Our research aims to examine the molecular mechanisms underlying tumour stromal contributions to tumour growth and therapy efficacy. In particular we are interested in angiogenesis, the formation of new blood vessels and the cancer associated fibroblasts roles, using a combination of cell type-specific knockout and knockin systems in mouse models of cancer and analysis of the cellular and molecular mechanisms behind these observations.
Dual-action combination therapy enhances angiogenesis while reducing tumor growth and spread. Cancer Cell (2015) 27(1):123-37. PMID: 25584895
Endothelial-FAK is required for the maintenance of chemoresistance. Nature (2014) 2(12): 516–528. PMID: 21154724
Tumour angiogenesis is reduced in the Tc1 mouse model of Down’s syndrome. Nature (2010) 465(7299):813-817. PMID: 20535211
Stimulation of tumor growth and angiogenesis by low concentrations of integrin inhibitors in therapy-resistant tumors. Nature Medicine (2009) 15(4):392-400. PMID: 19305413
Our research aims to examine the molecular mechanisms underlying tumour stromal contributions to tumour growth and therapy efficacy. In particular we are interested in angiogenesis, the formation of new blood vessels and the cancer associated fibroblasts roles, using a combination of cell type-specific knockout and knockin systems in mouse modelsof cancer and analysis of the cellular and molecular mechanisms behind these observations.
Our research has historically 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.
These studies also guided us to a better understanding of how low doses of αvβ3 inhibitors can upregulate 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.
We have also established the role of stromal focal adhesion kinase (FAK) not only in tumour growth and progression but also in chemoresistance.
Lastly we have pioneered a novel concept in vascular promotion using low doses of RGD mimetics in enhancing the efficacy of cancer therapy.
Our overall goal is to discover novel therapeutic vascular targets to modulate stromal control in the control of cancer.
Pericyte FAK negatively regulates Gas6/Axl signalling to suppress tumour angiogenesis and tumour growth Lechertier T, Reynolds LE, Kim H et al. Nature Communications (2020) 11(7)
Association of Low Tumor Endothelial Cell pY397-Focal Adhesion Kinase Expression With Survival in Patients With Neoadjuvant-Treated Locally Advanced Breast Cancer Roy-Luzarraga M, Abdel-Fatah T, Reynolds LE et al. JAMA network open (2020) 3(7) e2019304
Tumor Cell-Derived Angiopoietin-2 Promotes Metastasis in Melanoma. Abdul Pari AA, Singhal M, Hübers C et al. Cancer Res (2020) 80(2) 2586-2598
Cancer Burden Is Controlled by Mural Cell-β3-Integrin Regulated Crosstalk with Tumor Cells Wong PP, Muñoz-Félix JM, Hijazi M et al. Cell (2020) 181(7) 1346-1363.e21
Cancer associated fibroblast FAK regulates malignant cell metabolism. Demircioglu F, Wang J, Candido J et al. Nature Communications (2020) 11(1) 1290-1290
C-type natriuretic peptide co-ordinates cardiac structure and function Moyes AJ, Chu SM, Aubdool AA et al. European Heart Journal (2020) 41(7) 1006-1020
Macrophages induce malignant traits in mammary epithelium via IKKε/TBK1 kinases and the serine biosynthesis pathway Wilcz-Villega E, Carter E, Ironside A et al. EMBO Molecular Medicine (2020) 12(7)
“Splitting the matrix”: intussusceptive angiogenesis meets MT1-MMP D'Amico G, Muñoz-Félix JM, Pedrosa AR et al. EMBO Molecular Medicine (2020) 12(7)
Novel Pure αvβ3 Integrin Antagonists That Do Not Induce Receptor Extension, Prime the Receptor, or Enhance Angiogenesis at Low Concentrations Li J, Fukase Y, Shang Y et al. ACS Pharmacology and Translational Science (2019) 2(7) 387-401
Repurposing an anti-cancer agent for the treatment of hypertrophic heart disease Dukinfield M, Maniati E, Reynolds LE et al. Journal of Pathology (2019) 249(7) 523-535For additional publications, please click here
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 fuelled 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.