grad Dip MGT MAH, BSc (Hons) 

Career summary (selected qualifications, employment and appointment history) 

2010- NHMRC Principal Research Fellow, UQ Centre for Clinical Research 

2010-2015 Deputy Director (Translation), UQ Centre for Clinical Research 

2011-2015 Member, Centre Confirmation and Promotion Committee, UQ 

2011-2015 Member, Research Higher Degree Committee, Faculty of Health Science, UQ 

2010-2014 Director and Chairman, National Centre for Health Innovation Limited 

2010-2013 Member, Technical and Regulatory Standing Committee of IVD Australia. 

2008-2013 Chairman, HealthLinx Limited 

Honours and Awards 

2015 Senior Clinical Researcher, Ochsner Medical Foundation, New Orleans, LA, USA 

2012 Honorary Professor, University of the Andes, Santiago, Chile. 

2012 Honorary Member, Chilean Society of Ultrasound and Medical Biology 

Research Support (last 5 years (selected) 

2014-16 MECESUP Ministry of Education, Chile, $4,690,000 

2014-15 ARC Discovery $300,000 

2011-2014 SuperScience Translating Health Discovery, $6,700,00 

2014 CORFO Chilean Economic Development Agency, $335,953 

2010-2014 NHMRC Principal Research Fellowship $677,500 

2009-2011 NHMRC Project Grant #526686, $426,600, 

2009-2011 NHMRC Project Grant #546016 $528,750 

2008-2010 NHMRC Project Grant #509127 $461,625, 

Contribution to the field of research (selected) 

2014 Invited Speaker, “Preeclampsia: novel biomarkers and mediators” 46 th International 

Congress on Pathophysiology of Pregnancy, Tokyo, Sept 18-20. 

2013 Keynote Speaker “The Business of Biomarkers” AGM National Product Liability 

Association, Melbourne September 28 th . 

2013 Invited Speaker “Inflammation processes, oxidative stress and angiogenic factors in 

preeclampsia”. 45th International Meeting of Gestosis Organization, 6-8 December 

2013, Athens Greece. 

2013 Invited Speaker, “Exosomes - Nanomedicine Applications in Obstetrics and 

Gynaecology” Singapore International Congress of Obstetrics and Gynaecology, 

Singapore (22-24 August). 

2013 Invited Speaker, “The role of exosomes in the development of placental 

complications SLIMP (Latin American Symposium on Maternal Fetal Interaction 

& Placenta), Brazil (Feb 17 th , 2013). 

2012 Plenary Speaker “Molecular Biology in Routine Clinical Practice” IX Congress of 

the Sociedad Chilean de Ultrasonografia en Medicina Y Biologia, Vina del Mar, 

Chile June 7-9 th . 

Patents - 

WO2004019009 A1 currently licensed to Sigma Aldrich 

Collaborations - International - University of the Andes and Catholic University of Chile, Santiago 

(6 grants awarded > $5 million. 4 reviews, 4 papers); National: QUT two NHMRC 

Project grants submitted this round. 

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Community engagement and participation - Chairman, National Centre for Health Innovation 

Professional Involvement (selected) 

2010-2012 Immediate Past President, International Federation of Placenta Associations 

2007-2009 President, International Federation of Placenta Associations 

2012-present Member, Editorial Board, Open Journal of Obstetrics and Gynecology 

2012- present Member, Editorial Board, Conference Papers in Biology 

2011-present Member, Editorial Board, Scientifica 

Supervision and Mentoring (last 5 year) Honours 8 (1 current); MSc 1(1); PhD 4 (3) 

Peer Recognition and Service last 5 year (selected): 

2013 NHMRC Grant Review Committee 

2012 NHMRC Research Translation Faculty 

2012 NHMRC Grant Review Committee 

2011 NHMRC Fellowship Review Committee 

Other contributions to NHMRC 

2014 NHMRC Assigner Academy 

Top 5 Publication in the last 5 years 

1. Sarker S, Scholz-Romero K, Perez ,. Illanes SE, Mitchell MD, Rice GE , Salomon C. 

Placenta-derived exosomes continuously increase in maternal circulation over the first 

trimester of pregnancy. Journal of Translational Medicine. (2014) 12:204 

doi:10.1186/1479-5876-12-204 

2. Salomon C, Torres MJ, Kobayashi M, Scholz K, Sobrevia L, Sobrevia L, Dobierzewska A, 

Illanes SE, Mitchell MD, Rice GE (2014) Pregnancy-Associated Changes in Placenta- 

Derived Exosome Concentration and Bioactivity in Maternal Plasma. PLoS One. DOI: 

10.1371/journal.pone.0098667 

3. Kobayashi M, Salomon C, Tapia J, Illanes, SE, Mitchell MD, Rice GE (2014) Ovarian 

cancer cell invasiveness is associated with discordant exosomal sequestration of Let-7 

miRNA and miR-200. Journal of Translational Medicine. 12:4. doi:10.1186/1479-5876-12-4 

These 3 papers establish leadership in exosome biology and analysis applied to placental 

development. In particular, through the work of Dr Salomon (a post-doctoral fellow in my 

group) and Ms Kobayashi (a PhD student in my group), we have improved the “bestpractice” 

protocol for isolating exosomes and begun to characterise the factors that regulate 

exosome protein and miRNA content, and their effects on target cells. 

4. Peiris HN, Ashman C, Vaswani K, Kvaskoff D, Rice GE, Mitchell MD (2014) Method 

Development for the Detection of Human Myostatin by High-Resolution and Targeted Mass 

Spectrometry. J Clin. Endocrinol Metab doi: 10.1210/jc.2014-2615 This paper establishes 

our expertise in developing and applying mass spectrometry approaches. 

5. Rice GE, Scholz-Romero K, Sweeney E, Peiris H, Kobayashi M, Duncombe G, Mitchell 

MD, Salomon C. (2015) The Effect of Glucose on the Release and Bioactivity of Exosome 

from First Trimester Trophoblast Cells. J Clin Endocrinol Metab. 2015 Aug 4:jc20152270. 

[Epub ahead of print] PMID:26241326 This paper delivers proof-of-concept of the 

involvement of exosomes in glucose homeostatis 

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CI B TRACK RECORD: Prof Paul Colditz 

Career summary Prof. Colditz is a practicing neonatologist with a DPhil in Medicine from the 

University of Oxford, UK. He is currently and for the past 20 years has been Director of the 

Perinatal Research Centre, one of the largest research centres in the School of Medicine and since 

2012 also Deputy Director University of Queensland Centre for Clinical Research (UQCCR). His 

research focuses on clinically important perinatal health problems and translation to clinical 

practice. It focuses on brain injury, neuroprotection and pathways to improving neurodevelopmental 

outcomes. 

Qualifications and dates of award/conferment 

Institution And Location Degree 

• Australian Institute Company Directors GAICD 2015 Business 

• Royal College of Paediatrics and Child Health FRCPCH 1997Medicine 

• University of Oxford DPhil 1988 Medicine 

• University of New South Wales, MBiomedE 1985 Engineering 

• Royal Australasian College of Physicians FRACP 1984 Medicine 

• University of New South Wales MBBS 1977 Medicine 

Contribution To The Field/Impact (include translation of research into health outcomes) 

Prof Colditz has been a lead CI on a number of perinatal randomized controlled trials where the 

measurement of infant outcomes has been a major component. He was responsible for the 

acquisition of the southern hemisphere’s first neonatal MRI compatible incubator as an indicator of 

his interests in accurate determination of outcomes. He has established a multidisciplinary, 

productive, collaborative, national and international network with paediatricians, neuroscientists, 

engineers, psychologists and obstetricians. CI Colditz has been granted over AUD$50m in project, 

equipment and fellowship funding for research, including being CI on 19 NHMRC grants, an 

NHMRC Practitioner Fellowship, 3 ARC grants and 6 International grants. Prof Colditz’s research 

group is recognized both nationally and internationally. He has received recognition in both a 

clinical context (Distinguished Research Medal for Research Excellence (2012) from the Royal 

Brisbane and Women’s Hospital) and academic context (recipient of University of Queensland of a 

‘Top 10’ Q Index Award). 

Patents 

He holds an Australian patent (2006 Approved 2006906381) for a method for detecting EEG 

seizures in a newborn. 

Collaborations 

Prof Colditz collaborates with the QLD Cerebral Palsy Research Centre; Children’s Nutrition 

Research Centre, UQ; the Uni. of Adelaide; Uni. of Sydney; Uni. of Melbourne; Uni. of Cork, and 

Uni. of Helsinki. He has an ongoing successful collaboration with the Uni. of Qatar, resulting grants 

>$9M in the last 5 years. 

Community Engagement & Participation 

Prof Colditz has a long standing involvement in supporting health consumer and advocacy 

organisations. He is currently a board member of the national SIDS & Kids Foundation. He has 

been awarded the Ray Phippard Award for services to medical research by the Lions Medical 

Research Foundation. In 2013 he was awarded life membership of SIDS & Kids (QLD). 

Professional Involvement (include committee membership, conference organisation and other 

service level participation) 

Page 23



CI Colditz’s intellectual leadership is recognised at local, state and national levels: e.g. Chair QLD 

Clinician Scientists Assoc., senior roles in the Division of Paediatrics and Child Health within the 

Royal Australasian College of Physicians (President-elect, Chair of Research Committee, member 

of Council, member of Executive) as well as in the Royal Australasian College of Physicians 

(Chair, Research Committee, Director/board member RACP), member QLD Maternal and Perinatal 

Quality Council, Chair QLD Congenital Malformations Committee, and Leader State Clinical 

Guideline on Neonatal Seizures. His experience in knowledge application includes 

commercialization and the application of research knowledge to clinical practice and health policy. 

CI Colditz is current lead on QLD Health Clinical Practice Guideline for neonatal seizures and 

member of perinatal Clinical Practice Guidelines (CPG). 

Supervision & Mentoring 

Professor Colditz has 14 current PhDs in the fields of basic science, engineering, medicine and 

allied health and has supervised 33 to completion. He has 6 current Postdoctoral fellows. CI Colditz 

supervises RHD students across medicine, nursing, allied health, engineering and maths/physics 

from Vietnam, China, Iran, Malaysia, Indonesia, Singapore, UK, US, Holland, Germany. 

Peer Review Involvement (include NHMRC, other granting organisations, manuscripts, editorial 

responsibilities) 

CI Colditz has been a member, including chair, of NHMRC project and program grant review 

panels regularly for more than a decade. He has been a member of NHMRC Australia Fellowship 

panel and for the past two years a member of a Career Development Fellowship Panel and for 2016 

a member of the Project Grant panel. In 2016 CI Colditz was on the scientific review team for the 

Cerebral Palsy Alliance Research Foundation Grants Program and SIDS and Kids. He has been a 

peer reviewer for more than a dozen journals in recent years. 

Other Relevant Information 

Professor Colditz has published > 200 peer-reviewed publications (65 in the past 5 years), over 600 

conference abstract/proceedings, 3 books and 6 book chapters. 

