Stephen Tomlinson, Ph.D.

NEED PHOTO

Professor
Department: Microbiology & Immunology
Programs: Cell Injury, Inflammation, End Organ Disease

 

Research Interests:

Dr. Tomlinson’s liver-related research projects involve the investigation of the complement activation event and complement effector mechanisms involved in the balance between post-ischemic sterile inflammation and injury and tissue repair/regeneration. His studies closely align with the DDRCC thematic areas of cell injury, inflammation, fibrosis, and disease.

A component of Dr. Tomlinson’s research involves the development and characterization of a novel targeted complement inhibitory strategy that dissects the dual role of complement in these processes, and protects against injury without impairing tissue repair. Available data indicate similar complement activation and effector mechanisms are involved in post-ischemic injury and repair/regeneration processes of various organs and tissues, including the liver which is his focus. Dr. Tomlinson’s overall working hypothesis is that complement is activated by natural self-reactive IgM that binds to various neoepitopes exposed after ischemia, and that the complement terminal membrane attack complex (MAC) plays a key role in IRI, whereas more proximal activation products (C3a and C5a) are important for repair and regeneration. He has isolated a panel of novel self-reactive IgM mAbs, and will use these mAbs to investigate immunological changes (neoepitope exposure) and the complement activation event that occurs after either ischemia and reperfusion (IR) or after partial hepatectomy (PHx). A focus will be on understanding how the terminal complement pathway is involved in tissue injury and protection, since we have shown a key role for the MAC in IRI of multiple organs/tissues and, importantly, that C6 deficiency or MAC blockade protects against hepatic IRI while enhancing regeneration after PHx. Concurrent with these studies will be the development of a therapeutic approach to reduce inflammation while promoting repair/regeneration. The research approach will be based on a novel targeting strategy to locally deliver a complement inhibitor to post-ischemic neoepitopes.

Publications:

PubMed Collection