Our research aims to improve the efficacy of standard of care immunotherapy, chemotherapy and radiotherapy in human solid cancers by understanding the molecular mechanisms underlying tumour stromal contributions to tumour growth and therapy efficacy. In particular we are interested in the regulatory role of cross talk of blood vessel wall cells in cancer control, using a combination of cell type-specific knockout and knockin systems in state of the art mouse models of cancer and analysis of the cellular and molecular mechanisms behind these observations. Based on our research we have patented approaches targeting blood vessels that we will aim to translate to cancer patient benefit.
Cancer Burden Is Controlled by Mural Cell-β3-Integrin Regulated Crosstalk with Tumor Cells. Cell (2020) 181(6):1346-1363.e21. PMID: 32473126.
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
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 improve the efficacy of standard of care immunotherapy, chemotherapy and radiotherapy in human solid cancers by understanding the molecular mechanisms underlying tumour stromal contributions to tumour growth and therapy efficacy. In particular we are interested in the regulatory role of cross talk of blood vessel wall cells in cancer control, using a combination of cell type-specific knockout and knockin systems in state of the art mouse models of cancer and analysis of the cellular and molecular mechanisms behind these observations. Based on our research we have patented approaches targeting blood vessels that we will aim to translate to cancer patient benefit.
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. We have exploited these ideas and have pioneered a novel concept in vascular promotion using low doses of RGD mimetics in enhancing the efficacy of cancer therapy. This has been an exciting opportunity for cutting edge research that has led to the development of patents which we hope to translate into patient benefit for the improved treatment of cancer with low side effects and extended survival.
Our team has also established the role of stromal focal adhesion kinase (FAK) not only in tumour growth and progression but also in chemoresistance. Current efforts aim to exploit these data to enhance the efficacy of not only chemotherapy but also radiotherapy and immunotherapy.
Most recently we have made fundamental discoveries in the regulation of tumour growth by blood vessel supporting cells, namely pericytes, a field we have coined pericrine signalling. These results lead us to, even more, new ways to improve therapy efficacy for patients who otherwise would not respond well to therapy.
Our overall goal is to discover novel therapeutic vascular targets to modulate stromal control in the control of cancer.
Effects of senescence on the tumour microenvironment and response to therapy Reynolds LE, Maallin S, Haston S et al. The FEBS Journal (2023) (10)
Author Correction: Pericyte FAK negatively regulates Gas6/Axl signalling to suppress tumour angiogenesis and tumour growth Lechertier T, Reynolds LE, Kim H et al. Nature Communications 14(10) 5446
Primary tumor–derived systemic nANGPTL4 inhibits metastasis Hübers C, Pari AAA, Grieshober D et al. Journal of Experimental Medicine (2023) 220(10) e20202595
ERG activity is regulated by endothelial FAK coupling with TRIM25/USP9x in vascular patterning D'Amico G, Fernandez I, Gómez-Escudero J et al. Development (2022) 149(10) dev200528
Suppression of endothelial cell FAK expression reduces pancreatic ductal adenocarcinoma metastasis after gemcitabine treatmentEC FAK regulates gemcitabine treated liver metastasis Roy-Luzarraga M, Reynolds LE, de Lux�n-Delgado B et al. Cancer Research (2022) 82(10) 1909-1925
Disruption of pancreatic stellate cell myofibroblast phenotype promotes pancreatic tumor invasion Murray ER, Menezes S, Henry JC et al. Cell Reports (2022) 38(10) 110227
Elucidating the role of the kinase activity of endothelial cell focal adhesion kinase in angiocrine signalling and tumour growth Newport E, Pedrosa AR, Lees D et al. The Journal of Pathology (2022) 256(10) 235-247
Improved Immunotherapy Efficacy by Vascular Modulation Newport EL, Pedrosa AR, Njegic A et al. Cancers 13(10) 5207
Pancreatic Cancer Chemotherapy Is Potentiated by Induction of Tertiary Lymphoid Structures in Mice Delvecchio FR, Fincham REA, Spear S et al. Cellular and Molecular Gastroenterology and Hepatology (2021) 12(10) 1543-1565
Correction to: Phosphorylation of pericyte FAK‑Y861 affects tumour cell apoptosis and tumour blood vessel regression Lees DM, Reynolds LE, Pedrosa AR et al. Angiogenesis (2021) 24(10) 483-487
For additional publications, please click hereSenior Scientific Officer
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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.
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