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- Professor of Molecular Cell Biology
- Metabolism & Experimental Therapeutics
- Div of Medicine
- Faculty of Medical Sciences
I undertook my undergraduate (BSc Hons) and postgraduate (PhD) studies at the University of Bristol UK in Pharmacology and Molecular/Cellular Biology respectively, where I was awarded the first BRACE (Bristol Research into Alzheimer’s Disease and Care of the Elderly) PhD studentship. During my PhD studies, I became fascinated in how cells mediate appropriate intracellular signals that enable them to survive or die depending on the environmental stimulus. This is particularly important during development (e.g. in the central nervous system) or in disease (e.g. cancer, cardiovascular disorders). During my PhD, I worked on a novel family of tyrosine receptor kinases (TRKs) which we cloned and characterised in human brain (1994). Upon obtaining my PhD, I moved to the United States to pursue my postdoctoral training at the National Cancer Institute (NCI-FCRDC, Frederick, Maryland). First, under the supervision of David Kaplan, I continued my to work on TRKs and made several key discoveries on the role of TRK-mediated survival via the PI3K signalling pathway (1998-1999). However, it was not clear at that time, precisely how the emerging cellular pro-survival signalling pathways (such as the PI3K-Akt/PKB signalling pathway) cross-talked to the apoptotic machinery. Subsequently, under the supervision of Karen Vousden, I worked on the tumour suppressor protein p53 and its regulator HDM2. During this period, I made several key discoveries on the regulation of p53 stability and activity by phosphorylation and on mechanisms of HDM2 nucleolar sequestration (1998-2000). In addition, I discovered that the PI3K-Akt/PKB pathway interfaced directly with the p53/HDM2 apoptotic machinery at the level of AKT/PKB and HDM2, and I identified HDM2 as a novel substrate for AKT/PKB phosphorylation in response to survival signals (2002). This latter post was supported by the Human Frontier Fellowship Program. In addition, I was awarded three young investigator awards for my postdoctoral studies while at NCI-FCRDC (1997, 1998 and 1999). During the last year of my postdoctoral work, I became interested in hypoxia signalling and the hypoxia inducible factor (HIF) family of transcription factors (2000).
In 2001, I moved back to the UK to set up my group at The Institute of Cancer Research (ICR). Working on the regulation of HIF signalling as a basis for the development of strategies to identify novel therapies for cancer treatment within the CR-UK Cancer Therapeutics Unit at The ICR I was able to combine my basic research with multidisciplinary drug development. During this period (2002-2007) my group made several important discoveries in the HIF/hypoxia arena. In particular, my group discovered that HIF is responsive to growth factors and oncogenic signals (2004-2007) and we identified a reciprocal relationship between the HIFs (2006). In addition, my group identified and developed novel small molecule inhibitors of the HIF pathway. In 2005, I was awarded an EACR Young Investigator Award (highly commended) for my work in the HIF/hypoxia arena. We also, made novel discoveries relating the mechanistic relationship between p53/HDM2 and HIF in hypoxia (2004 and 2009).
In Oct 2007, I was recruited to Imperial College London as a Reader in Cancer Biology and I received an honorary appointment at The ICR. In 2008, I moved my group to University College London (UCL) to set up and co-Direct the Centre for Cell Signalling and Molecular Genetics (CSMG) within the Division of Medicine. The Division of Medicine at UCL offers a multidisciplinary state-of-the-art research environment. In addition, I am an affiliated Principal Investigator with UCL Cancer Institute and UCL/KCL Comprehensive Imaging Centre. In 2011, I was elected as a Fellow of the Society of Biology (FSB) for my contribution to the biological sciences.
My research programme primarily focuses on elucidating the key signalling mechanisms regulating the hypoxia inducible factor (HIF) pathway as a basis for gaining a better understanding of the role of HIF in disease (e.g. cancer, renal and cardiovascular diseases, and stroke) and translating our basic research findings by identifying novel therapeutics that target the HIF pathway.
2010-current: CR-UK Centre PhD Programme (Cancer Biology, Translational Research, Experimental Cancer Therapeutics, and Clinical Cancer Studies), UCL Cancer Institute, UCL; primary supervisor
2009-current: MSc Clinical and Experimental Medicine, UCL. ‘Targeting the hypoxia-inducible factor pathway as a new therapeutic approach to cancer treatment’ seminars; primary supervisor
2009-current: MSc Cancer Course, UCL. ‘Hypoxia signalling in cancer’ seminars
2009-current: PhD Programme in Drug Discovery, UCL; co-supervisor
2009-current: BHF PhD Programme in Cardiovascular Biomedicine, UCL; primary supervisor
2007-2008: MSc Medical Oncology Course, ICR. ‘Hypoxia and angiogenesis’ seminars
|2010||Affiliated Principal Investigator||Cancer Research UK and UCL Cancers Centre,||UCL Cancer Institute, University College London, United Kingdom|
|2009||Affiliated Principal Investigator||Comprehensive Cancer Centre||King’s College London/University College London , United Kingdom|
|FEB-2008||Reader in Cancer Biology and co-Director, CSMG||Medicine||University College London, United Kingdom|
|OCT-2007 – JAN-2008||Reader in Cancer Biology||Medicine||Imperial College London, United Kingdom|
|DEC-2000 – OCT-2007||Group Leader||Cancer Research UK Centre for Cancer Therapeutics||Institute of Cancer Research, United Kingdom|
|JAN-1997 – NOV-2000||Senior Postdoctoral Researcher (Human Frontiers Fellowship)||Molecular Carcinogenesis Section||NCI-FCRDC, Frederick MD, United States|
|MAY-1995 – DEC-1996||Postdoctoral Researcher||Eukaryotic Signal Transduction Section||ABL Basic Research Program, NCI-FCRDC, Frederick MD, United States|
|1995||PhD||Doctor of Philosophy||University of Bristol|
|1991||BSc Hons||Bachelor of Science (Honours)||University of Bristol|