MMI Clinical and Translational Research Scholars Programme ...

• Research with human subjects or onmaterial of human origin such as tissues,specimens and cognitive phenomena in theClinical Research Facilities with supportfrom translational research laboratories.Please refer to page 7-11 for a list of potentialresearch project supervisors, together with detailsof their research interests.Structure of the CTRSPPlease refer to the CTRSP timeline on page 6.Year 1 of the 4-year programme includes core andoptional graduate education modules delivered inDublin, Cork and Galway. These modules providea grounding in essential research skills andtransferable skills together with access to specialisttopics.Year 1 also features practical placements in industry,in academic research laboratories and in clinicalresearch facilities.Towards the end of the first year, MMI Clinical &Translational Research Scholars will select theirPhD projects in areas including drug discovery,discovery/validation of biomarkers and patientorientedresearch in clinical research facilities.Please refer to page 7-11 for a list of potentialresearch project supervisors, together with detailsof their research interests.In years 2 and 3, work on PhD research projectsis supplemented with access to online graduateeducation modules with a strong innovation andcommercialisation focus. Annual Scientific Meetingsprovide a forum for scholars to interact further andpresent their research.Graduate Education ModulesIn Year 1, the MMI Clinical & Translational ResearchScholars will participate in core modules at UCDand TCD and optional specialist modules in UCCand NUI Galway.Core Module topics include:• Disease Pathogenesis and the TranslationalPathway.• Molecular Medicine.• Communication, Teamwork and ResearchEthics.• Advanced Imaging.• Clinical Pharmacology.• Biostatistics.Optional Specialist Module topics include:• Early phase oncology.• Early phase clinical development.• Making clinical research change practice.• Stem cells and gene therapy.• Drug development and Clinical TrialsDesign.• Biomarker discovery in practice.• Neonatal brain injury.• Cardiovascular Biology.• Gastrointestinal Health.In Years 2 & 3 Scholars will complete distancelearning based modules.Module topics include:• IP and Technology Transfer.• Project Management.• Epidemiology.• Regulation Procedures.• Clinical Research Questions.• Case Studies in Research Ethics.• Case studies in Drug Development.• Case Studies in Biomedical DeviceDevelopment.PlacementsDuring Year 1, MMI Clinical & Translational ResearchScholars will undertake placements in academicresearch groups, in clinical research facilities, andin industry. Placements are designed to familiariseScholars with the different research environments,build links with other researchers, and enable thecompletion and reporting of concise researchprojects with the support of mentors. In addition tothe CTRSP academic partners, industry partnersinclude Amgen, Creganna-Tactx Medical, MerrionPharmaceuticals, Medtronic, Opsona, and Pfizer.Research CentresNUI GalwayNational Centre for Biomedical Engineering Science(NCBES)The NCBES at NUI Galway is an interdisciplinarycentre which brings together scientists, engineers,information technologists and clinicians in a teambased,problem-centred approach to research.The Centre’s research is focused on innovativetherapeutic solutions to current medical challengesincluding cardiovascular disease, orthopaedics,reproductive medicine and cancer.3

Regenerative Medicine InstituteThe Regenerative Medicine Institute (REMEDI) wasestablished at NUI Galway in 2004 as a ScienceFoundation Ireland funded Centre for Science,Engineering and Technology with a central focuson the development of novel therapies for treatingmajor human diseases involving adult stem celltherapy and gene therapy.NUI Galway Clinical Research FacilityThe NUI Galway Clinical Research Facility, fundedby the Health Research Board and the HealthService Executive, opened in 2008. A new purposebuiltfacility is due to open on the campus ofUniversity Hospital Galway. This joint clinical andtranslational research centre will comprise state-ofthe-artfacilities for patient-based research