Professor Kairbaan Hodivala-Dilke
Research Interests
Professor Kairbaan Hodivala-Dilke's main research themes are in: Adhesion and Integrins, Tumour Angiogenesis, Cancer Cell Biology, Metastasis and Invasion and Breast Cancer
Angiogenesis, the formation of new blood vessels from pre-existing ones, is essential for tumour growth and cancer spread. Modulation of angiogenesis is therefore a logical approach to cancer treatment. Our research aims to examine the molecular mechanisms underlying angiogenesis, vascular leakage and lymphangiogenesis, using a combination of endothelial-, pericyte and lymphatic endothelial-specific knockout and knockin systems in mouse models of cancer and other vascular diseases, and ex vivo angiogenesis assays and analysis of the cellular and molecular mechanisms behind these observations.
Our research has focused on the role of adhesion related molecules including various integrins and downstream signalling molecules in angiogenic processes. Our seminal finding that αvβ3-integrin, rather than promoting neovascularisation, actually acts as a negative regulator of pathological angiogenesis was a major conceptual advance (L.R. Reynolds et al., Nature Medicine 2002). In international collaborations this work led to further discoveries of how this, and other integrins such as a3b1 and a6b1, can also regulate angiogenesis (S.D. Robinson et al., ATVB 2004; A. Reynolds et al., Cancer Research 2004; L.R. Reynolds et al., Nature Medicine 2005, R. Silva et al., American Journal of Pathology, 2010; M. Germain et al., Journal of Pathology, 2010).
These studies also guided us to a better understanding of how low doses of αvβ3 inhibitors can upregulate angiogenesis (A. Reynolds et al., Nature Medicine, 2009). Downstream of integrins and growth factor receptors we have shown that signalling molecules such as Rac-1 and focal adhesion kinase (FAK) can also play significant roles in the regulation of angiogenesis (G. D’Amico et al., Development 2009; B. Tavora et al., EMBO Molecular Mechanisms, 2010)
More recently, we have exploited a mouse model of Downs’ syndrome to identify that 3 copies of certain chromosome 21 genes can specifically inhibit tumour angiogenesis providing us with a new system to discover novel modulators of neovascularisation (L.R. Reynolds et al., Nature, 2010).
Our overall goal is to discover novel therapeutic vascular targets to modulate blood vessel growth in the control of disease.
Profile
I joined the Tumour Biology Centre, in August 2003, as an Hon. Senior Lecturer and 6-year tenure track CR-UK employee and have since built the Cell Adhesion and Disease laboratory, funded predominantly by Cancer Research UK. I completed my PhD at the Imperial Cancer Research Fund, London in 1994, followed by a postdoctoral fellowship at MIT, Cambridge MA, USA, before returning to the UK in 1999 to start my 6-year tenure track position with CR-UK. I have set up a research programme investigating the role of cell adhesion molecules in cancer progression both in vivo and in vitro, with particular interest in skin and angiogenesis. I was granted Tenure with CRUK in 2005 and was made Professor of Angiogenesis in 2010. My future research will focus on the roles of specific integrins and other cell adhesion molecules in angiogenesis.