TOP 5 PUBLICATIONS OVER THE LAST 5 YEARS (include reasons why these publications 

have been selected) 

1. Doyle L, Anderson P, Haslam R, Lee K, Crowther C, Australasian Collaborative Trial of 

Magnesium Sulphate (ACTOMgSO4). School age outcomes of very preterm infants after 

antenatal treatment with magnesium sulfate vs placebo. JAMA. 2014; 312(11):1105-1113. 

2. Pannek K, Guzzetta A, Colditz PB, Rose S. Diffusion MRI of the neonate brain: acquisition, 

processing and analysis techniques. Pediatric Radiology 2012 42;10: 1169-82. 

3. Pannek K, Hatzigeorgiou X, Colditz PB, Rose S. Assessment of structural connectivity in the 

preterm brain at term equivalent age using diffusion MRI and T2 relaxometry: a networkbased 

analysis. PLoS One 2013 8;8: e68593. 

4. Collins CT, Gibson RA, Anderson PJ, McPhee AJ, Sullivan TR, Gould JF, Ryan P, Doyle 

LW, Davis PG, McMichael JE, French NP, Colditz PB, Simmer K, Morris SA, Makrides M. 

Neurodevelopmental outcomes at 7 years’ corrected age in preterm infants who were fed 

high-dose docosahexaenoic acid to term equivalent: a follow-up of a randomised controlled 

trial. BMJ Open. 2015 Mar 18;5(3):e007314. doi: 10.1136/bmjopen-2014-007314. 

5. Jacobs SE, Morley CJ, Inder TE, Stewart MJ, Smith KR, McNamara PJ, Wright IM, 

Kirpalani HM, Darlow BA, Doyle LW, Colditz PB (Infant Cooling Collaboration). Wholebody 

hypothermia for term and near-term newborns with hypoxic-ischemic encephalopathy: a 

randomized controlled trial. Arch Pediatr Adolesc Med. 2011; 165: 692-700. 

Page 24



CIC: Professor Hayden Homer (MBBS, PhD, MRCOG, CCSST [RCOG, UK], FRANZCOG) 

Career Summary: In January 2016, CIC Homer relocated to UQ to take up the fully endowed 

Christopher Chen Chair in Reproductive Medicine. Prior to that CIC Homer relocated from the UK 

to Australia in January 2014 after being recruited to UNSW through their Strategic Priority Funding 

route. Hayden has been dually accredited as a Specialist in Obstetrics & Gynaecology and a 

Subspecialist in Reproductive Medicine & Surgery through the British Royal College of 

Obstetricians & Gynaecologists (2012). CIA Homer was previously Clinical Senior Lecturer and 

Honorary Consultant in Reproductive Medicine at one of the world’s leading universities, 

University College London (UCL). Since moving to Australia he has also been elevated to Fellow 

of the Royal Australian and New Zealand College of Obstetricians & Gynaecologists (2014). 

Alongside clinical work, Hayden has established an internationally recognised research programme 

focused on understanding mammalian oocyte maturation and oocyte quality and their impact on 

female reproductive health. Hayden is 7 years post-PhD and is one of only a handful of basic 

science researchers in reproductive biology who is also clinically qualified and subspecialty trained 

in Reproductive Medicine. Since relocating from the UK, Hayden jointly set up and co-directed 

UNSW’s first Oocyte Biology Research Lab and more recently has established UQ’s first Oocyte 

Biology Lab located within UQ’s Centre for Clinical Research. In this time as well, CIA Homer 

completed equivalence requirements for Australian clinical registration and gained familiarity with 

clinical practice as a Staff Specialist in Gynaecology and Infertility. CIC Homer is 7 years post-PhD 

and although the last 3 years have been periods of major readjustment, he has successfully secured 

over $1.5 M dollars in NHMRC research funding and established highly productive research 

collaborations. 

Contribution to Field of Research, International and National Profile: 

Although only 7 years post-PhD, CIC Homer has placed leading papers in his field including 2 

high-impact senior author papers in the past 5 years (Developmental Cell and Development). In 

2013, he was invited editor for a prominent research protocols handbook on mammalian oocytes 

(Methods in Molecular Biology series) with 20 chapters from world-leading oocyte research labs. 

CIC Homer has also published landmark papers in the journals, Science (Homer et al. 2009) and 

Genes & Development (Homer et al. 2005) that were both cited by the Faculty of 1000 Biology for 

defining key regulatory facets in oocytes and are some of the most highly cited works in the field. 

In the last 5 years Hayden has had 12 invited contributions to various books and journals. He has 

been invited speaker at several international and national meetings including meetings of the 

Australian Society of Reproductive Biology (2014, 2016), the Fertility Society of Australia Annual 

Meeting (2013, 2015), Scientists in Reproductive Technology (2016) and Frontiers in Reproductive 

Medicine (2015) at Washington, USA. 

Research Funding: 

During his time in Australia (2014-2016), Hayden has received over $1.5 M funding as CIA 

including NHMRC Project (x2) and Development Grants (x1) for oocyte- and fertility-related 

research (APP1078134, $515,615, APP1103689, $410,983 and APP1122484, $445,827) and a 

Ramaciotti Establishment Grant ($75,000). Hayden is also CIA on two Equipment Grants, one from 

the NHMRC for a NanoString nCounter System (GNT9000249, $366,500) and the other from 

UNSW for an Oocyte Microinjection System ($56,000). He is Co-CI on two further Equipment 

Grants at UNSW (see below). Hayden’s PhD student, Dave Listijono, recently secured an NHMRC 

Postgraduate Scholarship (APP1114631, 2016, $71,791.50) and won the Oozoa Award at the 

Society for Reproductive Biology Annual Meeting (2015). Another of his students, Nicholas Loh, 

was a finalist in this year’s Oozoa Awards (2016). Within the past 5 years, prior to moving to 

Australia, Hayden’s research at UCL was funded by a highly prestigious Wellcome Trust Clinician 

Scientist Fellowship ($1.26 million; 2007-2013), which was one of only two to have ever been 

awarded to Reproductive Medicine. 

Page 25



Collaborations: 

Hayden was Principal Investigator in UCL’s world-leading Cross-Faculty Mammalian Oocyte & 

Embryo Research Laboratory (2007-2013). Since moving to Australia he has established productive 

collaborations with Professor David Sinclair, an international expert in sirtuin and NAD + regulation 

and aging with whom he has had success in NHMRC grant funding (APP1103689, APP1122484). 

CIC Homer’s NHMRC Grant APP1078134 involves collaborations with senior fertility clinicians 

(Prof William Ledger [Head of School, UNSW] and A/Prof Peter Illingworth [Director, IVF- 

Australia] and leading scientists (A/Prof Gilchrist [NHMRC Senior Research Fellow] and Prof John 

Carroll [Dean and Head of School, Monash University]). He led a successful bid for UNSW’s first 

NanoString nCounter System involving 17 co-CIs. Hayden is also co-CI on 2 further successful 

Equipment Grants for a Zeiss Laser Micro-dissection System (2015, $392,000) and a Zeiss Light 

Sheet Microscope (2015, $565,000). Hayden previously co-directed UNSW’s oocyte research lab 

jointly with A/Prof Gilchrist. 

Supervision and mentoring: 

CIC Homer currently supervises 5 PhD students, one of whom is funded by an NHMRC 

Postgraduate Scholarships. Two further students will commence in 2016, one of whom is funded by 

an International Postgraduate Research Scholarship. 

Peer Review Involvement: 

CIC Homer has peer reviewed for high impact journals in the past 5 years including Nature Cell 

Biology, Nature Communications, Development, Journal of Cell Science and Journal of Molecular 

Cell Biology. In the past 5 years, he has been grant reviewer for NHMRC Project Grants (2013 [x1]; 

2014 [x3]; 2015 [x3]; 2016 [x3]), the UK’s MRC (Project and Program Grants) and the French 

National Research Agency and has been a PhD examiner (x2, University of Newcastle, NSW). 

Top 5 publications in the last 5 years: 

CIC Homer is 7 years post-PhD. Alongside clinical practice and twice relocating his lab, he has 2 

high-impact papers as senior author both cited by the Faculty of 1000 Biology (asterisked below). 

1. Gui L and Homer H*. (2012) Spindle assembly checkpoint signalling is uncoupled from 

chromosomal position in mouse oocytes. Development 139(11):1941-1946. 

New insight into why chromosome segregation remains so error-prone in oocytes despite 

possessing a spindle assembly checkpoint surveillance mechanism. 

2. Gui L and Homer H*. (2013) Hec1-dependent cyclin B2 stabilization regulates the G2-M 

transition and early prometaphase in mouse oocytes. Developmental Cell 25(1):43-54 

Novel roles for kinetochores in regulating the G2-M transition in oocytes and new co-operative 

roles for cyclin B1 and cyclin B2 in promoting cyclin-dependent kinase 1 activation. 

3. Riris S, Webster P and Homer H. (2014) Digital multiplexed mRNA analysis of functionally 

important genes in single human oocytes and correlation of changes in transcript levels with 

oocyte protein expression. Fertility and Sterility 101(3):857-864. 

First paper to apply powerful NanoString technology to analyzing human oocytes and to report 

multi-gene profiling in any single cell without pre-amplification. 

4. Riepsamen A, Wu LE, Lau L, Listijono D, Ledger W, Sinclair DA, Homer HA. (2015) 

Nicotinamide Impairs Entry intro and Exit from Meiosis I in Mouse Oocytes. PLoS ONE 

10(5): e0126194. doi:10.1371/journal.pone.0126194. 

This paper showed that oocyte maturation is severely impaired by the pan-sirtuin inhibitor 

nicotinamide pointing to the importance of the sirtuin family of deacetylases in oocyte quality. 

5. Homer H. (2013) The APC/C in female mammalian meiosis I. Reproduction 146(2): R61-71. 

Invited review in one of the leading specialist journals in the field covering recent 

developments in oocyte cell-cycle regulation. 

Page 26



CI D TRACK RECORD Prof Murray Mitchell 

Career summary – (last 5 years) 

2015- Professorial Research Fellow, University of Queensland Centre for Clinical Research 

2010 - 2015 Director, University of Queensland Centre for Clinical Research 

2003-2009 Deputy Director ( Co-Director 2008-2009) National Research Centre for Growth and 

Development, N.Z. 

Research funding last 5 years (selected) 

I have received significant infrastructure funding through Therapeutic Innovation Australia (TIA), 

(8.9m-3.4m for UQCCR), A Clinical Academic Fellowship from The Queensland Government 

($375,000), NZ Government funding for Epigenetic Studies in Dairy Cows ($3m - $408,000) to 

Murray D Mitchell and an ARC Discovery Grant ($300,000). I have also received over $1m for UQ 

infrastructure mainly next generation sequencing items (Hi Seq and Mi Seq). 


Our team has ongoing collaborations with investigators in Santiago, Chile, University of the Andes 

(Ilanes) and Catholic University of Chile (Sobrevia) (8 grants awarded >5m, 4 reviews, 4 papers – 

all jointly with Prof. G.E. Rice), Singapore (Choolani), Adelaide and several institutions in 

Brisbane. 

