Judith Hellman
William L Young, M.D. Endowed Professor and Vice Chair for Research
Department of Anesthesia and Perioperative Care
University of California, San Francisco
Seminar Information
During infection and injury, interactions between microbes or endogenous host factors released in tissue injury and innate immune receptors, including Toll-like receptors (TLRs), triggers host responses designed to contain and eliminate the microbial threat or source of injury, and to initiate adaptive immune responses and the repair of injured tissue. Leukocytes have been extensively investigated in the context of sepsis, and most of the focus of research in sepsis and inflammatory critical illness focus on leukocyte responses and on circulating inflammatory mediators. In contrast, substantially less is known about the effects of microbes and products of tissue injury on cells that are not classically viewed as inflammatory cells, such as endothelial cells. Notably, the human body contains > 1 trillion endothelial cells, and endothelial cells express TLRs, produce cytokines and chemokines, and regulate leukocyte recruitment to organs. During sepsis and injury, activation and dysfunction of endothelial cells leads to vascular leak, coagulopathy, and excessive neutrophil activity in organs, and ultimately to organ injury and failure through poorly understood mechanisms. Our ongoing studies are focused on understanding the role of endothelial cell TLR-dependent signaling in sepsis and organ injury. Similarly, while much of the focus of immune modulation has been on conventional immunomodulators (e.g.: cytokine antagonists, TLR4 antagonists), the role of intrinsic homeostatic systems in regulating inflammation and sepsis have not been well characterized. In recent studies focused on understanding the immune effects of cannabinoids, we have found that several endocannabinoids as well as the phytocannabinoid, THC, have anti-inflammatory effects in vitro in endothelial cells and leukocytes activated with TLR agonists, and in vivo in endotoxemic and septic mice. The presentation will focus on non-conventional contributors to inflammatory and immune responses during injury and infection, including microvascular endothelial cell TLRs, and the endocannabinoid/endovanilloid systems.
Judith Hellman, M.D. is the William L. Young, M.D. Endowed Professor and Vice Chair for Research in the Department of Anesthesia and Perioperative Care at UCSF. She is a Critical Care Medicine physician-scientist doing basic and translational research on sepsis, injury and inflammatory critical illness. She trained clinically in Internal Medicine, Anesthesiology and Critical Care Medicine, and did a post-doctoral research fellowship in sepsis. She was on faculty at Harvard Medical School/Massachusetts General Hospital from 1997-2008, and has been on faculty at UCSF since 2008. She is the director of the UCSF Anesthesia research training program, and a faculty member of the UCSF Biomedical Sciences and Immunology programs. Her research program is focused on innate immunity in sepsis and injury, on endothelial inflammatory pathways and endothelial dysfunction, and on immune modulation by the endocannabinoid and endovanilloid systems.