Professor Kairbaan Hodivala-Dilke

Professor Kairbaan Hodivala-Dilke

BSc, PhD, FMedSci
Centre: Tumour Biology
Professor of Angiogenesis, Deputy Institute Director
This email address is being protected from spambots. You need JavaScript enabled to view it.

QMUL Directory


Cancers are composed of both tumour and stromal compartments.

We are interested in understanding the molecular basis of how the stroma contributes to tumour growth and spread, particularly tumour angiogenesis in various solid tumours including lung cancers, pancreatic cancer and melanoma.

 

Research Details

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.

This work led to international collaborations and further discoveries of how this, and other integrins such as α3β1 and α6β1, can also regulate angiogenesis. These studies also guided us to a better understanding of how low doses of αvβ3 inhibitors can upregulate angiogenesis. 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.

Additionally, we have exploited a mouse model of Down’s 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.

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. 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

Tavora B, Reynolds LE, Batista S, Demircioglu F, Fernandez I, Lechertier T, Lees DM, Wong P-P, Alexopoulou A, Elia G, Clear A, Ledoux A, Hunter J, Perkins N, Gribben JG, Hodivala-Dilke KM. Endothelial-FAK is required for the maintenance of chemoresistance. Nature (2014) Jul 27. doi: 10.1038/nature13541. PMC: PMC3377344

Kostourou V, Lechertier T, Ramjaun AR, Jones DT, Baker M, Birdsey G, Reynolds LE, Tavora B, Robinson SD, Parsons M, Randi AM, Hart IR, Hodivala-Dilke KM. (2013). FAK-heterozygous mice display enhanced tumour angiogenesis. Nature Communications. (2013); 4:2020. doi: 10.1038/ncomms3020 PMID: 23799510

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

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, 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

 


Further Publications

For additional publications, please click here.


Cancers are composed of both tumour and stromal compartments.

We are interested in understanding the molecular basis of how the stroma contributes to tumour growth and spread, particularly tumour angiogenesis in various solid tumours including lung cancers, pancreatic cancer and melanoma.

 

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

  • January 2015: Cancer Cell: vascular promotion therapy study published
  • October 2014: Nature Communications paper on the effects of bone marrow FAK
  • July 2014: Publication in Nature on the role of endothelial FAK in chemoresistance
  • May 2014: Spoke at the London Pancreas Workshop
  • 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
This site uses cookies in order to function properly. By continuing to browse, you agree that we can save them on your device. Privacy Policy.