biomedical sciences research institute - Research - University of Ulster

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Professor Stephanie McKeownProfessor of Cancer BiologyContact Details:T: +44 (0)28 70323542sr.mckeown@ulster.ac.ukProfessor McKeown’s main area of interest is tumour biology with particular reference to hypoxia and bioreductivedrugs, and their combination with radiotherapy and chemotherapy.Tumour hypoxia is a critical feature of many solid tumours and is known to reduce the efficacy of both radiotherapyand chemotherapy. Bioreductive drugs are designed to specifically target hypoxic cells and can be used to treat solidtumours to enhance the effects of standard therapies. This class of cytotoxic agent is particularly useful as it is designedto be administered as a non-toxic prodrug. It becomes cytotoxic in hypoxic cells and therefore causes limitedsystemic toxicity since the cytotoxic species is only produced in areas of hypoxia i.e. primarily in tumours. In collaborationwith Professor LH Patterson (Director, Institute of Cancer Therapeutics, University of Bradford) our work hasdemonstrated that AQ4N (Banoxantrone) is the best bioreductive drug available. Pre-clinical studies carried out atthe University of Ulster have provided convincing evidence of the efficacy of AQ4N and further supporting evidencehas come from several other groups world-wide. Clinical trials of AQ4N combined with radiotherapy and chemotherapyare ongoing in both the UK and USA (reviewed in an invited paper indicated below).This year we have identified novel responses to the treatment of tumours which indicate that we need to moreclearly understand what occurs in the initial days after treatment with a number of drugs. There are several consequencesof these studies which are currently not clearly recognised in the scientific community. We plan to use ourknowledge to develop new ‘informed schedules’ and test them for efficacy. In addition we plan to follow the biological/ molecular consequences of these changes. A greater understanding of these changes could lead to the design ofmore effective ways to eradicate solid tumours.Professor McKeown is currently the University of Ulster’s Designated Individual (DI) as described under the HumanTissue Act (2004). In this capacity she oversees all of the activities relating to storage and use of human tissues usedprimarily for research within the University and its associated sites. She is also the Chairperson of the Irish RadiationResearch Society (and co-organiser of its scientific meeting in Dublin, October 2007) and a member of: the BritishInstitute of Radiology (and its Cancer and Radiation Biology Committee); the National Cancer Research Institute,UK (and its Radiotherapy Trials Clinical Studies Group); the Council of the International Association for RadiationResearch; the Ireland-Northern-Ireland-NCI-USA Cancer Consortium (and the Scientific Committee for its biennialmeeting in Dublin, 2008).Professor McKeown has been the Chairperson of the Northern Ireland (NI) Cancer Recognised Research Groupsince 2007 as well as being the Treasurer to the NI Committee of the Institute of Biology since 2004. She has alsoacted as Radiobiology specialist examiner, for the Clinical Oncology examinations at the Royal College of Radiologistsin London and became an External Assessor for the University of Malaya, Kuala Lumpar in 2008.Publications:Butterworth KT, McCarthy HO, Devlin A, Ming L, Robson T, McKeown SR, Worthington J; Hypoxia selects for androgenindependent LNCaP cells with a more malignant genotype and phenotype; International Journal of Cancer, 123: 760-768, 2008O’Keeffe MB, Devlin AH, Burns AJ, Gardiner TA, Logan ID, Hirst DG, McKeown SR; Investigation of pericytes, hypoxiaand vascularity in bladder tumours: association with clinical outcomes; Oncology Research, 17: 93-101, 2008O’Rourke M, Ward C, McKenna J, Worthington J, Valentine A, Hirst DG, McKeown SR; Evaluation of the anti-angiogenicpotential of AQ4N; Clinical Cancer Research, 14: 1502-1509, 200834
Devlin AH, McIlroy M, McKeen HD, Bonde P, Menezes AAC, Bell Z, Swarbrick CJ, Robson T, DG Hirst, Campbell FC,McGuigan JA, McKeown SR; Cytochrome P450 1B1 expression in rat oesophageal tumorigenesis promoted by gastricand duodenal reflux; Molecular Carcinogenesis [Jul 10, Epub ahead of print] 2008Invited peer reviews:McKeown SR, Cowen RL, Williams KJ; Bioreductive Drugs: from Concept to Clinic; Clinical Oncology, (Royal Collegeof Radiologists), 19: 427-442, 2007McKenna DJ, McKeown SR, McKelvey-Martin VJ; Potential use of the comet assay in the clinical management of cancer;Mutagenesis, 23(3): 183-190, 2008Dr Christian HölscherSenior Lecturer in NeurobiologyContact Details:T: +44 (0)28 70324178christian_holscher@mac.comDr Hölscher’s main research interest is in Alzheimer's Disease. Alzheimer’s is a neurodegenerative disease that increasinglyaffects the population of industrialized countries. One of its hallmarks is the appearance of amyloid proteinaggregates in the brain. Currently, the cellular mechanisms of Neurodegeneration induced by different amyloid fragmentsare under intense investigation. Using the techniques of in vivo recording of neuronal activity, a battery of differentlearning tasks, and histological analysis, the short- and long-term effects of amyloid peptides (the peptide thataggregates in the brains of Alzheimer patients) are analysed. One project focuses on the analysis of transgenic animalsthat over-express the human form of amyloid precursor proteins.The neurodegenerative effects of amyloid fragments activate a cascade of biochemical processes that eventually leadto cell death. Key processes in this cascade include the