Committees – last 5 years 

I am a member on several hospital committees e.g. (Research Excellence and Academic Leadership, 

Royal Brisbane and Women’s Hospital) and Research Foundations (RBWH and Prince Charles 

Hospital). I have also served on many UQ committees through my position as Director,UQCCR 

Awards & commendations & leadership 

In 2012 I received an Award from the Society for Gynecologic Investigation (SGI) in recognition of 

outstanding organization for the 5th SGI International Summit “Prematurity and Stillbirth”: 

Antecedents, Mechanisms and Sequelae”. I developed the idea for this meeting, took it through the 

Society organization, my University organization and then presided over the meeting that attracted 

people from worldwide and opened the way for Perth to bid for a full meeting of the SGI in the near 

future. In 2009 I completed my second term on the SGI Council, having been their first 

International (non-North American) member. 

Presentations, plenary and invited lectures (selected)- last 5 years 

I have been invited to present regularly at International Meetings. In particular I have been invited 

to the GAPPS ‘International Conference on Prematurity and Stillbirth” in Seattle, 2009 and the 

March of Dimes/Burroughs Wellcome Meetings in 2010 and 2012 on Prematurity and Stillbirth. 

These meetings have been the major driving forces in organising global approaches to the issues of 

prematurity and stillbirth. I am invited to the next such meeting in Siena this year. I have also been 

invited to speak at the Perinatal Branch of NICHD in a special research lectureship. 

Supervision – last 5 years 

In the past 5 years I have supervised 5BSc (Hons), 1 MSc and 13 PhD students. Additionally I have 

mentored 3 postdoctoral Fellows, 3 MBBS Honours students and 1 Occupational Trainee from 

Universidad de Chile. My students have a 100% success rate in graduating with their degrees. 

Service – last 5 years 

I have received grants to review from the Wellcome Trust (UK) Programme, Canadian Institutes of 

Health Research, National Health and Medical Research Council (Australia) and Canadian 

Page 27



Institutes of Health Research (China-Canada Joint Health Research Initiative). Separately, I was 

again asked to be a panel member of the Tertiary Education Commission (New Zealand). I was on 

the Medicine and Public Health Panel (2012) for the Performance Based Research Fund that 

reviewed “quality” measures for all University Researchers in New Zealand (1,000). 

PERTINENT – LAST 5 YEARS 

During the past five years I have moved from Auckland, New Zealand, to Brisbane, Australia (UQ). 

In my position as Director, UQCCR I have established a significant research infrastructure. The 

developments of a NATA accredited Centre for Clinical Diagnostics and a Centre for Clinical 

Genomics have been a major advance. My grants have excellent research infrastructure particularly 

with regards to mass spectrometry and next generation sequencing. Although this time commitment 

has reduced my outputs somewhat I believe that it is has been more beneficial to the overall 

research community. 

Top 5 Publications in the last 5 years 

1. Logan, P.C., Ponnampalam, A.P., Steiner, M. and Mitchell, M.D. Effect of cyclic AMP and 

estrogen/progesterone on the transcription of DNA methyltransferases during decidualization of 

human endometrial stromal cells Molecular Human Reproduction 19 (5): 302-312, 2013. This 

study was one of the first to describe the regulation by steroids of the transcription of DNA 

methyltransferases. This opened the way for developing novel therapeutic approaches to 

regulating pathways governed by epigenetic mechanisms. 

2. Sarker S, Scholz-Romero K, Perez ,. Illanes SE, Mitchell MD, Rice GE , Salomon C. Placentaderived 

exosomes continuously increase in maternal circulation over the first trimester of 

pregnancy. Journal of Translational Medicine. (2014) 12:204 doi:10.1186/1479-5876-12-204 

3. Salomon C, Torres MJ, Kobayashi M, Scholz K, Sobrevia L, Sobrevia L, Dobierzewska A, 

Illanes SE, Mitchell MD, Rice GE (2014) Pregnancy-Associated Changes in Placenta-Derived 

Exosome Concentration and Bioactivity in Maternal Plasma. PLoS One. DOI: 

10.1371/journal.pone.0098667 

4. Kobayashi M, Salomon C, Tapia J, Illanes, SE, Mitchell MD, Rice GE (2014) Ovarian cancer 

cell invasiveness is associated with discordant exosomal sequestration of Let-7 miRNA and 

miR-200. Journal of Translational Medicine. 12:4. doi:10.1186/1479-5876-12 These 3 papers 

establish leadership in exosome biology and analysis applied to placental development. In 

particular, through the work of Dr Salomon (a post-doctoral fellow in my group) and Ms 

Kobayashi (a PhD student in my group), we have improved the “best-practice” protocol for 

isolating exosomes and begun to characterise the factors 

5. Peiris, H.N, Ashman, C., Vaswani, K., Kvaskoff, D., Rice, G.E., Mitchell, M.D. (2014) Method 

development for the detection of human myostatin by high-resolution and targeted mass 

spectrometry. Journal of Proteome Research, 13 8: 3802-3809. doi:10.1021/pr5004642. 

Evidences expertise in proteomics and biomarker isolation. 

Additional pertinent publications include: 

Rahnama, F.,Thompson, B.,Steiner, M.,Shafiei, F., Lobie, P. and Mitchell, M.D., Epigenetic 

regulation of e cadherin controls endometrial receptivity. Endocrinology 150: 1466-1472, 2009. 

This study was among the first to describe epigenetic regulation of a key reproductive mechanism 

and demonstrate specific effects on functional as well as biochemical end points. As such it has 

been highly cited (40 citations); and 

Perry, J.K., Lins, R.J., Lobie, P. and Mitchell, M.D Regulation of invasive growth: similar 

epigenetic mechanisms underpin tumour progression and implantation in human pregnancy. 

Clinical Science 118: 451-457, 2010. This study described the not only the data supporting 

epigenetic regulation of critical pathways in human implantation but also drew parallels with 

similar regulation in pathways associated with tumour progression. Limits and opportunities that 

arise from this comparison were described. 

Page 28



CI E TRACK RECORD: Prof Matt Trau, PhD 

1992 The University of Melbourne, Melbourne, Australia 

PhD in Physical Chemistry 

1987 The University of Sydney, Sydney, Australia 

B.Sc. (Hons) 1 st Class (University Medal) 

Academic research, clinical, professional and industrial experience relevant to this 

application. 

Matt Trau is currently a Professor of Chemistry and Director of the Centre for Personalised 

Nanomedicine at the University of Queensland in Brisbane, Australia. His research is dedicated 

towards developing innovative nano-diagnostics to help transform the healthcare system towards 

early detection and personalized treatment of disease, and also to help enable the emerging 

“Wellness Industry” which aims to dramatically extend high quality human life through a 

combination of innovative diagnostic technology and preventative measures. Among Matt’s other 

roles, he is also deputy director and co-founder of the Australian Institute for Bioengineering and 

Nanotechnology (AIBN). Since graduating from the University of Sydney (BSc Hons I, University 

Medal) and the University of Melbourne (PhD in Physical Chemistry, 1993), he has held positions 

within industry and academia across the globe. These include a Fulbright Research Fellowship at 

Princeton University, USA, a research scientist at Dow Chemical and ICI Pty Ltd. Matt has also 

been a Visiting Professor at two of the largest Cancer Research Centres in the world: The Dana 

Farber Cancer Research Institute, Harvard Medical School, Boston (2000), and the Fred Hutchinson 

Cancer Research Centre, Seattle (2008). Matt is internationally recognised for his innovative and 

cross-disciplinary research at the interface between chemistry, nanotechnology, biology and 

medicine. He has co-authored more than 170 publications, many of which appear in the highest 

impact journals in his field, e.g., eight Science and Nature family journal publications overall to 

date – many of which have been highly cited. Over the past 10 years, he has raised greater than 

M$35 of competitive (category 1) research funding to support his work. His major awards and 

honours include an ARC Federation Fellowship (one of the most prestigious scientific fellowships 

in Australia), a Fulbright Research Fellowship to the US, a “Young Tall Poppy" Award for 

Queensland, a UQ Foundation/Vice Chancellor’s Research Excellence Award, a Paul Harris 

Fellowship, and a Pink Circle Award for breast cancer research excellence. Among other grants, 

Matt is currently the lead investigator on a 5-year M$5 national collaborative research grant from 

the National Breast Cancer Foundation (“Enabling Clinical Epigenetic Diagnostics: The Next 

Generation of Personalized Breast Cancer Care“). 

Matt has also initiated and led several large international multidisciplinary programs that involve 

close collaboration between leading nanotechnologists, molecular biologists, geneticists and 

commercial researchers. Significant examples include: 

1. A $4 million National and International Research Alliances Program (NIRAP) grant from 

the Queensland government, "International Partnership for Preventative and Personalised 

Medicine" (2009-11). An international collaborative grant between UQ, the Fred 

Hutchinson Cancer Research Centre (Seattle), the Seattle Biomedical Research Institute, and 

the University of Washington (Seattle). This consortium involved some of the highest 

calibre scientists in the world, e.g. Dr Lee Hartwell (2001 Nobel Laureate) from Seattle was 

a co-chief investigator on the grant. 

2. A $5 million National Institutes of Health (NIH) grant from the USA (co-lead with Prof 

Gerry Cangelosi, University of Washington, USA), “Accelerated Molecular Probe Pipeline” 

(2010-14). This consortium grant involves four partners across the US (University of 

Page 29



Washington, PATH and University of Virginia), with my lab being the only non-US 

member. The success rate for NIH grants in this round was 6%. 

3. A $5 million multidisciplinary National Collaborative grant from the National Breast Cancer 

Foundation (NBCF), "Novel strategies for Prediction and Control of Advanced Breast 

Cancer via Nanoscaled Epigenetic-Based Biosensors" (2008-2013). This consortium grant is 

a national collaboration involving leading geneticists, pathologists and oncologists from 

across Australia. Participating organisations include: the Garvan Institute (Sydney), the 

Peter MacCallum Centre (Melbourne), and the University of Newcastle and Queensland 

Health. At the time of award, this was the largest competitively won grant ever awarded by 

the NBCF (the largest philanthropic organisation that funds Australian research). In 2014, 

this grant was ranked as one of the top-ten performing grants ever awarded by the NBCF 

(out of hundreds of grants previously awarded). 

4. A second $5 million multidisciplinary collaborative grant from the NBCF, "Enabling 

Clinical Epigenetic Diagnostics: The Next Generation of Personalized Breast Cancer Care", 

2013-2018. This collaborative grant greatly expands on the achievements from the first 

NBCF collaborative grant. As well as the original CIs and collaborative institutions, new 

partners now also include: the Olivia Newton-John Cancer Research Centre (Melbourne), 

the Ludwig Cancer Research Centre (Melbourne), and Hunter Area Pathology Services 

(Newcastle). This second consortium grant is the only time that a second (follow-on) 

National Collaborative grant has ever been awarded by the NBCF (success rates of the 

individual NBCF National Collaborative rounds are typically around 8%, and rounds are 

held every two or three years). At a cumulative total of M$10, these two grants in aggregate 

represent almost 10% of the total NBCF investment in Australian research since the NBCF 

was founded ten years ago. 

