Professor Kairbaan Hodivala-Dilke

Professor Kairbaan Hodivala-Dilke

BSc, PhD, FMedSci
Centre: Tumour Biology
Fellowships:
  • Fellow of the Academy of Medical Sciences
Professor of Angiogenesis, Deputy Institute Director
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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

2016-2019

Worldwide Cancer Research

Dual action combination therapy targeting both tumour stromal and malignant cell compartments for improved pancreatic ductal adenocarcinoma treatment,’ £249,000

2015-2018

British Heart Foundation

PhD studentship, £99,000

2015-2020

Cancer Research UK

Programme Grant, Targeting tumour blood vessels to alter angiocrine factors and enhance Chemosensitisation,’ £2,100,000

2015-2018

Barts Charity

£229,000

2012-2015

Association of International Cancer Research

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

2011-

Cancer Research UK

Large Equipment grant, £200,000

Key Publications

Dual-action combination therapy enhances angiogenesis while reducing tumor growth and spread.
Wong PP, Demircioglu F, Ghazaly E, Alrawashdeh W, Stratford MR, Scudamore CL, Cereser B, Crnogorac-Jurcevic T, McDonald S, Elia G, Hagemann T, Kocher HM, Hodivala-Dilke KM.
Cancer Cell (2015) Jan 12;27(1):123-37. PMID:
25584895

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. PMC: PMC3377344

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. Nature (2010) 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 (2009) 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

  • WeAreTheCity – Rising women stars awards, women in India (2018)
  • CRUK Science Committee (2017-)
  • Worldwide Cancer Research Board of Trustees (2017-)
  • CRUK CITA steering committee (2017-)
  • CRICK CRF CRICK Accelerator award steering committee (2016-)
  • EMBO fellowship evaluator (2016-)
  • Academy Medical Sciences Springboard fund Champion (2016-)
  • Journal Cell Science Editorial Team (2015-)

News

October 2018: Speaker at AMSlive. Watch the video below.

Keynote speeches

  • October 2016: Ludwig Institute, Distinguished Seminar, Lausanne, Switzerland

Talk highlights at conferences:

  • September 2018: International symposium on Translational Research, Dublin
  • September 2018: CRICK Symposium Cancer Research, London
  • May 2018: London Pancreas Workshop, London
  • September 2017: International symposium on Translational Research, Dublin
  • June 2017: International Conference on TME, Ascona Italy
  • June 2017: BACR meeting Tumour Microenvironment, Nottingham, UK
  • May 2017: ESM-EVBO meeting, Geneva
  • July 2016: Beatson Institute Conference, UK
  • October 2016: Ludwig Institute, Distinguished Seminar, Lausanne, Switzerland
  • September 2016: Endothelial Signalling and Vascular Repair, Frankfurt, Germany
  • September 2016: Angiogenesis Conference, Kloster Seeon, Germany
  • May 2016: TME and Metastasis meeting, Copenhagen, Denmark

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