Professor Murray Clarke

Murray CH Clarke

PHSA-Engage Mutual Health Professor of Cardiovascular Diseases.

Email: mchc2@cam.ac.uk

Twitter: @MurrayClarkeLab

Mastodon/other social media:

Biography 

I am a group leader with extensive experience in cardiovascular, cell death and immunology research. For the last 15 years I have been successfully running a research group whose interests lie in understanding the downstream consequences of cell death, how this influences innate and adaptive immunity, and how this affects cardiovascular disease. My group has a strong interest in the apical inflammatory cytokine IL-1, and we have identified novel molecular mechanisms that control its activation and signalling, and how aberration of these drive immune dysfunction in vivo. We also have a strong interest in cellular senescence and how IL-1α drives senescent cell-associated inflammation, which is pivotal in multiple diseases.

Research Approach:

Discovery science into mechanisms driving inflammation in the vessel wall and myocardium. Cell culture, innate immunity, adaptive immunity, immunoassays, IL-1, inflammasomes, cell senescence; animal models, disease modelling, generation of novel GM mice.

Current projects:

• How can we target senescent cell-driven vascular inflammation whilst sparing host defence?
• Does clonal haematopoiesis drive atherosclerosis via IL-1β, or does atherosclerosis create a permissive environment to drive clonal haematopoiesis?
• Investigating the role of macrophage polarisation on interleukin-1 expression and release.
• Atypical activation and release of IL-1β by human VSMCs.
• The role of IL-1R2 in controlling IL-1-driven inflammation and adaptive immunity in atherosclerosis and other diseases.

Selected Publications:

1. Pyrillou K, Humphry M, Kitt L, Rodgers A, Nus M, Bennett MR, Smith GC, Lyons P, Mallat Z, Clarke MCH. Loss of T follicular regulatory cell-derived IL-1R2 augments germinal centre reactions via increased IL-1. JCI Insight. 2024; 9(5):e174005.
2. Burzynski LC, Morales-Maldonado MA,  Rodgers A, Kitt LA, Humphry M, Figg N, Bennett MR, Clarke MCH. Thrombin activated Interleukin-1α drives atherogenesis, but also promotes VSMC proliferation and collagen production. Cardiovascular Research. 2023; Jun 13; doi.org/10.1093/cvr/cvad091.
3. Burzynski LC, Humphry M, Pyrillou K, Wiggins KA, Chan JNE, Figg N, Kitt LL, Summers C, Tatham KC, Martin PB, Bennett MR, Clarke MCH. The coagulation and immune system are directly linked through the activation of interleukin-1α by thrombin. Immunity. 2019; 50, 1033–1042.
4. Wiggins KA, Parry AJ, Cassidy L, Webster SJ, Humphry M, Goodall JC, Narita M, Clarke MCH. IL-1α cleavage by inflammatory caspases of the non-canonical inflammasome controls the senescence-associated secretory phenotype. Aging Cell. 2019; 18(3):e12946.
5. Gardner SE, Humphry M, Bennett MR, Clarke MCH. Senescent vascular smooth muscle cells drive inflammation through an interleukin-1α-dependent senescence-associated secretory phenotype. ATVB. 2015; 35(9):1963-74.