increased calcium influx into neurons via ion channels, theactivation of enzymes that produce free radicals, and the induction of auto-inflammatory responses.Several strategies to identify and block these processes are in progress. Collaborations with the Univeristy’s DiabetesResearch Group to develop novel neuroprotective peptides are underway. They have developed novel proteaseresistantinsulin-like incretin analogues intended to treat patients with Type 2 Diabetes, but that also have growthfactor-like properties in the brain and are very promising in preventing neurodegeneration induced by amyloid fragments.A number of novel incretin analogues have been tested in different mouse models of Alzheimer’s disease andhave shown very promising effects.During the period under review, Dr Hölscher continued to manage a pilot project grant (£17,000) from the AlzheimerResearch Trust for the “Analysis of novel GLP-1 agonists on neuronal survival”; as well as continuing to manage35
Page 1: BIOMEDICAL SCIENCESRESEARCH INSTITU
Page 4 and 5: 1 Foreword by the Pro Vice-Chancell
Page 6 and 7: 2 Foreword by the Research Institut
Page 8 and 9: The BMSRI Research StructureThe BMS
Page 10 and 11: BMSRI Core FacilitiesContact: Karen
Page 12 and 13: of Metabolomics, pharmacy, nutritio
Page 14 and 15: BMSRI Academic Heads new Regional N
Page 16 and 17: 4. BIOMEDICAL GENOMICS RESEARCH GRO
Page 18 and 19: Recent Funding Initiatives:C-TRIC:
Page 20 and 21: Dr Mateus Webba da SilvaLecturer in
Page 22 and 23: 5. BIOIMAGING RESEARCH GROUPResearc
Page 24 and 25: developmental alterations that mani
Page 26 and 27: Publications:Bigot S, Lucas L, Morr
Page 28 and 29: Publications:Barnes CA, O’Hagan B
Page 30 and 31: We also measure the genotoxic effec
Page 32 and 33: 6. CANCER AND AGEING RESEARCH GROUP
Page 34 and 35: Professor Anthony P McHaleProfessor
Page 38 and 39: an Alzheimer Research Trust collabo
Page 40 and 41: JM, Waugh DJJ; Dexamethasone potent
Page 42 and 43: have wider applications in vivo, in
Page 44 and 45: Inter-relationships between diet an
Page 46 and 47: Flatt PR; Effective surgical treatm
Page 48 and 49: These areas are the subject of seve
Page 50 and 51: Dr YHA Abdel-WahabSenior Lecturer i
Page 52 and 53: Dr VA GaultLecturer in Molecular Bi
Page 54 and 55: McClean PL, Irwin N, Hunter K, Gaul
Page 56 and 57: Publications:Duffy NA, Green BD, Ir
Page 58 and 59: 8. MICROBIOLOGY AND BIOTECHNOLOGYRE
Page 60 and 61: Publications:Graham RJL, Graham C,
Page 62 and 63: analyses. However there is still a
Page 64 and 65: Plessas S, Bekatorou A, Koutinas AA
Page 66 and 67: Biochemical studies/ viral evasion
Page 68 and 69: Dr Stephen McCleanLecturer in Prote
Page 70 and 71: environmental remediation and as ro
Page 72 and 73: 9. NORTHERN IRELAND CENTRE FOR FOOD
Page 74 and 75: 26-28 Sept 2007: International Seaf
Page 76 and 77: Dr Barnes has developed expertise i
Page 78 and 79: Dr Alison GallagherSenior Lecturer
Page 80 and 81: In addition, results of a pilot stu
Page 82 and 83: Dr Maeve KerrResearch AssociateCont
Page 84 and 85: Memberships of External Committees/
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Indicators of Esteem:Professor McNu
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were examined. The intervention and
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Within this work both short-term an
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micronutrient supplementation at a
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10. STEM CELL & EPIGENETICS RESEARC
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Publications:Lees-Murdock DJ, Lau H
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Publications:Lees-Murdock DJ, Lau H
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11. SYSTEMS BIOLOGY RESEARCH GROUPT
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Kravtsov V, Swain M, Schuster A, Du
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Dr Daniel BerrarLecturer in Biomedi
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Zhang et al; Incorporating Feature
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Bala P, Baldridge K, Benfenati E, C
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In addition there is a growing them
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Clinical work involves development
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In 2009 he was appointed Chairman o
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Stevenson TR, Goodall EA and Moore
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Dr Raymond BeirneLecturer in Optome
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Dr Julie McClellandLecturer in Opto
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Graham JE, Moore JE, Moore JE, McCl
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Research Staff:Dr David OrrSenior R
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Dr Victoria McGilliganResearch Asso
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13. Externally Funded Projects duri
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Grant Holder Anderson, Prof RSFundi
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Funding Body Royal Irish AcademyAmo
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14. BIOMEDICAL SCIENCES RESEARCH IN
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Student: Simon GenglerTitle: Effect
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Student: Anisha MazumdarTitle: Anal
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Student: Clare RyanTitle: How does
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CONGRATULATIONS TO THE FOLLOWING PO
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