Top 5 publications in the last 5 years that reflects scholarly works in nanotechnology and 

nano-diagnostics (of 90 publications 2012-16) 

1. Clark, S.; Stone, A.; Zotenko, E.; Locke, W.; Korbie, D.; Millar, E.; Pidsley, R.; Stirzaker, 

C.; Graham, P.; Trau, M.; Musgrove, E.; Nicholson, R.; Gee' J. DNA methylation of 

estrogen regulated enhancers defines endocrine sensitivity in breast cancer. Nature 

Communications, 6, 7758, 2015. 

2. Stirzaker, C., Zotenko, E., Song, J., Qu, W., Nair, S., Locke, W., Stone, A., Armstong, N., 

Robinson, M., Dobrovic, A., Avery-Kiejda, K., Peters, K., French, J., Stein, S., Korbie, D., 

Trau, M., Forbes, J., Scott, R., Brown, M., Francis, G., Clark, S., Methylome sequencing in 

triple negative breast cancer reveals distinct methylation clusters with prognostic value, 

Nature Communications, 6, 5899,2015. 

3. Connolly, A. R.; Trau, M., Rapid DNA detection by beacon-assisted detection 

amplification, Nature Protocols, 6, 772-778, 2011. 

4. Vaidyanathan, R., Naghibosadat, M., Rauf, S., Korbie, D., Carrascosa, L.G., Shiddiky, M., Trau, 

M., Detecting Exosomes Specifically: A Multiplexed Device based on Alternating Current 

Electrohydrodynamic Induced Nanoshearing, Analytical Chemistry, 86, 11125-11132, 2014. 

5. Lane, R. E., Korbie, D., Anderson, W., Vaidyanathan, R., Trau, M., Analysis of exosome 

purification methods using a model liposome system and tunable-resistive pulse sensing. 

Scientific Reports, 5, 13, 7639, 2015 (Nature award for “Top 100” paper for Sci. Rep. in 

2015). 

Page 30



CI F TRACK RECORD Prof Jon Hyett 

Career summary 

2008 – Current Head of the High Risk Obstetric Service, Royal Prince Alfred (RPA) Hospital, 

Sydney 

2011 – Current Clinical Professor and Joint Head of Discipline, Obstetrics and Gynaecology, 

Faculty of Medicine, University of Sydney 

Research Support 

2015 – 2020 AI on NHMRC Project Grant APP1078142, $951,296 Reducing cardiovascular risk 

in children born with poor fetal growth: the Small baby Omega-3 (SO3) trial 

2015 - 2018 Project PhD Supervisor on McKern/University of Sydney Grant $135,000 

2012 – 2016 CIC on NHMRC Project Grant APP1029644, $516,175 The POP-OUT Trial: 

Persistent Occipto- Posterior Position: Outcomes following rotation 

Contributions to field of Research 

Jon has >100 publications in peer-reviewed journals and is internationally recognised for his 

research linking the 12-week ultrasound finding of increased fetal nuchal translucency with 

structural heart defects. Jon was part of the team that developed an effective intrauterine therapy for 

twin twin transfusion syndrome and has been a leader in the clinical application of cffDNA for 

RHD and fetal chromosomal abnormality. 

2014 Conference Convenor, International Society for Prenatal Diagnosis Scientific co-chair. 

Presented peer selected oral abstract on impact of aspirin on prevalence of early onset 

preeclampsia. Invited speaker on prediction of gestational diabetes for pre congress course. 

2014 Invited Speaker, Asia Pacific Congress in Maternal and Fetal Medicine, Singapore 

Presented data on NIPT, invasive prenatal diagnosis and on 'near miss' analysis of adverse 

metal outcomes. Chaired session on fetal surgery. 

2014 Invited Speaker, International Society Ultrasound in Obstetrics and Gynaecology (ISUOG): 

Annual Scientific Meeting, Spain. Convenor and speaker at pre-congress course on NIPT. 

2014 Speaker selected from abstract, World Congress in Fetal Medicine, France Prediction and 

prevention of early onset pre-eclampsia. 

Research translation 

cffDNA for non-invasive genotyping of RHD and for contingent aneuploidy screening. 

Validation and demonstration of prediction and prevention of early onset pre-eclampsia. 


Charles Perkins Centre / University of Sydney 

Australasian Pre-eclampsia Research Network and the Australian Red Cross Blood Service 

Fetal Medicine Foundation (UK) 

Alberta Children’s Hospital Research Institute and the Danish Fetal Medicine Consortium 

Professional involvement 

2015 – Current Member Editorial Board, Associate Editor, Acta Obstet Gynecol Scand 

2010 – Current Member Editorial Board, Associate Editor, Prenatal Diagnosis 

2009 – Current Member Editorial Board, Associate Editor, Fetal Diagnosis and Therapy 

2014 Peer Reviewer, ANZJOG, BJOG, PLoS, Ultrasound Obstet and Gynecol 

2006 – Current NSW Medical Board 

2006 – Current Member RANZCOG 1st trimester screening committee 

1997 – Current Member RCOG, UK 

Supervision and mentoring 

Primary supervisor to five PhD students holders of University of Sydney scholarships. 

Five Masters’ students and one PhD student have completed in the last five years. 

Page 31



Peer Recognition and Service 

2013 – 2015 Assessor for Singaporean grant funding scheme 

2014 – 2015 Assessor for Hong Kong grant funding scheme 

2013 UK national research grant funding schemes. 

Contributions to NHMRC 

2014 NHMRC Research Translation Faculty 

2013 - 2015 NHMRC External Assessor for project grants 

Top 5 publications in the last 5 years 

1: Park F, Russo K, Williams P, Pelosi M, Puddephatt R, Walter M, Leung C, Saaid R, Rawashdeh 

H, Ogle R, Hyett J. Prediction and prevention of early onset pre-eclampsia: The impact of aspirin 

after first trimester screening. Ultrasound Obstet Gynecol 2015; 46: 419-423. 

This prospective cohort study documents the value of prediction (with a 12 week algorithm defining 

risk for ePET) and prevention (with low dose Aspirin as a therapeutic intervention) of early onset 

pre-eclampsia. 

2: Park FJ, Leung CH, Poon LC, Williams PF, Rothwell SJ, Hyett JA. Clinical evaluation of a first 

trimester algorithm predicting the risk of hypertensive disease of pregnancy. Aust N Z J Obstet 

Gynaecol 2013; 53: 532-9. 

A validation study demonstrated the effectiveness of a first trimester algorithm for predicting risk of 

early onset pre-eclampsia; demonstrating 90% sensitivity at 90% specificity. 

3: Ridding G, Schluter PJ, Hyett JA, McLennan AC. Uterine artery pulsatility index assessment at 

11-13 weeks' gestation. Fetal Diagn Ther 2014; 36: 299-304. 

This paper defines normal ranges for uterine artery PI at 12 weeks’ gestation in an Australian 

population; used in the prediction of risk of early onset pre-eclampsia. 

4: Leung C, Saaid R, Pedersen L, Park F, Poon L, Hyett J. Demographic factors that can be used to 

predict early-onset pre-eclampsia. J Matern Fetal Neonatal Med. 2014 [Epub ahead of print]. 

This paper describes demographic factors associated with the risk of developing early onset preeclampsia 

in an Australian population. It establishes the baseline for risk algorithms based on 

maternal demographic and investigational parameters. 

5: E Holanda Moura SB, Park F, Murthi P, Martins WP, Kane SC, Williams P, Hyett J, Silva Costa 

Fd. TNF-R1 as a first trimester marker for prediction of pre-eclampsia. J Matern Fetal Neonatal 

Med 2016; 29: 897-903. 

In collaboration with the group at The Royal Women’s Hospital in Melbourne, this paper explored 

the potential of other biomarkers for prediction of early onset pre-eclampsia. 

Research relevant to the proposed project 

Jon’s primary research interest is the prediction and prevention of adverse obstetric outcomes 

through population based screening. His research group has focused on developing predictive 

strategies for four major perinatal problems; screening for congenital abnormality, for preeclampsia 

and intrauterine growth restriction, for preterm birth and for gestational diabetes. All predictive 

testing occurs at 12 weeks’ gestation, the rationale being that this enables application of 

preventative interventions that will reduce the prevalence of disease. The group have had significant 

success in this area. Jon has lead the integration of some research findings into clinical practice. 

One example is the introduction of a pilot program demonstrating the effectiveness of prediction 

and prevention of pre-eclampsia; this program involves population-based assessment of maternal 

biophysical and biochemical parameters at the 12-week visit. High-risk women are treated with 

aspirin to prevent pre-eclampsia. This provides the platform on which women will be recruited to 

this study. 

Page 32



CI G TRACK RECORD: Dr. Carlos Salomon, PhD, MSc, BSc (Hons) 

Career summary 

2013-2016 University of Queensland Postdoctoral Fellowship, Brisbane Australia. 

2013- Staff, UQ Centre for Clinical Research (UQCCR), Brisbane, Australia. 

2013- Co-chair Early Career Researcher, International Federation of Placenta 

Association 

2009-2012 PhD program in Medical Science, School of Medicine, Pontificia 

Universidad Catolica de Chile 

Honours and Awards 

2013 Award excellence in doctoral thesis. Best PhD thesis, Pontificia Universidad Católica de 

Chile 

Best Basic Science Oral presentation. 22 nd annual Royal Brisbane and Women’s Hospital 

Healthcare Symposium 

2012 The University of Queensland Postdoctoral Research Fellowships 2013-2015 

University of Queensland Centre for Clinical Research (UQCCR), Brisbane, Australia. 

Sigma Aldrich Research Excellence Awards, Society for Gynecologic Investigation. 

International Federation of Placenta Associations (IFPA) Y.W. Charlie Locke Awards 

CONICYT (Comisión Nacional de Investigación Científica y Tecnológica) 

Internship Fellowship, UQCCR, Brisbane, Australia. 

UQCCR, Internship Fellowship 


Support fellowship for doctoral thesis, Chile. 

2011 International Federation of Placenta Associations (IFPA) Y.W. Charlie Locke Awards ( 

VRAID (Vicerrectoría Adjunta de Investigación y Doctorado) Internship Fellowship, 

University Texas Health Science Center for Pregnancy and Newborn Research, USA. 


PhD Fellowship, Chile. 

CONICYT, Support to the participation in national meetings, Chile. 

2010 CONICYT, Support for participation in national meetings, Chile. 

VRAID , Fellowship Academic Instructor, Pontificia Universidad Católica de Chile. 

USPI (Universidade de São Paulo, Brazil), Support for participation in 

postgraduate workshop, Brazil 

Awards, Best Seminar, Workshop "Maternal Fetal", Universidade de São Paulo, Brazil. 

