Research

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.

Other Activities

• Deputy Director, Barts Cancer Institute (2012- )
• City of London CRUK Major Centre Exec Board (April 2022-)
• City of London CRUK Major Centre Multidisciplinary Theme co-lead (2019-)
• CRUK Barts Centre Tumour Microenvironment Theme 5 lead (2019- )
• Barts Cancer Insitute Centre of Tumour Microenvironment lead (2019- )
• CRUK RadNet Executive Board, Theme 2 co-lead (2019- )

Major Funding

• 2021-2026- CRUK Programme Grant, Exploiting the effects of low mural cell beta-3-integrin in the control of cancer progression, therapy resistance and metastasis, £2.2M
• 2022-2025- Barts Charity, Novel combination strategies for the improved treatment of lung cancer, (£445,621)
• 2021-2024- Medical Research Council, Investigating the role of vascular endothelial-cell senescence driving resistance to DNA-damaging therapies and metastasis formation in lung cancer, £736,661
• 2020-2023- Pancreatic Cancer Research Fund, Reducing pancreatic cancer metastasis by targeting the endothelial cell niche (PCRF 2019), £200,000
• 2019-2022- CRUK City of London Radiation Research Unit RadNet Co-lead, £14M
• 2019-2022- Worldwide Cancer Research, Improving the efficacy of immunotherapy in advanced lung cancer’, £208,000

Recent Publications

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

Team

Senior Scientific Officer

• Louise Reynolds, PhD

Postdoctoral Researchers

• Rita Pedrosa, PhD
• Jesus Escudero, PhD
• Laura Wisniewski, PhD
• Alexandra Njegic, PhD
• Juan Marti, PhD

PhD Students

• Rebecca Drake                   

Technicians

• Julie Holdsworth
• Bruce Williams

Biography