and forthe processing and analysis of biological specimenssuch as blood samples from those patients.Trinity College DublinInstitute of Molecular MedicineThe Institute of Molecular Medicine (IMM) wasestablished in 2003 as a state-of-the-art facilitywithin the Trinity Centre for Health Sciences atSt James’s Hospital. The IMM is dedicated toresearch into the molecular basis of human diseasewith significant core technology platforms in HighContent Screening Analysis, Cell Signalling, HighThroughput Genomics, and Transcriptomics. Keyresearch themes are Infection & Immunity, Cancerand Neurosciences.University College CorkUCC BioSciences InstituteBasic and translational research at UCC havebeen greatly enhanced by the opening, in 2002,of the Biosciences Institute (BSI). The Instituteincorporates six major research programmes:Neuroscience, Cancer Biology, Cell Signalling andCardiovascular Health, Plant Biotechnology andIntegrative Genomics, Food for Health and MicrobeHost Interaction.UCC Clinical Research FacilityA Clinical Research Facility funded by the HRB, HSEand UCC is being established at Cork UniversityHospital (children) and at the Mercy UniversityHospital (adults). The Clinical Research Facility willfacilitate the development of exciting new strategiesin partnership with UCC and affiliated hospitals andwith food and pharmaceutical industries to producenew treatments for patients across a large range ofclinical disorders.University College DublinDublin Academic Medical Centre (DAMC)UCD Clinical and Translational Research spansfrom, The Conway Institute of Biomolecularand Biomedical Research at Belfield across theDAMC, including St. Vincent’s University Hospital(SVUH) and The Mater Misericordiae UniversityHospital (MMUH). The integrated facilities featurea multidisciplinary Biomedical research Institutewith over 550 active research staff from across theuniversity and its associated teaching hospitals. TheUCD Clinical Research Centre (CRC) is located atthe two University Hospital sites SVUH and MMUHin purpose-built facilities supporting principalinvestigators involved in investigator-lead clinicaltrials, industry-sponsored studies and providesresearchers with research nursing services, datamanagement and biobanking facilities. The majorfocus of translational biomedical research at UCDincludes Inflammation, Infection, Immunity & Repair,Diabetes & Vascular Biology and Neuroscience.Dublin Centre for Clinical Research (DCCR)The DCCR, funded by the HRB and Wellcome Trust,will provide the infrastructure – the physical space,facilities and trained staff – needed to supportcollaborative clinical research studies across Dublin.As well as building a new Clinical Research Centreat St James’s Hospital, the DCCR is networking theresearch activities taking place at the RCSI ClinicalResearch Centre at Beaumont Hospital and theUCD CRC at Mater Misericordae University Hospitaland St. Vincent’s University Hospital into a facilityfor multi-centre clinical studies.CTRSP Application ProcedureTwenty scholarships are available in the first year ofthis prestigious national programme coordinated byMolecular Medicine Ireland. Scholars will be basedin one of the participating academic institutions:NUI Galway, TCD, UCC and UCD. Applicants arerequested to indicate their preferred host institutionin the application form.Scholarships include a stipend of €16,000 perannum for four years and an allowance for researchand travel expenses. Fees for EU students areincluded.High-calibre candidates holding, or expecting toreceive, a first-class or upper second-class honoursdegree in an appropriate discipline are encouragedto apply.Further details and application form are available at:www.molecularmedicineireland.ie/ctrsp5

MMI Clinical & Translational Research Scholars ProgrammeTimelinePhD completedSelect PhDprojectCore ModulesAcademic Lab,Industry and ClinicalResearch FacilityPlacementsAnnual ScientificMeetingAnnual ScientificMeetingOnline ModulesAnnual ScientificMeetingAnnual ScientificMeetingSpecialist ModulesPhD projectOctober2011Year 1October2012Year 2October2013Year 3October2014Year 46