SCHRD (Sociedad Chilena de Reproducción y Desarrollo) 

Support for participation in anual meeting, Chile. 

Research Support 

2013-2016 University of Queensland Postdoctoral Fellowship AU$300,000 

2010-2012 Comision Nacional de Ciencia y Tecnologia de Chile (CONICYT), AU$6,000 

2009-2010 Vice-rectoría de investigación, Ponticifia Universidad Católica de Chile, AU$2,000 

Contribution to the field of research (selected) 

2013 Invited Speaker “Exosomes: surrogate biomarkers of placental function” UQCCR Seminars 

Series, The University of Queensland, Brisbane. Australia. 

Invited Speaker “The role of placental exosomes in intercellular communication in health 

and disease”. NUS-UQ Research Day @ The Changing Panorama of Women’s Health: 

Navigating New Frontiers 9 th Singapore International Congress of O&G 2013. 

Invited Speaker “Placento-Maternal Transfection: Exosomes as surrogate biomarkers of 

placental function”. Society for Reproductive Biology meeting, Australian & New Zealand 

Placental Research Association, Sydney Australia, 2013. 

Page 33



Invited Speaker: Workshop “Stem cells: from biology to pathology”. International 

Federation of Placental Associations (IFPA) 2013, Whistler, CA. 

Invited Speaker: Workshop “Oxygen in placenta development and pathologies”. 

International Federation of Placental Associations (IFPA) 2013, Whistler, CA. 

Invited Speaker: Workshop “Use of ‘omics’ in understanding placental development and 

pathologies”. International Federation of Placental Associations (IFPA) 2013, Whistler, CA. 

Collaborations - International - University of the Andes and Catholic University of Chile, Santiago 

(4 reviews, 4 papers) 

Community engagement and participation 

Professional Involvement 

2012- Co-chair Early Carrier Researcher, International Federation of Placenta Associations. 

Supervision and Mentoring Honours 1 (1 current); MSc 0 (1 current); PhD 3 current 

Peer Recognition and Service 

2013 NHMRC Grant Reviewer 

Top 5 Publication in the last 5 years 

1. Salomon C, Kobayashi M, Ashman K, J, Sobrevia L, 2 Mitchell MD, Rice GE (2013) 

Hypoxia-induced changes in the bioactivity of cytotrophoblast-derived exosomes. PLoS 

ONE 8(11):e79636. doi: 10.1371/journal.pone.0079636. 

2. Salomon C, Ryan J, Sobrevia L, Kobayashi M, Ashman K, Mitchell M, Rice GE. Exosomal 

signalling during hypoxia mediates microvascular endothelial cell migration and 

vasculogenesis. (2013) PLoS One. Jul 8;8(7):e68451. doi: 10.1371/journal.pone.0068451. 

3. Kobayashi M, Salomon C, Tapia J, Illanes, SE, Mitchell MD, Rice GE (2014) Ovarian 

cancer cell invasiveness is associated with discordant exosomal sequestration of Let-7 

miRNA and miR-200. J. Translational Medicine 12:4. doi:10.1186/1479-5876-12-4 

The above 3 papers establish leadership in exosome biology and analysis applied to 

placental development and oncology. 

4. Westermeier F, Salomon C, González M, Puebla C, Guzmán-Gutiérrez E, Cifuentes F, 

Leiva A, Casanello P, Sobrevia L. (2011) Insulin restores gestational diabetes mellitusreduced 

adenosine transport involving differential expression of insulin receptor isoforms in 

human umbilical vein endothelium. Diabetes 60(6):1677-87. doi: 10.2337/db11-0155. 

5. Salomon C, Guzmán-Gutiérrez E, Westermeier F, Puebla C, Leiva A, Casanello P, Sobrevia 

L. (2012) Insulin Requires of Insulin Receptors A and B to Restore a Normal Phenotype in 

Human Placental Microvascular Endothelium from Patients with Gestational Diabetes 

Mellitus. PLoSONE; 7(7):e40578. doi: 10.1371/journal.pone.0040578. 

Paper 4 and 5 establish expertise in cell signalling and, in particular, in regulating placental 

vascular function. 

Page 34



CI H Professor David McIntyre 

Top 5 publications 

1) Mamun AA, Sutharsan R, O'Callaghan M, Williams G, Najman J, McIntyre HD, Callaway 

L. Cesarean Delivery and the Long-Term Risk of Offspring Obesity. Obstet Gynecol. 2013 

Nov 6. [Epub ahead of print] PubMed PMID: 24201680. This report addresses the putative 

influence of delivery by cesarean section and later obesity, refuting this association in a 

large Australian birth cohort with long term follow up. 

2) McIntyre HD, Gibbons KS, Flenady VJ, Callaway LK. Overweight and obesity in 

Australian mothers: epidemic or endemic? Med J Aust. 2012;196(3):184-8. This large 

epidemiologic study provides the most comprehensive long term data on the “obesity 

epidemic” and its relationship to a wide range of adverse pregnancy outcome in a birth 

cohort from the Mater Mothers’ Hospital in Brisbane. 

3) Catalano PM, McIntyre HD, Cruickshank JK, McCance DR, Dyer AR, Metzger BE, et al. 

The Hyperglycemia and Adverse Pregnancy Outcome Study: Associations of GDM and 

obesity with pregnancy outcomes. Diabetes Care. 2012;35(4):780-6. This study outlines the 

relative contributions of mildly elevated blood glucose levels and maternal obesity to 

adverse pregnancy outcomes. 

4) Flenady V, Koopmans L, Middleton P, Froen JF, Smith GC, Gibbons K, et al. Major risk 

factors for stillbirth in high-income countries: a systematic review and meta-analysis. 

Lancet. 2011;377(9774):1331-40. This systematic review outlines the major demographic 

and medical risk factors for still birth in the “developed world”, emphasising the 

importance of maternal obesity and diabetes. 

5) Barrett HL, Dekker Nitert M, McIntyre HD, Callaway LK. Normalizing metabolism in 

diabetic pregnancy: is it time to target lipids? Diabetes Care. 2014 May;37(5):1484-93. doi: 

0.2337/dc13-1934. PubMed PMID: 24757231. This major review in a highly cited journal 

considers the clinical relevance of treatments directed at modification of lipid parameters in 

pregnancies complicated by diabetes. 

OVERALL TRACK RECORD with an emphasis on the past 5 years 

Publications/Patents: I have published a total of 141 articles and 4 book chapters, with 57 articles 

in the last 5 years. The majority of these publications were achieved whilst working in a busy 

clinical role as I have had a part time research appointment (0.3 FTE) only since mid-2008, with no 

protected research time prior to this date. My recent publications are mostly in highly ranked 

specialist journals covering diabetes and obstetrics. My publications have received over 3400 

citations from other scientists and my “h” index via Google scholar is 29. 

Research Support: My research has attracted over $11.8M in funding as CI, including grants from 

NHMRC, National Institutes of Health (USA) and Canadian Institute for Health Research as well as 

smaller scale local grants (Diabetes Australia Research Trust, Queensland Health Strategic 

Partnerships, International Institute of Health (George Institute) and some pharmaceutical industry 

funding. 

Prizes (past 5y): 

INTERNATIONAL: Honorary membership of Diabetes in Pregnancy Study Group of the European 

Association for the Study of Diabetes, invited presentations to the Diabetes and Reproductive 

Health Interest Group of the American Diabetes Association (2011, 2013, 2015, 2016). Awarded 

Norbert Freinkel lecture (ADA) for 2016. 

NATIONAL: Invited presentations to the Developmental Origins of Health and Disease Society of 

Australia and New Zealand (2014) and Australasian Diabetes in Pregnancy Society (2014) 

International / National Reputation: I am a regular speaker at international and national meetings 

with over 40 presentations over the last 5 years, including invited presentations at peak gatherings 

such as the American Diabetes Association, International Federation of Gynecology and Obstetrics, 

Controversies in Gynecology, Obstetrics and Maternal Fetal Medicine and Diabetes in Pregnancy 

Page 35



meetings. I am frequently asked to serve as session chair at such meetings. I frequently undertake 

duties as a reviewer for high impact journals including Diabetes Care, Diabetologia, Clinical 

Endocrinology and the Journal of Clinical Endocrinology and Metabolism. I have recently been 

appointed as an Editorial Board Member for the premier clinical diabetes journal “Diabetes Care”. 

I currently serve as Chair of the International Association of Diabetes in Pregnancy Study Groups 

and I am an invited member of the FIGO Hyperglycemia in Pregnancy Workgroup 

Research Translation: 

Direct impact on clinical practice: 

• Testing for GDM. I have been centrally involved in the development and dissemination of 

the IADPSG recommendations for diagnosis of GDM. This has included membership of 

consensus conference which developed the consensus process and of the writing group 

which finalized the proposed criteria. On a national level, I have been involved in 

representations to the college of Obstetrics and Gynecology, ADIPS and the Australian 

Diabetes Society (ADS) as well as local within the Mater Mothers Hospital and on a 

Queensland level, where I have been Chair of the GDM workgroup for the Statewide 

Clinical Diabetes Network. Internationally, I have been closely involved in this process as 

Chair of IADPSG and a member of the FIGO GDM workgroup. 

• Intensive diabetes management. Since 2004, I have been a founding member of the 

OzDAFNE collaboration, which introduced the Dose Adjustment for Normal Eating 

(DAFNE) system of education in intensive insulin therapy for Type 1 diabetes patients into 

clinical practice in Australia. This has become the mainstay of such treatment in 

Queensland and is DAFNE courses are now offered in over 20 centres across Australia and 

New Zealand. 

• Type 2 diabetes management. As an investigator in the FIELD and ADVANCE studies, I 

have been an active participant in the integration of lipid lowering strategies and intensive 

blood pressure control strategies in the management of Type 2 diabetes. 

Clinical Practice Guidelines: 

I have participated in the development of clinical practice guidelines for Obesity in pregnancy via 

the Statewide Maternity and Neonatal Network and I served as Co-lead of the group which 

developed a guideline for GDM diagnosis and treatment published in 2015. 

Investigator-initiated Clinical Trials: 

• I have been involved in the MiG trial of metformin in the management of gestational 

diabetes and I have started the first Australian site for the “MiTY” (Metformin in Type 2 

diabetes) trial to further examine the use of this medication in pregnancy. 

• I am CI-B and lead at Mater Health Services for the “SPRING” (Supplementation with 

Probiotics in Gestation) trial which is examining the potential role for probiotics in GDM 

prevention. 

• I have initiated two RCTs dealing with lifestyle strategies in the prevention of progression to 

Type 2 diabetes following GDM. 

• I have been a CI on a further RCT “TRIM” (Trial of Weight Reduction in New Mums” 

dealing with optimal dietary follow up to reduce post-partum weight retention in obese 

pregnant women. 

Public Health: Through my role in the National Diabetes in Pregnancy Advisory Committee, I 

have contributed to definition of priorities for the care of women with diabetes before, during and 

after pregnancy. My contributions to GDM care also relate to Public Health as GDM is the 

commonest identifiable antecedent to overt Type 2 diabetes in parous women. 

