Dennis Kasper, M.D.
Talk Title: Microbiome Impacts Cancer Immunotherapy
Dennis L. Kasper, M.D., conducts research in microbiology, immunology, infectious diseases and carbohydrate chemistry. Dr. Kasper is the William Ellery Channing Professor of Medicine and Professor of Immunology at Harvard Medical School.
Dr. Kasper has studied the carbohydrates of group B Streptococcus, the foremost cause of serious neonatal bacterial infections and Bacteroides fragilis, an important intestinal commensal. His studies innovatively integrate structural carbohydrate chemistry, microbiology, immunology, biochemistry, and genetics. He elucidated the structure of all nine capsular polysaccharides and important surface proteins of group B Streptococcus and their role in immunity and derived a highly immunogenic glycoconjugate vaccine, now in clinical trials. He has developed a new understanding of the immune mechanism’s leading to glycoconjugate vaccine responses.
A major focus of his current work is on the microbiome, often using Bacteroides fragilis as a model organism, Kasper delineated the microbiota’s centrality in immune system development, maturation, and regulation, initiating a new and dynamic research field. He defined the phylogenetic diversity, immune mechanisms, and immunomodulatory therapeutic potential of bacteria and bacterial molecules from the microbiome in autoimmune and infectious diseases.
Studying B. fragilis, he discovered capsular polysaccharides on the organism's surface. Remarkably, single strains produce multiple phase-varying polysaccharides; at least two have a zwitterionic charge motif. Overturning immunologic paradigms, he discovered how one zwitterionic polysaccharide, PSA, is processed via the endosomal MIIC pathway in antigen-presenting cells, depolymerized by NO-dependent deamination, and presented to CD4+ T-cells by MHCII. His lab then found an essential role for PSA in shaping mammalian immune development by stimulating normal splenic CD4+ T cell numbers, TH1/TH2 balance and thereby directing splenic organogenesis. PSA has potent immunomodulatory and anti-inflammatory activity stimulating CD4+ T-cell production of IL-10, which protects against inflammatory bowel disease and experimental autoimmune encephalitis (EAE). His lab tailored click chemistry to visualize live gut anaerobic commensals and to track specific microbial immunomodulatory molecules into the immune system. His group defined the microbiota’s role in early-life establishment of iNKT cell numbers in colon and lung, determining underlying mechanisms and discovering bacterial glycosphingolipid Bf717, which confers lifelong resistance to experimental ulcerative colitis through iNKT cell immunoregulation. PSA and Bf717 are the only identified immunomodulatory molecules from the microbiome. Kasper’s studies of bacterial–immune system interactions have extraordinary physiologic and therapeutic implications.
Dr. Kasper has directed 2 major NIH sponsored centers for research in emerging infectious diseases. He was the Chairman of the NIH sponsored, National Science Advisory Board on Biosecurity and served as Executive Dean for Academic Programs at Harvard Medical School. Dr. Kasper is a member of the National Academy of Medicine and the National Academy of Sciences.
He is the author of more than 450 publications encompassing an array of topics in infectious disease, chemistry, microbiology, and immunology.