CTRSP Investigators and Research ProjectsPotential research project supervisors in NUI Galway, Trinity College Dublin, University CollegeCork and University College Dublin are listed here with details of their research interests. Thislist is intended to give candidates examples of the areas of research that will be available to MMIScholars during laboratory rotations in Year 1 and when the PhD project is selected towards theend of Year 1. Please note that Principal Investigators and areas of research listed here are forguidance. Some projects listed here may not be available and others may be included at the timeof project selection.NUI GalwayPrincipal InvestigatorProf Laurence EganProf Frank BarryProf Martin CormicanProf Fidelma DunneProf Matt GriffinProf Michael KerinProf John LaffeyProf Andrew MurphyProf Tim O’BrienDr Eilis DowdProf Michael O’DwyerResearch InterestsMolecular mechanisms of intestinal injury, repair and carcinogenesis; focus on biologicalfunctions of transcription factor NF-kappaB; identification and characterization of noveltherapeutic targets for inflammatory bowel disease, colon cancer and radiation injury to theintestinal tract; Clinical Research.Isolation, characterization and therapeutic application of adult stem cells from bone marrow;cardiovascular and arthritic diseases; use of Mesenchymal Stem Cells for the delivery ofspecific therapeutic genes; proteomics and mass spectrometry for the identification of surfacemolecules on cells.Clinical Microbiology; prevention, diagnosis and management of infectious disease; MRSA;antibiotic resistance; Salmonella Reference Laboratory.Endocrinology; pregnancy and diabetes; ATLANTIC DIP programme which is a prospectivestudy to examine the outcome of pregnancy in diabetic women.Immunology of Acute Kidney Injury; Immunological Properties of Mesenchymal Stem Cells;Immunomodulatory Effects of Vitamin D; Pathogenesis of Kidney Transplant Fibrosis; ClinicalOutcomes of Kidney Transplantation; Polyomavirus-associated Nephropathy.Gene Expression Profiling investigating the metastatic potential of early breast cancerusing a combined gene expression microarray and real-time quantitative PCR approach;Gene Therapy investigating the potential of human Mesenchymal Stem Cells as vectors fortherapeutic gene delivery to breast tumours; Population Genetics to identify common genesthat predispose to breast cancer.Hypercapnic acidosis; gene and stem cell therapies in the setting of Acute Respiratory DistressSyndrome; effects of sepsis on myocardial performance and on mitochondrial bioenergetics,effects of volatile anaesthetic agents and of sidlenafil in the Foeto-Placental Circulation;provision of effective analgesia for acute pain.General Practice; chronic disease management and professional practice in the community;Ambulatory Blood Pressure Monitoring, Secondary Prevention of Heart Disease in GeneralPractice; antibiotic resistance.REMEDI; gene delivery and stem cell biology to promote organ regeneration and repair;ischaemic cardiovascular disease and osteoarthritis; targeted expression of nitric oxide geneisoforms in the diseased vessel site and the use of endothelial progenitor cells as a genedelivery system; pathogenesis of diabetic vascular disease including the role of endothelialprogenitor cell dysfunction.The development and validation of novel cell and gene therapies for Parkinson’s disease;using viruses to deliver therapeutic gene products to the brain; transplantation of dopaminergicneurons derived from human embryos, xenodonors or stem cells.Development of new therapeutic approaches for the treatment of leukaemia and multiplemyeloma; Cdc7 inhibition in chronic lymphocytic leukaemia (CLL) and myeloma; BH3 mimeticsand TRAIL as apoptosis inducing agents in leukaemia; clinical trials and translation.7

