Dennis L. Kasper
Harvard University
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Primary Section: 44, Microbial Biology Secondary Section: 43, Immunology and Inflammation Membership Type:
Member
(elected 2018)
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Biosketch
Dennis Kasper's research integrates microbiology, immunology, structural carbohydrate and lipid chemistry, and genetics. Kasper is from Chicago and earned an MD from University of Illinois School of Medicine in 1967. After residencies in internal medicine at New York Hospital and Boston’s Peter Bent Brigham Hospital, he began his research career at Walter Reed Army Institute of Research. He trained in infectious diseases on the Harvard Service at Boston City Hospital. Kasper's many honors include the Squibb Award from the Infectious Diseases Society of America, an NIH Career Development Award, an NIH Merit Award, and election to the American Society for Clinical Investigation, the American Association of Physicians, and the American Academy of Microbiology. Kasper served as the first Chair of the National Science Advisory Board on Biosecurity, Chair of the NIAID's Board of Scientific Counselors, and President of the International Society for Infectious Diseases. At Harvard Medical School, he served as Executive Dean for Academic Programs and Director of the Channing Laboratory. Since 1990, he has been an Editor of Harrison’s Principles of Internal Medicine. Kasper has authored over 450 articles in his field. He is a member of the National Academy of Medicine (2001). In 2018, Kasper was elected to the National Academy of Sciences.
Research Interests
Kasper studies the microbiota's role in immune system development, maturation, and regulation. His lab defines the phylogenetic diversity, immune mechanisms, and chemical structures of bacteria and bacterial molecules from the microbiota and examines their therapeutic potential in immunomodulation and pathogenesis of autoimmune/infectious diseases. His group discovered and structurally elucidated polysaccharide A (PSA) from Bacteroides fragilis, an important member of the gut microbiota. PSA stimulates both innate and adaptive immunity and suffices for restoring normal immune balance in germ-free mice. Kasper investigated how carbohydrates are handled by the innate and adaptive immune systems, establishing that complex carbohydrates are oxidatively processed and depolymerized in the endosome. After depolymerization, PSA can bind to MHCII because of its zwitterionic charge motif and interact with the abT cell receptor. PSA stimulates TLR2, activates plasmacytoid dendritic cells, and is presented to Tregs via MHCII. IL-10 produced by these Tregs prevents experimental inflammatory bowel disease and autoimmune encephalomyelitis. Kasper’s lab tailors click chemistry to visualize live gut anaerobic commensals and to track specific microbial immunomodulatory molecules into the immune system. Kasper studies the microbiota's role in early-life establishment of immune cells in various tissues. His work identifies bacterial molecules critical to bacterial–immune system interactions (e.g., sphingolipids, which confer resistance to experimental ulcerative colitis through immunoregulation of iNKT cell homeostasis) and elucidates underlying mechanisms.
