Contact: k.hodivala-dilke@qmul.ac.uk

Professional interests

Dr Kairbaan Hodivala-Dilke joined Barts and The London in August 2003 and is head of the Angiogenesis Laboratory (formally Cell Adhesion and Disease Laboratory).

Angiogenesis, the formation of new blood vessels, is essential for tumour growth and the spread of cancer. Anti-angiogenic therapy is therefore a logical approach to cancer treatment, but requires understanding the precise molecular mechanisms that underlie angiogenic processes. Our laboratory focuses on elucidating the molecular mechanisms involved in tumour angiogenesis with special attention to adhesion related molecules including various integrins, and downstream modulators Rac-1 and focal adhesion kinase. Our research has made major contributions to understanding the roles of adhesion molecules, especially αvβ3-integirns, in pathological 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 (Reynolds et al., Nature Medicine 2002) and has led to further discoveries of the molecular processes that regulate angiogenesis (Robinson et al., ATVB 2004; Reynolds et al., Cancer Research 2004; Reynolds et al., Nature Medicine 2005). More recently it has also led us to a better understanding of how inhibitors of αvβ3 can regulate angiogenesis (Reynolds et al., Nature Medicine, 2009). These studies have provided the foundation for subsequent funding from Cancer Research UK, Association of International Cancer Research and Breast Cancer Campaign totalling approximately £4,428,408.

Research Team:

Funding:

Breast Cancer Campaign Project grant 2009-2012 £190,00

Breast Cancer Campaign Project grant 2008-2012 £170,408

CR-UK Molecular Pathology PhD studentship 2008-2012 £120,000

CR-UK PhD studentship 2008-2012 £120,000

CR-UK Project grant 2007-2010 £250,000

CR-UK Programme grant 2005-2010 £3,250,000 "Cell Adhesion and Disease"

Breast Cancer Campaign PhD studentship 2004-2008 £160,309

Association for International Cancer Research Project grant 2005-2008 £188,432 "Understanding the role of Rac-1 in angiogenesis"

Recent Publications:

• 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. Nat Med 2009;in press.
• Ramjaun AR, Hodivala-Dilke K. The role of cell adhesion pathways in angiogenesis. Int J Biochem Cell Biol 2009;41:521-30.
• 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 re-epithelialization during wound healing in mice. J Clin Invest 2008;118:965-74.
• Scott AN, Hetheridge C, Reynolds AR, Nayak V, Hodivala-Dilke K, Mellor H. Farnesyltransferase inhibitors target multiple endothelial cell functions in angiogenesis. Angiogenesis 2008;11:337-46.
• Silva R, D'Amico G, Hodivala-Dilke KM, Reynolds LE. Integrins: the keys to unlocking angiogenesis. Arterioscler Thromb Vasc Biol 2008;28:1703-13.
• Hodivala-Dilke KM. alphavbeta3 integrin and angiogenesis: a moody integrin in a changing environment. Curr Opin Cell Biol 2008;20:514-9.
• Claxton S, Kostourou V, Jadeja S, Chambon P, Hodivala-Dilke K, Fruttiger M. Efficient, inducible Cre-recombinase activation in vascular endothelium. Genesis 2008;46:74-80.
• Boosani CS, Mannam AP, Cosgrove D, Silva R, Hodivala-Dilke KM, Keshamouni VG, Sudhakar A. Regulation of COX-2 mediated signaling by α3 type IV noncollagenous domain in tumor angiogenesis. Blood 2007;110:1168-77.
• Piqueras L, Reynolds AR, Hodivala-Dilke KM, Alfranca A, Redondo JM, Hatae T, Warner TD, Bishop-Bailey D. Activation of PPARbeta/delta induces endothelial cell proliferation and angiogenesis. Arterioscler Thromb Vasc Biol 2007;27:63-9.
• Lucas M, Stuart LM, Zhang A, Hodivala-Dilke K, Febbraio M, Silverstein R, Savill J, Lacy-Hulbert A. Requirements for apoptotic cell contact in regulation of macrophage responses. J Immunol 2006;177:4047-54.
• Reynolds LE, Hodivala-Dilke KM. Primary mouse endothelial cell culture for assays of angiogenesis. Methods Mol Med 2006;120:503-9.
• Robinson SD, Wilson S, Hodivala-Dilke KM. Generation of genetically modified embryonic stem cells for the development of knockout mouse animal model systems. Methods Mol Med 2006;120:465-77.
• Direkze NC, Jeffery R, Hodivala-Dilke K, Hunt T, Playford RJ, Elia G, Poulsom R, Wright NA, Alison MR. Bone marrow-derived stromal cells express lineage-related messenger RNA species. Cancer Res 2006;66:1265-9.
• Reynolds LE, Hodivala-Dilke K. Primary Mouse endothelial cell culture. In: Brooks, SA. Harris A, editors. Methods in Molecular Medicine Vol. 120: Breast Cancer Research Protocols. Totowa (NJ): Humana Press; 2006. p.503-10.
• Robinson S D Wilson S and Hodivala-Dilke K. Generation of genetically modified embryonic stem cells. In: Brooks, SA. Harris A, editors. Methods in Molecular Medicine Vol. 120: Breast Cancer Research Protocols. Totowa (NJ): Humana Press; 2006. p. 465-78.
• Lamagna C, Hodivala-Dilke KM, Imhof B, Aurrand-Lions M. Antibody against junctional adhesion molecule C inhibits angiogenesis and tumor growth Cancer Res 2005;65:5703-10.
• Fang J, Hodivala-Dilke KM, Johnson BD, Hynes RO, White GC 2nd, Wilcox DA. Therapeutic Expression of the Platelet-Specific Integrin αIIbβ3 in a Murine Model for Glanzmann Thrombasthenia Blood 2005;106:2671-9.
• Reynolds L, Conti FJ, Lucas M, Grose R, Robinson S, Stone M, Saunders G, Dickson C, Lacy-Hulbert A, Hynes RO, Hodivala-Dilke KM. Accelerated re-epithelialisation in β3-integrin-deficient mice: A novel mechanism for the regulation of TGFβ1-mediated signalling by β3-integrin Nat Med 2005;11:167-7.4
• Brittan M, Braun KM, Conti FJ, Reynolds AR, Poulsom R, Alison MR, Wright NA, Hodivala-Dilke KM. Bone Marrow Cells Engraft within the Epidermal Stem Cell Niche and Proliferate in vivo with no Evidence of Cell Fusion J Pathol 2005;205:1-13.
• McLean GW, Komiyama NH, Serrels B, Asano H, Reynolds L, Conti F, Hodivala-Dilke KM, Chambon P, Grant SGN, Frame MC. Conditional deletion of focal adhesion kinase from mouse skin blocks tumour initiation and malignant progression Genes Dev2004;18:2998-3003.
• Reynolds AR, Reynolds LE, Nagel T, Robinson SD, Hicklin DJ, Hodivala-Dilke KM. Enhanced VEGF receptor 2 mediated responses in β3-integrin deficient endothelial cells in vivo and in vitro. Cancer Res2004;64:8643-50.
• Direkze NC, Hodivala-Dilke KM, Jeffery R, Hunt T, Dhillon P, Craig C, Coppen M, Goldman J, Alison MR, Wright NA. Bone marrow contribution to tumour associated myofibroblasts Cancer Re 2004;64:8492-5.
• Robinson SD, Reynolds LE, Wyder L, Hicklin D, Hodivala-Dilke KM. β3-integrin regulates VEGF-A-dependent permeability. Arterioscler Thromb Vasc Biol 2004;24:2108-14.
• Mistry A, Hodivala-Dilke KM,Harbottle R, Hart S. Integrins And Angiogenesis: Unlocking The Route To Gene Therapy Curr Opin Mol Ther 2003;5:603-10.
• Hodivala-Dilke KM Reynolds A R and Reynolds L E. Integrins in angiogenesis: multitalented molecules in a balancing act Cell Tissue Res 2003;314:131-44.
• Petiot A, Conti FJA, Grose R, Revest J-M, Hodivala-Dilke KM, Dickson C. A crucial role for FgfR2-IIIb signalling in epidermal development and hair follicle patterning Development 2003;130:5493-501.
• Direkze NC, Forbes SJ, Brittan M, Hunt T, Jeffery R, Preston SL, Poulsom R, Hodivala-Dilke K, Alison MR, Wright NA. Multiple organ engraftment by bone-marrow-derived myofibroblasts and fibroblasts in bone-marrow-transplanted mice Stem Cells 2003;21:514-20.
• Alugupalli KR, Michelson AD, Joris I, Schwan TG, Hodivala-Dilke K, Hynes RO, Leong JM. Spirochete-platelet attachment and thrombocytopenia in murine relapsing fever Borreliosis Blood 2003;102:2843-50.
• Wan H, Stone MG, Simpson C, Reynolds LE, Marshall JF, Hart IR, Hodivala-Dilke KM, Eady A J. Desmosomal proteins including desmoglein 3 serve as novel negative markers for epidermal stem cells J Cell Sci 2003;116:4239-48.
• Conti FJ, Rudling RJ, Robson A, Hodivala-Dilke KM. α3β1-integrin regulates hair follicle but not interfollicular morphogenesis in adult epidermis J Cell Sci 2003;116:2737-47.
• Reynolds AR, Moghimi SM, Hodivala-Dilke K. Nanoparticle-mediated gene delivery to tumour neovasculature Trends Mol Med 2003;9:2-3.
• Hynes RO, Lively JC, McCarthy JH, Taverna D, Francis SE, Hodivala-Dilke KM, Xiao Q. The diverse roles of integrins and their ligands in angiogenesis Cold Spring Harb Symp Quant Biol 2002;67:143-53.
• Brittan M, Hunt T, Jeffery R, Poulsom R, Forbes SJ, Hodivala-Dilke K, Goldman J, Alison MR, Wright NA. Bone marrow derivation of pericryptal myofibroblasts in the mouse and human small intestine and colon Gut 2002;50:752-7.
• Schulz O, Pennington DJ, Hodivala-Dilke K, Febbraio M, Reis e Sousa C. CD36 or αvβ3 and αvβ5 integrins are not essential for MHC cross-presentation of cell-associated antigen by CD8 alpha+ murine dendritic cells J Immunol 2002;168:6057-65.
• Francis SE, Goh KL, Hodivala-Dilke K, Bader BL, Stark M, Davidson D, Hynes R.O Central roles of α5β1 integrin and fibronectin in vascular development in mouse embryos and embryoid bodies Arterioscler Thromb Vasc Biol 2002;22:927-33.
• Hodivala-Dilke K. Primary mouse keratinocyte culture Methods Mol Biol 2002;188:139-44.
• Reynolds LE, Wyder L, Lively JC, Taverna D, Robinson SD, Huang X, Sheppard D, Hynes RO, Hodivala-Dilke KM. Enhanced pathological angiogenesis in mice lacking β3-integrin or β3- and β5-integrins Nature Medicine 2002;8:27-34.
• Poulsom R, Forbes SJ, Hodivala-Dilke K, Ryan E, Wyles S, Navaratnarasah S, Jeffery R, Hunt T, Alison M, Cook T, Pusey C, Wright NA. Bone marrow contributes to renal parenchymal turnover and regeneration. J Pathol 2001;195:229-35.

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