Training: I have held advisory roles for 15 University of Queensland PhD candidates, of whom 8 

have successfully completed their degrees (7 ongoing). I am an associate advisor for one student 

based at the Menzies Institute in Darwin. In addition I developed and achieved accreditation for 

advanced physician training in Endocrinology and Obstetric Medicine at the Mater site and have 

supervised over 30 FRACP advanced trainees in these clinical areas. 

Page 36



CI I: Professor David Simmons 

Professor David Simmons is Professor of Medicine at Western Sydney University, Head of the 

Department of Endocrinology and Chair of the Clinical Council at Campbelltown Hospital, 

Professorial Fellow at the University of Melbourne and Diabetes Physician at Cambridge University 

Hospitals. His interest is in the prevention of diabetes and its complications on a population basis 

and he brings expertise in the areas of health service redesign, the conduct of clinical trials and 

clinical epidemiology to the proposal. He has just completed 7 years (2007-2014) as diabetes 

clinical lead at Cambridge University Hospitals, England, having been the Foundation chair in 

Rural Health at the University of Melbourne 1998-2002, and the Foundation chair in Medicine at 

the Waikato Clinical School, University of Auckland, New Zealand 2003-2007. He was President 

of the Australasian Diabetes in Pregnancy Society (ADIPS) 1998-2002 and one of the two first cochairs 

of the Australian National Diabetes in Pregnancy Advisory Committee 2001-2002. He was 

chair of the Diabetes UK Diabetes Health Care Professional Education steering group 2009-2014, 

which generated a national position statement on competency in diabetes care. He has been awarded 

over $20 million in research funding previously including over $5 million (including 2 NHMRC 

grants) since starting back in Australia in January 2015. He has published (or in press) 254 

scientific articles (5,739 citations (GS)) and 8 book chapters. 

Research relevant to the proposed project 

Professor Simmons has been researching the interplay between diabetes, insulin resistance and 

adiposity for over 25 years in both epidemiological and prevention/treatment studies, commencing 

with South Asians in Coventry (Coventry Diabetes Study), Polynesians in South Auckland (South 

Auckland Diabetes Project), rural Victorians (Crossroads studies), Waikato (New Zealand: Te Wai 

o Rona: Diabetes Prevention Strategy), Cambridgeshire (England: DALI (RCT for preventing 

gestational weight gain/gestational diabetes), RAPSID (RCT of per support to assist selfmanagement 

in type 2 diabetes), East Cambs and Fenland Diabetes Integrated Care Initiative). 

Mental health issues have featured as barriers to care and self-care across many of these studies and 

he led the Cambridge diabetes service initiative to prevent ‘recurrent diabetic ketoacidosis’-a 

condition where 60% of patients have mental health issues: admissions were reduced by 60%. 


1. Meek CL, Murphy HR, Simmons D. Random plasma glucose in early pregnancy is a better 

predictor of gestational diabetes diagnosis than maternal obesity. Diabetologia, 2015. 

2. Simmons D, Jelsma JG, Galjaard S, Devlieger R, van Assche A, Jans G, et al. Results From a 

European Multicenter Randomized Trial of Physical Activity and/or Healthy Eating to Reduce 

the Risk of Gestational Diabetes Mellitus: The DALI Lifestyle Pilot. Diabetes Care, 

2015;38:1650-1656. 

3. Simmons D, Hartnell S, Watts J, Ward C, Davenport K, Gunn E, Jenaway A. Effectiveness of 

a multidisciplinary team approach to the prevention of readmission from acute glycaemic 

events. Diab Med. 2015: 1-7. 

4. Simmons D, Prevost AT, Bunn C, Holman D, Parker RA, Cohn S, Donald S, Paddison CAM, 

Ward C, Robins P, Graffy J. Impact of community based peer support in Type 2 diabetes: A 

cluster randomised controlled trial of individual and/or group approaches. PLOS One, 2015; 1- 

13. 

5. Yu D, Simmons D. Association between blood pressure and risk of cardiovascular hospital 

admissions among people with type 2 diabetes. Heart 2014;100:1444-1449. 

For papers 2-5, Professor Simmons role was as principal investigator (PI), leading in study design, 

and responsibility for the ethics submission, recruitment, implementation and publication. For 

paper 1, Professor Simmons was the senior author and supervised the analysis and publication. 

Page 37



Overall track record in the last 5 years 

In spite of his heavy clinical and management responsibilities, over the last 5 years, Professor 

Simmons has generated 62 refereed publications, over 60 conference presentations and $11 million 

of research funding (mainly as PI or co-PI). He is currently the editor of a book on diabetes 

integrated care for Springer publications. His evaluated service designs won 3 of the 13 national 

QiC diabetes awards in 2013, his recurrent diabetic keto-acidosis prevention programme is reported 

as national best practice by the Joint British Diabetes Societies (December 2013). His research into 

diabetes in pregnancy has led to the Joseph Hoet award from the Diabetes in Pregnancy Study 

Group in 2009 with sentinel studies in the use of insulin pumps in GDM/Type 2 diabetes, random 

glucose screening at booking in pregnancy, the impact of the intrauterine milieu on Polynesian 

babies including their relative hyperleptinaemia at birth and the Australia/New Zealand pilot of 

diabetes in pregnancy structured audit and benchmarking. He was the only English/New Zealand 

member of the 2009 International Association Diabetes in Pregnancy Study Group consensus panel 

and one of 16 external experts for the 2013 World Health Organisation Diagnostic Criteria and 

Classification of Hyperglycaemia First Detected in Pregnancy. 

He has a proven track record in the conduct and coordination of clinical trials, epidemiological 

research and evaluated service development. Over the last 5 years, he has (i) successfully completed 

a National Institute for Health Research (NIHR) funded evaluation (as PI) of an integrated diabetes 

service in Cambridgeshire (n=8,000), leading to changes in the way that diabetes is delivered in the 

county (ii) successfully completed the largest global Randomised Controlled Trial of diabetes peer 

support (Peers for Progress/NIHR funded- RAPSID n=1,299-as PI) which has just had a £0.5 

million project funded to translate findings across 8 sites in the UK (iii) he has just finished as the 

trial coordinator, UK PI and overall deputy PI for DALI (Vitamin D and Lifestyle Intervention for 

the prevention of gestational diabetes), the EU FP7 funded RCT for the prevention of GDM across 

9 European countries. (iv) is a co-investigator for CONCEPTT, an international multicentre RCT 

of continuous glucose monitoring in pregnant and ‘pre-pregnant’ women with type 1 diabetes (v) 

He is one of the 17 PIs in The Australian and New Zealand Diabetes and Cancer Collaboration 

(ANZDCC), using data from the Crossroads Undiagnosed Disease Study 1999-2003. 

Professor Simmons is the clinical lead for the Cambridge Diabetes Education Programme, a Health 

Innovation and Education Cluster funded initiative, the first on line resource to comprehensively 

implement health care professional competency frameworks. In 2013, he was awarded the Diabetes 

UK Janet Kinson award for his achievements in educational research/development. He referees for 

multiple journals and has been an examiner for 4 PhD students (Denmark*2, Ireland, Australia) and 

international grants from Australia, Canada, New Zealand, Ireland and Wales. He still cosupervises 

one Doctor of Health Psychology (London) student in the UK. He has been a primary or 

co-supervisor for 4 PhD completions, 4 Masters students, 1 honours student in the past. He is an 

advisor to the Swedish National Diabetes in Pregnancy Register research in Orebro and Chief 

Technical Advisor to the Tongan GDM Taskforce. 

Page 38



CIJ: Professor Sailesh Kumar (MBBS MMed(O&G) FRCS FRCOG FRANZCOG DPhil(Oxon) 

CMFM) 


1. The relationship between maternal placental growth factor levels and intrapartum fetal 

compromise. L Bligh, R Greer, S Kumar. Placenta, Vol. 48, p63–67. Published online: October 

14, 2016 This paper details the association between low maternal PlGF levels and intrapartum 

complications and poor neonatal outcomes. It is the first report of this association in term 

pregnancies and provides evidence for the potential incorporation of this biomarker into a 

screening test for late pregnancy complications. 

2. Are babies that fail to reach their genetic growth potential at increased risk of intra-partum fetal 

compromise? Prior T, Paramasivam G, Bennett P, Kumar S. Ultrasound Obstet Gynecol. 2014 Dec 

9. doi: 10.1002/uog.14758. This paper demonstrated that term fetuses that developed intrapartum 

compromise had circulatory changes suggestive of suboptimal growth despite normal birthweights. 

The evidence presented in this paper is part of a small but growing body of evidence that challenges 

the conventionally held view that intrapartum fetal compromise is unpredictable. 

3. The magnitude of change in the fetal cerebro-placental ratio in the third trimester and the risk of 

adverse pregnancy outcome. C Flatley, R Greer, S Kumar. Ultrasound Obstet Gynecol. 2016 Nov 

22. doi: 10.1002/uog.17371.This paper demonstrated that the magnitude of change in the CPR 

influences the risk of intrapartum complications and adverse outcome providing evidence for the 

value of a late third trimester scan. 

4. Prediction of fetal compromise in labor. Prior T, Mullins E, Bennett P, Kumar S. Obstet 

Gynecol. 2014 Jun; 123(6):1263-71. This paper detailed a screening test for intrapartum 

compromise utilising the fetal cerebro-umbilical ratio and umbilical venous flow and demonstrated 

that it was capable of identifying the majority of fetuses at risk. It also showed that the test had a 

negative predictive value for intrapartum compromise of almost 100%. 

5. Prediction of intrapartum fetal compromise using the cerebroumbilical ratio: a prospective 

observational study. Prior T, Mullins E, Bennett P, Kumar S. Am J Obstet Gynecol. 2012 Nov 15. 

This was the first prospective study evaluating the utility of the fetal cerebro-umbilical ratio to 

predict intrapartum compromise. The results of this study demonstrated that identification of fetuses 

at risk was possible in an apparently low risk cohort. 

Overall Track Record in the last 5 years 

Career summary: Prof Kumar is a Maternal & Fetal Medicine Subspecialist at the Mater Mothers’ 

Hospital in Brisbane and Head of the Academic Discipline of Obstetrics & Gynaecology at the 

University of Queensland. He leads an active research group collaborating across specialties both in 

basic science as well as clinical projects. He is also Visiting Professor at Imperial College London. 

He is actively involved in both clinical practice and research. 

Research Support: Prof Kumar has been a named investigator on grants worth >$2M both in the 

UK and in Australia including from the NHMRC. 

