Mark is a Professor of Immunology based in the Lydia Becker Institute of Immunology and Inflammation, the Division of Immunology, Immunity to Infection & Respiratory Medicine, and the Wellcome Trust Centre for Cell-Matrix Research.

Mark received a first class honours degree in Biochemistry and Genetics from Lancaster University in 2000, and completed a PhD in protein biochemistry at the University of Manchester in 2004, studying the structure and function of integrin adhesion receptors. He then went to the University of California, San Francisco, as an American Lung Association Fellow, where he worked on the role of integrins and TGF-beta in immune regulation. Mark returned to Manchester as a Royal Commission Fellow in late 2006, before taking up a position as an RCUK Fellow in October 2007. Mark became a Lecturer in 2012, a Senior Lecturer in 2015 and Professor in 2018, and is currently Head of Division for the Division of Immunology, Immunity to Infection, and Respiratory Medicine.

Regulation of immune responses at barrier surfaces

The immune system has evolved to protect the body from harmful pathogens. To function properly, the immune system must be tightly regulated so that it is switched on/off only at appropriate times and in appropriate locations in the body. When this regulation is compromised, disease situations can arise- for example, overwhelming infection if the immune system is not activated appropriately in response to pathogens, or autoimmune disease (e.g. inflammatory bowel disease, diabetes, arthritis) if the immune system is not prevented from attacking self-tissues. Therefore, understanding the factors and pathways that are important in regulation of the immune system will be important in understanding pathologies caused by abberant immune responses.

Our work focuses on how immune responses are regulated at mucosal barrier sites- specifically the lung and the intestine. These are esepcially tricky places for the immune system, as they must ignore the plethora of harmless substances that we breath in or ingest, and also the commensal microbes that reside in the lung and gut, but be poised to deal with any pathogens that enter through.

A molecule that we extensively study is the cytokine TGF-beta. TGF-beta is secreted from cells in an inactive form that needs to be activated to exert effects on TGF-beta receptor-expressing cells. We have identified the integrin receptor, alphavbeta8, is an important activator of TGF-beta in the immune system, and our current research focuses on understanding the mechanisms and important biological outcomes of integrin-mediated TGF-beta activation in the immune system. Specifically, how is integrin-mediated TGF-beta activation controlled? How does this process affect other immune cell types in order to mediate its function? What other biological outcomes are controlled by integrin-mediated TGF-beta activation? Answering these questions will provide important insights into how TGF-beta functions, and the pathways by which TGF-beta tightly regulates immune responses.

The immune system must be rapidly activated to eliminate infection, but be tightly regulated to prevent self-harmful immune responses. When this regulation breaks down, severe health problems can occur, such as uncontrolled infection or autoimmune disorders (where the immune system attacks the body’s own tissues and organs). My lab aims to identify important cells and molecules that control immune responses in health and disease, especially in mucosal tissues such as the lung and gut.

We study broad mechanisms that regulate the immune system at these sites, but have a long-standing interest in how the cytokine TGF-beta regulates mucosal immunity. Many cells make TGF-beta, but always as an inactive complex, and we have previously identified molecules of the integrin family that are key regulators of mucosal immunity via activation of TGF-beta. Our current work aims to identify processes that regulate TGF-beta activity and function, and how this is altered in infection and disease.