Dr Fabio QuondamatteoProf Lokesh JoshiDr Karl McCullaghDr Francis FinucaneProf Rob WoodsProf Richard FlavinDr Howard FearnheadDr Thomas KropmansProf Peter DockeryDr John LynchDr Faisal SharifProf Corrado SantocanaleDr Mary MurphyDr Leo KevinDr Paul DonnellanProf John MorrisonProf Frank GilesDr Malini OlivoDr Mark da CostaStudy of the cell biological role of basement membrane and extracellular matrix componentsin vivo; Glycoscience; Cell biological aspects of normal and pathological development; ClinicalAnatomy; development of therapeutic devices for neuromuscular stimulations.Glycosciences and Bioengineering to discover and develop novel molecules, processesand biomaterials and relevant technologies for biotherapeutic and biodiagnostic purposes;Post-translational modifications and recombinant protein engineering; protein and peptidetherapeutics; glycosensors, glycosignatures, and glycomimetics.Muscular Dystrophy; Proteins associated with the dystrophin protein complex; Cell signallingand regulation of skeletal muscle fibre types; Growth and regeneration of muscle.Endocrinology; Obesity; Bariatric Medicine; Diabetes.Relationships between the conformations of carbohydrate molecules and biologicalrecognition and activity, particularly the mechanisms involved in carbohydrate recognitionin immunological events; computational techniques of molecular dynamics and free energyperturbation simulations; examinations of bacterial antigen-antibody interactions, as well ascarbohydrate-lectin interactions.Molecular mechanisms of breast cancer; breast cancer progression and heterogeneity;evaluation of different stages of the disease from early precursor lesions through in situtumours to invasive disease and metastasis.Biochemical and molecular basis of apoptotic cell death; Neurological Disorders, CardiovascularDisease, and Cancer with the aim of developing new therapies for these diseases.Postgraduate medical education and continuing professional development; application ofinformation and communication technologies to support evidence practice in both hospitaland community based health care.Neurobiology; Cellular interactions in the developing and ageing nervous system; Developmentand repair of the Spinal Cord; Human Reproduction; Structure-Function of the HumanEndometrium; Cellular effects of endocrine disrupting chemicals on reproductive tissues;Feto-maternal interface.Genetics of epilepsy predisposition; pharmacogenetics of anti-epileptic drug response;genetics of Parkinson’s disease; psychosocial impact of epilepsy.Vascular biology and Gene Eluting Stents; translational medicine focusing on cardiovascularclinical trials for medical devices and basic science outputs; myocardial regeneration.DNA replication and cell cycle progression; developing novel therapeutic strategies andmolecular biomarkers to follow drug action in cancer patients; molecular characterization ofCdc7 kinase and of its substrates and defining the mechanism of action of emerging Cdc7inhibitors.Adult stem cells for tissue regeneration in cartilage repair and osteoarthritis; Biology of vascularderived stem cells in atherosclerosis; Cardiomyogenic differentiation of adult stem cells; Effectof electroactive particles.Effects of sepsis on myocardial performance and on mitochondrial bioenergetics, volatileanaesthetic agents and sidlenafil in the Foeto-Placental Circulation.Medical Oncology; Extensive-Stage Small Cell Lung Cancer; Clinical Trials; national breastcancer trials; radiation oncology.Myometrial physiology; Pre-term labour; Pre-natal diagnosis and high-risk obstetrics; volatileanaesthetic agents in the Foeto-Placental Circulation.Clinical Research; therapy for patients suffering from treatment-resistant or refractory cancer;development of novel drugs, immunotherapies, and other highly targeted approaches,including cancer-directed viruses.Molecular Imaging and Photomedicine; nano-biophotonics science for biomedical diagnosticsand therapeutics; early detection of cancer using novel minimally invasive endoscopic opticaltechniques and for the treatment of cancer using light activation of drugs that target cancer.Cardiothoracic Surgery.8

