Hodivala-Dilke

Professor Kairbaan Hodivala-Dilke

BSc, PhD
Centre: Tumour Biology
Job Title: Professor of Angiogenesis, Deputy Institute Director
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Research Interests


Professor Kairbaan Hodivala-Dilke's main research themes are in: Adhesion and Integrins, Tumour Angiogenesis, Cancer Cell Biology, Metastasis and Invasion, Pancreatic Cancer 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 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.

 

Profile

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.

Funding

2013

Medical Research Council

£28,020

2012

Cancer Research UK

Cancer Metastasis Symposium
£4,000

2012

Cancer Research UK

Large equipment Award
£200,000

2012-2015

Association for International Cancer Research

"Development of a novel pre-angiogenic approach for cancer therapy"
£260,803

2010-2013

Medical Research Council

Project Grant: "Elucidating the role of JAM-B in breast cancer and angiogenesis"
£417,336

2010-2015

Cancer Research UK

Programme Grant: "Modelling the stromal regulation of tumour angiogenesis"
£1,954,035

2010-2013

Breast Cancer Campaign

Project Grant: "Elucidating the role of vascular Rac1 in breast cancer metastasis"
£221,840

2009

Cancer Research UK

Conference Grant
£1,000

2008-2011

Cancer Research UK

Project Grant: "The role of endothelial Y397 - FAK"
£141,739

2009-2012

Breast Cancer Campaign

Project Grant: "Ribosomal Protein L29 (RPL29)"
£200,577

2008-2012

Breast Cancer Campaign

Project Grant: "Role of FAK in breast cancer angiogenesis"
£172,308

2008-2012

Cancer Research UK

PhD studentship
£120,000

2008-2011

Cancer Research UK

Molecular Pathology of Cancer Training Programme PhD studentship
£120,000

 

Key Publications

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. Tumour angiogenesis is reduced in the Tc1 mouse model of Down’s syndrome. (2010) Nature 465(7299):813-817. PMID: 20535211

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. Regulation of lymphatic-blood vessel separation by endothelial Rac1. (2009) Development, 136(23):4043-4053. PMID: 19906871

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. Stimulation of tumor growth and angiogenesis by low concentrations of integrin inhibitors in therapy-resistant tumors. (2009) Nature Medicine, 15(4):392-400. PMID: 19305413

Reynolds LE, Conti FJ, Silva R, Robinson SD, Iyer V, Rudling R, Cross B, Nye E, Hart IR, Dipersio CM, Hodivala-Dilke KM. alpha3beta1 integrin-controlled Smad7 regulates reepithelialization during wound healing in mice. (2008) J Clin Invest, 118(3):965-74. PMID: 18246199

 


Further Publications

For additional publications, please click here.

Research Group

The Adhesion and Angiogenesis Laboratory

 

Postdoctoral fellows
Current
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
Past
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
PhD students
Current
N Bodrug 2012-2016 CRUK studentship
F Demircioglu 2013-2016 MRC studentship
Past
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
Current
L Reynolds, PhD 2011-present CRUK Senior Scientific Officer
Past
S Robinson, PhD 2000-2011 Laboratory Head, University of East Anglia

External Activities

Reviewer for several Journal and grant funding bodies

Committees

  • 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)


News

  • September 2013: Presented year 13 STARS students with completion certificates
  • September 2013: Welcoming speaker for BBSRC symposium
  • July 2013: Invited speaker at BACR, Bristol
  • July 2013: Work presented by lab members at the Beatson International Cancer Conference
  • June 2013: Publication in Nature Communications on FAK in cancer and angiogenesis
  • June 2013: Invited speaker at the Cold Spring Harbour conference
  • May 2013: Spoke to 600 Cancer Research UK fundraisers about "Life in the Lab"
  • May 2013: Publication in PLOS ONE on Claudin-14 in angiogenesis
  • April 2013: Spoke to A level students at the British Library during the Crick Education Meeting
  • November 2012: Speaker and "Meet the Professor" participant at NCRI
  • May 2011: Speaker at Fibronectin Gordon Research Conference
  • April 2011: Speaker at AACR