Contribution to the field of research: Prof Kumar’s current research programme has made 

significant contributions towards identifying at risk fetuses in late pregnancy. He has been invited to 

present his research findings at many national and international meetings and has given several key 

note lectures. His research contribution is evident in the research output of his group and the prizes 

won by some of his students. His area of research is particularly relevant in obstetrics given the 

appalling perinatal outcomes in low and middle income countries with high rates of stillbirth and 

other adverse pregnancy outcomes. He has authored/co-authored more than 80 peer reviewed 

papers, 18 book chapters and has written a textbook of fetal medicine. Over the last five years, Prof 

Kumar has authored over 40 publications. The majority of his publications is in the area of adverse 

pregnancy outcome, fetal growth restriction and fetal therapy. In recognition of Prof Kumar’s 

Page 39



professional achievements and contributions to the NHS in the UK, he was awarded a Bronze/Level 

9 Clinical Excellence Award in 2008 at the age of 42 years (The average age to attain this award 

nationally is 49 years). In 2010/2011, the Times newspaper undertook an exercise to identify 

Britain's leading specialists based on information from professional bodies. Prof Kumar was one of 

only 2 fetal medicine specialists on this list. 

Professional Involvement: In the UK he was a specialist advisor to the National Institute of 

Clinical Excellence for Fetal Medicine interventional procedures and reviewed some fetal medicine 

guidelines prior to publication. He was also a clinical advisor to the Healthcare Commission and 

gave advice on complex cases where local resolution had failed. He organised (since 2008) an 

annual Clinical Fetal Medicine Course at Imperial College, London which was aimed at advanced 

and subspecialty trainees in maternal and fetal medicine and specialists involved in perinatal care. 

This was an extremely popular course and attracted numerous local and international delegates. Prof 

Kumar has co-authored a RCOG guideline pertaining to the management of women with red cell 

antibodies in pregnancy. These guidelines influence and guide practice in many different countries. 

In addition, he was also a member of the Fetal & Neonatal Transfusion sub-committee of the British 

Committee for Standards in Haematology (BCSH) and contributed to the most recent set of 

guidelines. At the Mater Mothers’ Hospital/Mater Research Institute he is a member of the Human 

Research Ethics Committee. 

International standing: Prof Kumar is regularly invited to speak at international conferences 

including International Society for Prenatal Diagnosis, RANZCOG/RCOG, International Society of 

Obstetrics and Gynaecology Ultrasound, Singapore College of Obstetrics & Gynaecology and Hong 

Kong University. 

Supervision and/or mentoring: Prof Kumar is currently supervising 7 PhD and 3 Honours 

students and 8 medical student projects and is leading an RCT investigating the utility of Sildenafil 

to reduce the risk of intrapartum fetal compromise. In the UK, he has supervised to completion 5 

PhD students and 22 Masters students. In the UK, Prof Kumar was Clinical Programme Supervisor 

for the Maternal & Fetal Medicine Subspecialty training programme at Imperial College as well as 

preceptor for the Advanced Training Special Skills Module (ATSM) in Fetal Medicine for the 

Northwest Thames Perinatal Network 

Peer review involvement: Prof Kumar has reviewed for a number of international journals 

including Placenta, Prenatal Diagnosis, Journal of Maternal-Fetal Medicine and Neonatology, 

Journal of Perinatology, Australian & New Zealand Journal of Obstetrics & Gynaecology, 

Ultrasound in Obstetrics and Gynaecology and PLOSOne. In 2012 he was invited to be an 

associate editor of the journal Fetal and Maternal Medicine Review, Cambridge University Press. 

Contribution to the NHMRC and other funding agencies: Prof Kumar has reviewed funding 

proposals from the NHMRC and Wellcome Trust and other funding bodies. 

Page 40



Associate Investigator (AI) Contribution, 

The AI team provides a pathway to end user organisations and will play a significant role within 

this CRE that will enable to CRE to influence policy and practice locally, nationally and 

internationally. 

AI – Professor Leonie Callaway holds a conjoint position as Head, Royal Brisbane Clinical 

School, and Senior Specialist in Obstetric and Internal Medicine at the Royal Brisbane and 

Women's Hospital. Prof Callaway is Deputy Chair of the Queensland Maternal and Perinatal 

Quality Council, and Co-Chair of the Queensland Clinician Scientists Association. Prof Callaway 

has an outstanding research track record in obesity and inflammation in pregnancy, the role of the 

maternal metabolism on fetal programming and neonatal body composition, lifestyle interventions 

in pregnancy, the role of pregnancy in unmasking the risks of future chronic disease and probiotics 

for the prevention of gestational diabetes mellitus. Prof Callaway is a member of the Council for the 

Australian Diabetes in Pregnancy Society, and is Deputy Chair of the Queensland Maternal and 

Perinatal Quality Council. Prof Callaway has an active interest in guideline development to support 

translation of research into clinical practice. Together with Dekker Nitert is a lead clinical 

researcher in the SPRING RTC study of probiotics in the prevention of gestational diabetes mellitus 

in overweight and obese women. Prof Callaway have a critical role in the translation of CRE 

research outcome into practice and policy change. 

AI- Professor Alan Rowan is Director of the Australian Institute for Bioengineering and 

Nanotechnology. He was awarded an ARC laureate in 2016 in the area of biomimetic materials and 

has active research in the fields of regenerative medicine, wound care, immunotherapy and 

nanomedicine. He co-director of the UQ StemCare center for stem cell ageing and a board member 

of the Dow Centre for Sustainable Engineering Innovation. Prof Rowan is co-founder of four spin 

companies Noviocell, Noviotech, Encapson and Wound-X in the field of biomaterials and their 

medical applications. Prof Rowan will play a crucial role in the transactional of new technological 

advances in bio engineering and nanotechnology into clinical practice. In particular, Prof Rowan 

will contribute to the development of exosome-based diagnostics and the development of new 

point- of-care medical devices. Prof Rowan will also leverage his extensive industry partnerships to 

provide in-house opportunities for career development and training for postdoctoral fellows and 

students involved in the CRE. 

AI-A/Prof Greg Duncombe is an active clinician scientist, with clinical involvement in many local 

institutions and access to Australia-wide clinical and basic science collaborations. He is the main 

clinical lead/connection between the exosome lab scientists at UQCCR and the local obstetric 

population in regards to fetal and maternal medicine research candidates (including GDM and 

others) and specimen availability. AI-Duncombe is the current Chair of the Maternal Fetal 

Medicine Subspecialty (MFM) in Australia and has unparalleled access to subspecialty trainees and 

colleagues and key responsibilities for development of guidelines. A/Prof Duncombe has played a 

crucial role in establishing clinical partnerships across the CRE collaborative network. In addition, 

he has an active collaborator in the exosomes signalling and biomarker aspects of the CRE. 

AI-A/Prof Anusch Yazdani is Director of Clinical Research and Development at Queensland 

Fertility Group Research Foundation. He is a distinguished subspecialist in reproductive 

endocrinology, infertility and minimally invasive pelvic surgery. He is the Program Director for 

Endoscopic Surgery and Reproductive Endocrinology at Eve Health and Director of Research at the 

Queensland Fertility Group. A/Prof Yazdani is a collaborator on ART research projects. Within the 

Queensland Fertility Group (QFG) he has facilitated access to human embryo-conditioned culture 

media for analysis. QFG staff collect and process these valuable clinical samples for the CRE team 

Page 41



and coordinate access to clinical records. 

contribution to the work of the CRE. 

As such they make extremely valuable in kind 

AI- A/Prof David Whiley is employed concurrently by The University of Queensland working at 

UQCCR and Pathology Queensland an organisation occupying the adjacent building. A/Prof 

Whiley has expertise in the successful development and implementation of in vitro diagnostics and 

their implementation to clinical practice. His working environment at Pathology Queensland 

contributes a clear pathway for translation. A/Prof Whiley conducts the development all phases of 

IVD development within the Centre of a Clinical Research and work closely with CRE members 

within the facility. He will play crucial role in is the translation of new screening tests into routine 

clinical pathology services. 

AI-Prof Karen Moritz is Director of the children’s health research Centre, University of 

Queensland and an NH&MRC Senior Research Fellow in the School of Biomedical Sciences at the 

University of Queensland. The aim of her work is to understand how prenatal perturbations 

contribute to an increased risk of developing cardiovascular, renal and metabolic disease in 

adulthood. Over the last 5-7 years, her research has focused on determining the pivotal role played 

by the kidney in the “developmental programming” of adult disease. Her research has shown a 

reduced nephron endowment is associated with hypertension and renal impairment in the adult 

following excess maternal glucocorticoid exposure, maternal low protein diet, placental 

insufficiency and most recently, prenatal alcohol exposure. Prof Moritz will play a substantive role 

in assessing the impact of complications of pregnancy on pregnancy and neonatal outcome and the 

development and evaluation of intervention strategies. 

AI – Dr Sarah Reed is the Head of the Mass Spectrometry Facility at the University of Queensland 

Centre for Clinical Research. She has over 12 years of experience in mass spectrometry across the 

research areas of proteomics, lipidomics, metabolomics, tissue imaging and small molecule 

analysis. Her background is from the industry where she was appointed as the senior application 

specialist for a global mass spectrometry company and was integral in the development, 

implementation and education of new technologies and workflows to researchers across Australia, 

New Zealand and the Rest of Asia regions. AI Reed is also involved in implementing and 

maintaining the international industry standard environment (ISO17025, ISO13485) within the 

facility. Dr Reid’s role in the CRC is one of a technical regulatory compliant expert. 

AI-Prof Annemarie Hennessy is the Dean of Medicine at the School of Medicine and currently 

holds the position of Foundation Professor of Medicine. Profe Hennessy is an active obstetric and 

renal physician based at the Campbelltown Hospital. Prof Hennessy has an extensive research track 

record in preeclampsia research and is actively involved in clinical and laboratory research into the 

causes of high blood pressure during pregnancy; collaborating with hospitals in Sydney, Canada 

and the USA. Her contribution to this CRE is indispensable for the successful completion of T3 

and T4 activities and for mentoring and training of clinical researcher and practitioners. 

AI – Dr Marloes Dekker Dr Dekker’s research focuses on the role of metabolism in 

complications of pregnancy. Dr Dekker is a Senior Lecturer in the School of Biomedical Sciences 

and heads a research group at the UQ Centre for Clinical Research studying the role of the gut 

microbiome in pregnancy, the role of food additives on placental function and placental gene 

expression and epigenetic markers in pregnancy complications. Dr Dekker works closely with 

clinician-scientists and clinicians at the Royal Brisbane and Women’s Hospital. She is part of the 

SPRING RCT team which assesses if probiotics can prevent gestational diabetes mellitus in 

overweight and obese women. Dr Dekker is a scientific representative on the SOMANZ council. 

Page 42



Consumer and Community Participation 

This work of this CRE is Precision Medicine that involves translation of research excellence and 

cutting edge technology through quality management systems into personalised medicine. The 

need for validation of personalised Medicine by end user populations is self-evident. While 

successful outcomes will be honed from presenting populations of mothers and babies, it is critical 

to the legacy of this CRE that those for whom successful pregnancy outcomes have not been 

possible will continue to have involvement. The CRE will endeavour to secure on going 

involvement of its end user populations and advocacy groups through the established health care 

provider organisations within its collaborative network but also directly through education 

programs offered to address lifestyle factors at preconception. Those who have experienced 

miscarriage and still birth are more likely to be engaged through the medium of support groups. 