Prof Colm McDonaldDr David FinnProf Anthony WheatleyDr Donald BlackProf W.J.M. van der PuttenDr Kilian WalshDr Donal ReddanDr John KellyClinical research in psychiatry; Aetiopathogenesis of psychotic illness; Mapping of brainabnormalities associated with psychotic and affective disorders; The relationship of such brainabnormalities to genetic and environmental risk factors; effect of psychotropic medications;Endophenotypic markers of schizophrenia and bipolar disorder; Neurobiological abnormalitiesassociated with psychotic and affective disorders.Neurochemical, neuroendocrine and molecular mechanisms underlying pain, anxiety anddepression. Neuropharmacology of cannabinoid and opioid receptors. Imidazoline bindingsites, brain monoamines and the stress response. Neuroimmune mechanisms of relevance topain, inflammation and mood disorders.Control of preimplantation embryo growth and development; Mechanisms regulatingovulation; Signalling systems involved in the control of cell differentiation; Neuropharmacologyand neurotoxicology of the polyamines; pathophysiology of stroke and Parkinson’s disease;neurodevelopment in vitro models.Clinical Research; Trialynx, Inc.; cardiovascular disease including atherosclerosis anddyslipidemia; Medical diagnostics; Molecular imaging; Pediatrics.General Application of Physics and Technology in Medicine; Radiobiological modelling ofradiotherapy; Optimisation in Diagnostic Radiology; Risk and Safety with medical devices.Urology; prostate and kidney cancer.Chronic Kidney Disease and Cardiovascular risk; Contrast induced acute Kidney Injury;Anemia of Chronic Kidney Disease.Investigation of the mechanism of action of antidepressants and the development of noveltargets using animal models; the effects of antidepressants on modulating immune responses;development of nonanimal alternatives for toxicological assessment of drugs.Trinity College DublinPrincipal InvestigatorProf Dermot KelleherProf Padraic FallonProf Joseph KeaneDr Aideen LongDr Aiden CorvinProf Thomas FrodlProf Michael GillProf Alan IrvineDr Ross McManusResearch InterestsDevelopment of novel therapeutics for oesophageal cancer; the biology of the gastrointestinalimmune system.Immunological mechanisms of suppression of inflammatory diseases; study of genetic versusenvironmental predisposition to inflammatory disease; use of mouse transgenics to dissectimmune function.Translating improved understanding of pulmonary immunology into new treatments, tests andvaccines for tuberculosis. Cellular and clinical immunology.Molecular mechanisms of the inflammatory response: T lymphocyte migration – protein KinaseC (PKC): cytoskeletal interactions; genome-wide siRNA screen of T lymphocyte migration;effect of bile acids on PKC signalling in colonic and oesophageal cells.Genomics of psychosis, psychiatric disorders and cognition; targeting molecular mechanismsfor therapeutics in psychiatry/cognition.Neuroimaging: investigation of mood disorders, dementia, and schizophrenia with functionaland structural imaging techniques; use of imaging to identify markers for the prediction oftreatment response and for therapy success; genetic effects on function and structure inimaging; neurobiological underpinnings of psychiatric diseases.Relationships between phenotype and genotype in three key neuropsychiatric disorders:Psychoses, Autism and ADHD; gene hunting, functional genomics; translation of geneticfindings into clinical relevance; understanding gene function as a prelude to new treatments.Genetic and clinical studies on eczema and atopic dermatitis.Genomics of coeliac disease; gene expression in sepsis; genomics of inflammatory boweldisease.9

Dr Joe MeaneyProf John O’LearyProf Yuri VolkovProf John ReynoldsHigh resolution whole body structural imaging for cardiovascular disease and cancer; functionalimaging of tumours with high-resolution 3T MRI compared to PET-CT scanning; imaging ofatherosclerosis with high-resolution 3T MRI.Cancer stem cell biology; tumour transcriptomics; miRNA / naturally occurring anti-sensemolecules.Biomedical applications of nanotechnologies; cell adhesion and migration in inflammation andcancer; intracellular signalling and cytoskeletal dynamics; live cell and molecular imaging.Upper gastrointestinal cancer surgery: molecular predictors of sensitivity and resistance toneoadjuvant chemoradiotherapy in oesophageal adenocarcinoma; gastrointestinal mucosalimmunology; cellular and molecular studies in Barrett’s oesophagus.University College CorkPrincipal InvestigatorProf. David KerinsProf. Noel CapliceDr John CryanProf. Timothy DinanDr Liam FanningProf. Gerald Fitzgerald / Dr PaulO’TooleProf. Jonathan HourihaneProf. Edward JohnsProf. Louise KennyProf. Rosemary