Funding
- 2010-2015: Cancer Research-UK Programme grant (£3,150,000)
- 2010-2013: Medical Research Council Project grant (£460,000)
- 2009-2012: Breast Cancer Campaign Project grant (£190,000)
- 2008-2012: Breast Cancer Campaign Project grant (£170,408)
- 2008-2011: CR-UK Mol Pathology PhD studentship (£120,000)
- 2008-2012: Cancer Research-UK PhD studentship (£120,000)
- 2008-2011: Cancer Research-UK Project grant (£250,000)
- 2005-2010: Cancer Research-UK Programme grant (£3,250,000)
- 2004-2008: Breast Cancer Campaign PhD studentship (£160,309)
- 2005-2008: AICR Project Grant (£188,842)
- 2003-2005: Cancer Research-UK Project Grant (£183,068)
- 2002-2005: Cancer Research-UK Postdoc Fellowship (£150,102)
Key Publications
alpha3beta1 integrin-controlled Smad7 regulates reepithelialization during wound healing in mice. Reynolds LE, Conti FJ, Silva R, Robinson SD, Iyer V, Rudling R, Cross B, Nye E, Hart IR, Dipersio CM, Hodivala-Dilke KM. J Clin Invest. 2008 Mar;118(3):965-74. PMID: 18246199
Stimulation of tumor growth and angiogenesis by low concentrations of RGD-mimetic integrin inhibitors. Reynolds AR, Hart IR, Watson AR, Welti JC, Silva RG, Robinson SD, Da Violante G, Gourlaouen M, Salih M, Jones MC, Jones DT, Saunders G, Kostourou V, Perron-Sierra F, Norman JC, Tucker GC, Hodivala-Dilke KM. Nat Med. 2009 Apr;15(4):392-400. Epub 2009 Mar 22.PMID: 19305413
Tumour angiogenesis is reduced in the Tc1 mouse model of Down's syndrome. Reynolds LE, Watson AR, Baker M, Jones TA, D'Amico G, Robinson SD, Joffre C, Garrido-Urbani S, Rodriguez-Manzaneque JC, Martino-Echarri E, Aurrand-Lions M, Sheer D, Dagna-Bricarelli F, Nizetic D, McCabe CJ, Turnell AS, Kermorgant S, Imhof BA, Adams R, Fisher EM, Tybulewicz VL, Hart IR, Hodivala-Dilke KM. Nature. 2010 Jun 10;465(7299):813-7.PMID: 20535211
Regulation of lymphatic-blood vessel separation by endothelial Rac1. D'Amico G, Jones DT, Nye E, Sapienza K, Ramjuan AR, Reynolds LE, Robinson SD, Kostourou V, Martinez D, Aubyn D, Grose R, Thomas GJ, Spencer-Dene B, Zicha D, Davies D, Tybulewicz V, Hodivala-Dilke KM. Development. 2009 Dec;136(23):4043-53. PMID: 19906871
Further Publications
For additional publications, please click here.
Research Group
The Angiogenesis Laboratory (Current Members):
- Dr Stephen Robinson: Senior Scientific officer
- Dr Louise Reynolds: Postdoctoral research fellow
- Dr Dylan Jones: Postdoctoral research fellow
- Dr Tanguy Lechertier: Postdoctoral research fellow
- Dr Bernardo Tavora: Postdoctoral research fellow
- Dr Ping Wong: Postdoctoral research fellow
- Dr Annika Alexoloupou: Postdoctoral research fellow
- Dr Isabelle Fernandez: Postdoctoral research fellow
- Ms Silvia Batista: PhD student
- Ms Marianne Baker: PhD student
- Ms Estafania: Visiting PhD Student
Past members, what they did and where they are now:
- Dr. Andrew Reynolds: Postdoctoral research fellow (2002-2008)
Now: Lab Head, Tumour Angiogenesis Group, Breakthrough Research Centre, Institute of Cancer Research, London, UK - Dr. Vassiliki Kostourou: Postdoctoral research fellow (2006-2008)
Now: Lab Head, Vascular Adhesion Laboratory, Alexander Fleming Institute, Athens, Greece. - Dr Francesco Conti: PhD student (2000-2004).
Now: Lab Head, Dubowitz Neuromuscular Centre, Institute of Child Health, University College London, UK. - Dr Rita Silva: PhD student (2004-2008).
Now: Postdoc with Prof. Janet Rossant, Hospital for Sick Children, Toronto, Canada. - Dr Gabriela D’Amico: PhD student (2004-2008)
Now: Postdoc with Prof. Kari Alitalo, University of Helsinki, Finland. - Dr Mike Germain: PhD student (2005-2009).
Now: Postdoc with Dr Julie Bastien, Novartis, London, UK. - Dr Alan Watson: PhD Studentm, CRUK Clinical Research Fellow (2005-2009)
Now: Gastroenterology Consultant, Whipps Cross Hospital, London, UK.