The current engagement activities of the CRE CI and AI will be leveraged into CRE portfolio. The 

activities include their existing connections with stakeholder groups through which it is proposed 

the CRE will convene forums through which feedback and opinion may be elicited for new service 

models for improving pre-conception care and early pregnancy risk engagement. It is anticipated 

that the following engagements will be enhanced and strengthened by participation of other CIs; 

new engagements will be built: 

Professor Simmons is the clinical lead for the Cambridge Diabetes Education Programme, a Health 

Innovation and Education Cluster funded initiative, the first on line resource to comprehensively 

imple Professor Simmons presents to the local community (e.g. Rotary) on Diabetes. AHSP DOMS 

has set up an Aboriginal Reference group, a CALD reference group and a stakeholder group 

(including Diabetes Australia-NSW, Juvenile Diabetes Research Foundation, Pharma companies, 

Health Services). Prof Simmons engages with community group as President, Australasian 

Diabetes in Pregnancy Society (ADIPS 1998-2002); Co-Chair, National Diabetes in Pregnancy 

Advisory Committee, Australia (2001-2002); Co-Chair, NZ National GDM Working Group (2006); 

Diabetes UK Health Professional Education Chair (2010-2014); Mid Essex Clinical Commissioning 

Group (2013-2014); Deputy Divisional Director, Division of Medicine, CUH (2011-2014). He has 

also set up a Clinician Reference Group in Wollondilly for the Wollondilly Diabetes Programme 

(an integrated diabetes service). 

Professor Hyett contributes to ‘Miracle Babies’ as community advocates for a threatened preterm 

labor project being established across NSW and is involved in the James Lind style Charles Perkins 

Centre forum to identify research questions for the proposed Baby1000 (examining impacts of 

interventions through fetal life to two years of age) project. He has been involved in establishing the 

RPA/Sydney Local Health District iSAIL stillbirth clinic through community support (Canterbury 

NSW Leagues Club). 

Professor Colditz has a long standing involvement in supporting health consumer and advocacy 

organisations. He is currently a board member of the national SIDS & Kids Foundation. He has 

been awarded the Ray Phippard Award for services to medical research by the Lions Medical 

Research Foundation. In 2013 he was awarded life membership of SIDS & Kids (QLD). 

Page 43



References 

1. Barker DJ. The developmental origins of adult disease. Eur J Epidemiol 2003; 18(8): 733-6. 

2. Barker DJ. The developmental origins of chronic adult disease. Acta Paediatr Suppl 2004; 

93(446): 26-33. 

3. Ryckman KK, Borowski KS, Parikh NI, Saftlas AF. Pregnancy Complications and the Risk 

of Metabolic Syndrome for the Offspring. Curr Cardiovasc Risk Rep 2013; 7(3): 217-23. 

4. Park FJ, Leung CH, Poon LC, Williams PF, Rothwell SJ, Hyett JA. Clinical evaluation of a 

first trimester algorithm predicting the risk of hypertensive disease of pregnancy. Aust N Z J 

Obstet Gynaecol 2013; 53(6): 532-9. 

5. Manten GT, Sikkema MJ, Voorbij HA, Visser GH, Bruinse HW, Franx A. Risk factors for 

cardiovascular disease in women with a history of pregnancy complicated by preeclampsia 

or intrauterine growth restriction. Hypertens Pregnancy 2007; 26(1): 39-50. 

6. Christensen M, Kronborg CS, Eldrup N, Rossen NB, Knudsen UB. Preeclampsia and 

cardiovascular disease risk assessment - Do arterial stiffness and atherosclerosis uncover 

increased risk ten years after delivery? Pregnancy Hypertens 2016; 6(2): 110-4. 

7. Williams D. Pregnancy: a stress test for life. Curr Opin Obstet Gynecol 2003; 15(6): 465-71. 

8. Cain MA, Salemi JL, Tanner JP, Kirby RS, Salihu HM, Louis JM. Pregnancy as a window 

to future health: maternal placental syndromes and short-term cardiovascular outcomes. Am 

J Obstet Gynecol 2016; 215(4): 484 e1- e14. 

9. Chasan-Taber L. It Is Time to View Pregnancy as a Stress Test. J Womens Health (Larchmt) 

2016; 25(1): 2-3. 

10. Sattar N, Greer IA. Pregnancy complications and maternal cardiovascular risk: opportunities 

for intervention and screening? BMJ 2002; 325(7356): 157-60. 

11. Mosca L, Benjamin EJ, Berra K, et al. Effectiveness-based guidelines for the prevention of 

cardiovascular disease in women--2011 update: a guideline from the American Heart 

Association. J Am Coll Cardiol 2011; 57(12): 1404-23. 

12. Bellamy L, Casas JP, Hingorani AD, Williams D. Type 2 diabetes mellitus after gestational 

diabetes: a systematic review and meta-analysis. Lancet 2009; 373(9677): 1773-9. 

13. Noussitou P, Monbaron D, Vial Y, Gaillard RC, Ruiz J. Gestational diabetes mellitus and 

the risk of metabolic syndrome: a population-based study in Lausanne, Switzerland. 

Diabetes Metab 2005; 31(4 Pt 1): 361-9. 

14. Kim C, Cheng YJ, Beckles GL. Cardiovascular disease risk profiles in women with histories 

of gestational diabetes but without current diabetes. Obstet Gynecol 2008; 112(4): 875-83. 

15. Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-eclampsia and risk of cardiovascular 

disease and cancer in later life: systematic review and meta-analysis. BMJ 2007; 335(7627): 

974. 

Page 44



16. Williams D. Long-term complications of preeclampsia. Semin Nephrol 2011; 31(1): 111-22. 

17. Robbins CL, Hutchings Y, Dietz PM, Kuklina EV, Callaghan WM. History of preterm birth 

and subsequent cardiovascular disease: a systematic review. Am J Obstet Gynecol 2014; 

210(4): 285-97. 

18. Simpson RJ, Jensen SS, Lim JW. Proteomic profiling of exosomes: current perspectives. 

Proteomics 2008; 8(19): 4083-99. 

19. Harding CV, Heuser JE, Stahl PD. Exosomes: looking back three decades and into the 

future. J Cell Biol 2013; 200(4): 367-71. 

20. Lener T, Gimona M, Aigner L, et al. Applying extracellular vesicles based therapeutics in 

clinical trials - an ISEV position paper. J Extracell Vesicles 2015; 4: 30087. 

21. Salomon C, Torres MJ, Kobayashi M, et al. A gestational profile of placental exosomes in 

maternal plasma and their effects on endothelial cell migration. PLoS One 2014; 9(6): 

e98667. 

22. Vaswani K, Ashman K, Reed S, et al. Applying SWATH Mass Spectrometry to Investigate 

Human Cervicovaginal Fluid During the Menstrual Cycle. Biol Reprod 2015; 93(2): 39. 

23. Escudero CA, Herlitz K, Troncoso F, et al. Role of Extracellular Vesicles and microRNAs 

on Dysfunctional Angiogenesis during Preeclamptic Pregnancies. Front Physiol 2016; 7: 98. 

24. Salomon C, Scholz-Romero K, Sarker S, et al. Gestational Diabetes Mellitus Is Associated 

With Changes in the Concentration and Bioactivity of Placenta-Derived Exosomes in 

Maternal Circulation Across Gestation. Diabetes 2016; 65(3): 598-609. 

25. Salomon C, Yee S, Scholz-Romero K, et al. Extravillous trophoblast cells-derived exosomes 

promote vascular smooth muscle cell migration. Front Pharmacol 2014; 5: 175. 

26. Wee EJ, Ngo TH, Trau M. Colorimetric detection of both total genomic and loci-specific 

DNA methylation from limited DNA inputs. Clin Epigenetics 2015; 7: 65. 

27. Rahnama F, Shafiei F, Gluckman PD, Mitchell MD, Lobie PE. Epigenetic regulation of 

human trophoblastic cell migration and invasion. Endocrinology 2006; 147(11): 5275-83. 

28. Rahnama F, Thompson B, Steiner M, Shafiei F, Lobie PE, Mitchell MD. Epigenetic 

regulation of E-cadherin controls endometrial receptivity. Endocrinology 2009; 150(3): 

1466-72. 

29. Jansen ME, Metternick-Jones SC, Lister KJ. International differences in the evaluation of 

conditions for newborn bloodspot screening: a review of scientific literature and policy 

documents. Eur J Hum Genet 2016. 

30. Wee EJ, Wang Y, Tsao SC, Trau M. Simple, Sensitive and Accurate Multiplex Detection of 

Clinically Important Melanoma DNA Mutations in Circulating Tumour DNA with SERS 

Nanotags. Theranostics 2016; 6(10): 1506-13. 

31. Edgell T, Martin-Roussety G, Barker G, et al. Phase II biomarker trial of a multimarker 

diagnostic for ovarian cancer. J Cancer Res Clin Oncol 2010; 136(7): 1079-88. 

32. Rice GE, Edgell TA, Autelitano DJ. Evaluation of midkine and anterior gradient 2 in a 

multimarker panel for the detection of ovarian cancer. J Exp Clin Cancer Res 2010; 29: 62. 

Page 45



33. Brunelli VB, Prefumo F. Quality of first trimester risk prediction models for pre-eclampsia: 

a systematic review. BJOG 2015; 122(7): 904-14. 

34. Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating 

characteristic (ROC) curve. Radiology 1982; 143(1): 29-36. 

35. Efron B. Bayesian inference and the parametric bootstrap. Ann Appl Stat 2012; 6(4): 1971- 

97. 

36. Di Quinzio MK, Oliva K, Holdsworth SJ, et al. Proteomic analysis and characterisation of 

human cervico-vaginal fluid proteins. Aust N Z J Obstet Gynaecol 2007; 47(1): 9-15. 

37. Rice GE, Georgiou HM, Ahmed N, Shi G, Kruppa G. Translational proteomics: developing 

a predictive capacity -- a review. Placenta 2006; 27 Suppl A: S76-86. 

38. Ahmed N, Barker G, Oliva KT, et al. Proteomic-based identification of haptoglobin-1 

precursor as a novel circulating biomarker of ovarian cancer. British Journal of Cancer 

2004; 91(1): 129-40. 

39. Rice GE, Illanes SE, Mitchell MD. Gestational diabetes mellitus: a positive predictor of type 

2 diabetes? Int J Endocrinol 2012; 2012: 721653. 

40. Salomon C, Ryan J, Sobrevia L, et al. Exosomal signaling during hypoxia mediates 

microvascular endothelial cell migration and vasculogenesis. PLoS One 2013; 8(7): e68451. 

41. Georgiou HM, Lappas M, Georgiou GM, et al. Screening for biomarkers predictive of 

gestational diabetes mellitus. Acta Diabetol 2008; 45(3): 157-65. 

42. Freedman LP, Cockburn IM, Simcoe TS. The Economics of Reproducibility in Preclinical 

Research. PLoS Biol 2015; 13(6): e1002165. 

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