O’ConnorProf. Gerry O’SullivanProf. Ivan PerryProf. Eamonn QuigleyDr Anne Moore / Dr ConorO’MahonyDr Declan SodenProf Helen Whelton / Dr Cian ÓMathúnaDr Geraldine Boylan Dr DeirdreMurray / Prof Louise KennyDr Deirdre Murray / Dr MaireadKielyResearch InterestsPlatelet function and vascular diseaseStem cells and cardiovascular diseaseMolecular basis of stress induced effects on the brainStress biology, neuro gastroenterologyMolecular diversity of Hepatitis C, Human Immunodeficiency Virus and Hepatitis B Viruseand how this impacts on disease outcomeComponents of the human gut microbiota and their contribution to intestinal healthThe effect of antenatal and post natal body composition on metabolic status and metabolicrisk factors in children aged 2 and 5 years oldNeuro-humoral control of the kidney and the impact on blood pressure controlUse of metabolomic technology to search and validate early pregnancy biomarkers ofadverse pregnancy outcome; Vascular physiology/biology based programme usinga variety of animal models and ex vivo human tissue to search and characterise noveltherapeutic targets for preeclampsiaUnderstanding and overcoming resistance to therapies that target tyrosine kinasepathways in cancerCancer researchMetabolism and disease with a focus on CVD and Diabetes including biomarkers of lipidmetabolism and inflammationHost-microbiota interactions in gastrointestinal disorders.The application of Micro needles in diagnostics, therapeutics and vaccinesCancer Gene Therapy for Lung CancerDevelopment of in-situ models for clinical testing of innovations in oral health careproducts. Collaboration with the Microelectronics Applications Integration Group, TyndallNational InstituteValidation of early placental and serum biomarkers in neonatal brain injury.Cardio-metabolic phenotyping in toddlers: body composition and metabolic profiles at 2years.10

University College DublinPrincipal InvestigatorProf Dolores CahillResearch InterestsBiomarker Discovery and Validation/Qualification, Development of Diagnostic Assays; Technologydevelopments towards improved interaction screening, e.g. nanoparticles, proteins, etc.Dr Paul CrosseyThe role of insulin-like growth factors and their binding proteins in disorders of growth and metabolism.Prof Catherine GodsonProf Pat GuiryProf Michael KeaneProf Ulla KnausDr Patrick MallonProf Ken McDonaldProf Paul Mc LoughlinDr Louise RainfordProf Kieran SheahanDr Albert SmolenskiProf Douglas VealeProf R William WatsonNovel mediators of inflammation and repair in diabetic complications.Synthetic chemistry; asymmetric catalysis, medicinal chemistry, total synthesis, natural productisolation, purification and biological evaluation.Vascular remodeling - mesenchymal and progenitor cells in lung injury.Innate and mucosal immunity; Regulation of inflammation activation; Novel NADPH oxidases inhealth and disease.HIV and bone mineral density, anti-retroviral adipose tissue toxicity.Active clinical programme in area of ventricular dysfunction (4000 patient data base) with linkedlaboratory work investigating mechanisms, markers and possible novel therapeutic approaches toventricular dysfunction.Hypoxia-mediated inflammation, pulmonary hypertension and vascular remodelling.Dose Investigation and Optimisation of Practice in Diagnostic Imaging: Interventional,Mammography, RNI and CT examinations. Visualisation, segmentation and quantification studies:Ultrasound Images for Foetal Abnormalities; MR Imaging of HIV associated Lipodystrophy; MRImaging of rheumatoid and psoriatic arthritis.Prognostic & predictive markers in colorectal cancer; Familial gastrointestinal cancer. Applicationof Immunohistochemical & Molecular Genetic Techniques in Pathology. The pathobiology ofinflammatory bowel disease.Identification and characterisation of new molecules of functional importance in regulating plateletfunction.Inflammatory mediators as targets for development of novel Biopharmaceuticals using Imageanalysis assessment.Cancer target identification and biomarker discovery.The MMI Clinical & Translational Research Scholars Programme is funded under the Programme for Research in ThirdLevel Institutions (PRTLI) Cycle 5.11

February 2011