Professor Kairbaan Hodivala-Dilke
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 cell type-specific knockout and knockin systems in mouse models of cancer and other vascular diseases (endothelial-, pericyte and lymphatic endothelial), 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 α3β1 and α6β1, 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 also play a significant role in the regulation of angiogenesis (G. D’Amico et al., Development 2009).
Additionally, 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).
Most recently we are keen to understand the role of stromal focal adhesion kinase (FAK) not only in tumour growth and progression but also in chemoresistance (Tavora et al., EMBO Molecular Mechanisms, 2010). This work is ongoing.
Our overall goal is to discover novel therapeutic vascular targets to modulate blood vessel growth in the control of disease.
I started my scientific career as a technical assistant, first at The Jodrell Laboratories, Kew Gardens, and then in the Wellcome Trust funded Malaria Research team at Imperial College, London. These short tastes of a scientist’s life fueled my enthusiasm to embark on a career in research.
Following my undergraduate studies at the University of Southampton (1994) I gained a PhD after studying epithelial cell biology with Professor Fiona Watt at The Imperial Cancer Research Fund. I undertook postdoctoral work with Professor Richard Hynes at The Massachusetts Institute of Technology, USA, where my experience in using genetically modified mice began.
I then returned to the UK and was an Imperial Cancer Research Fund tenure-track fellow with Professor Ian Hart, first at St. Thomas’ Hospital and later here at Barts Cancer Institute, Barts and The London School of Medicine and Dentistry. I was awarded tenure in 2004 and became Professor of Angiogenesis in 2009. I now also stand as Deputy Director of the Barts Cancer Institute since 2012. Our research is dedicated to investigating the molecular basis of angiogenesis and tumour growth.
Last five years
- 2012-2015 Association of International Cancer Research (£260,803)
- 2011 Cancer Research-UK Large Equipment (£200,000)
- 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 Cancer Research-UK Molecular 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)
Reynolds LE, Wyder L, Lively JC, Taverna D, Robinson SD, Huang X, Sheppard D, Hynes RO, and Hodivala-Dilke KM. (2002). Enhanced pathological angiogenesis in mice lacking b3-integrin or b3- and b5-integrins. Nature Medicine, 8: 27-34. PMID: 11786903
Reynolds L, Conti FJ, Lucas M, Grose R, Robinson S, Stone M, Saunders G, Dickson C, Lacy-Hulbert A, Hynes RO, and Hodivala-Dilke KM. (2005). Accelerated re-epithelialisation in beta3-integrin-deficient mice: A novel mechanism for the regulation of TGFbeta-mediated signalling by beta3-integrin. Nature Medicine, 11: 167-174. PMID: 15654327
Reynolds AR, Hart IR, Watson A, Welti J, Silva R, Robinson SD, Da Violante G, Salih M, Jones MC, Jones DT, Saunders G, Kostourou V, Perron-Sierra F, Norman JC, Tucker GC, and Hodivala-Dilke KM. (2009). Stimulation of tumor growth and angiogenesis by low concentrations of integrin inhibitors in therapy-resistant tumors. Nature Medicine, 15(4):392-400. PMID: 19305413
Reynolds LE, Watson A, Baker M, Jones TA, D’Amico GA, 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 EMC, Tybulewicz VLJ, Hart IR, and Hodivala-Dilke KM. (2010) Tumour angiogenesis is reduced in the Tc1 mouse model of Down’s syndrome. Nature 465(7299):813-817. PMID: 20535211
For additional publications, please click here.
The Adhesion and Angiogenesis Laboratory
|T Lechertier, PhD||2008-present||CRUK fellow|
|A Alexoloupou, PhD||2010-present||CRUK fellow|
|P Wong, PhD||2010-present||MRC fellow|
|I Fernandez, PhD||2010-present||Breast Campaign fellow|
|D Lees, PhD||2012-present||CRUK fellow|
|S Batista||2012-present||AICR fellow|
|A Reynolds, PhD||2002-2007||Laboratory Head Breakthrough, London, UK|
|V Kostourou, PhD||2003-2007||Laboratory Head, Flemming Institute, Athens|
|K Scott, PhD||2003-2005||Scientific writer, MTM, Brighton, UK|
|D Jones, PhD||2005-2011||Postdoctoral fellow, Oxford University|
|L Reynolds, PhD||2000-2011||CRUK Senior Scientific Officer, BCI|
|N Bodrug||2012-2016||CRUK studentship|
|F Demircioglu||2013-2016||MRC studentship|
|F Conti||2000-2004||Postdoc, Scripps Institute, California|
|R Silva||2004-2008||Postdoc, Hospital for Sick Children, Toronto|
|G D’Amico||2004-2008||Postdoc, Karolinska Institute, Helsinki|
|M Germain||2004-2008||Research Scientist, Novartis, St Louis|
|B Tavora||2006-2010||Rockerfeller Institute, New York|
|A Watson||2006-2010||Oncology Consultant Whipps Cross Hospital, London|
|S Batista||2008-2012||CNIO, Barcelona|
|M Baker||2008-2012||BCI Digital Media and Communications Officer|
|Senior Scientific Officer|
|L Reynolds, PhD||2011-present||CRUK Senior Scientific Officer|
|S Robinson, PhD||2000-2011||Laboratory Head, University of East Anglia|
Reviewer for several Journal and grant funding bodies
- Association International Cancer Research grants committee (2012-2015)
- Barts and The London Charitable Trust Committee (2012-2015)
- NCRI committee (2012-2015)
- CR-UK Research Bursaries for clinicians / professions allied to medicine (2011-2014)
- CR-UK Clinician Scientist Interview panel (2011-2014)
- UAR Scientist for policy advisory group (2011-present)
- Chair, CR-UK Biological Resources Executive Committee (2007-2009)
- Barts and The London Projects Assessment Committee (2004-present)
- Meetings Secretary for The British Society of Cell Biology committee (2004-2010)
- CR-UK Electron Microscopy Committee (2003-2008)