Dennis L. Kasper, M.D.
Professor of Immunology, Harvard Medical School
For more than four decades, Dr. Dennis Kasper has conducted research in microbiology, immunology, infectious diseases, and public health while discharging a broad range of administrative and educational responsibilities. His studies innovatively integrate microbiology, immunology, structural carbohydrate and lipid chemistry, biochemistry, and genetics.Dr. Kasper discovered and developed vaccines against group B Streptococcus (GBS), the foremost cause of serious neonatal bacterial infections. His laboratory elucidated the structure of all nine capsular polysaccharides and important surface proteins of this major neonatal pathogen. His group discovered that antibodies to the bacterial capsule are deficient in babies with GBS disease. Ultimately, Dr. Kasper's work led to a highly immunogenic glycoconjugate vaccine, which is now in clinical trials; in a novel approach, pregnant women are immunized and then transplacentally transfer antibodies to protect the baby. Dr. Kasper defined much of what is known about the pathogenesis of GBS infection and developed an understanding of the polysaccharide conformational epitopes required for induction of protective antibodies. His group explored the physical/chemical parameters required in a conjugate vaccine for optimal immunogenicity and redefined the immunologic mechanisms by which conjugate vaccines stimulate the immune system.
Dr. Kasper's work on Bacteroides fragilis, an important intestinal commensal, has served as a paradigm for understanding the interrelationship of the gut microbiota and the immune system. Kasper discovered capsular polysaccharides on the organism's surface that are essential for virulence. Remarkably, Dr. Kasper’s laboratory found that single strains of B. fragilis produce multiple phase-varying polysaccharides, at least two of which 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 documented an essential role for PSA in shaping mammalian immune development by stimulating normal splenic CD4+ T cell numbers, establishing TH1/TH2 balance, and thereby directing splenic organogenesis. Kasper showed that 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 (the animal model for multiple sclerosis).
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. His lab developed a novel methodology for moving beyond correlative microbiome-wide analysis to discover key disease-modulating microbes and molecules: they 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 B. fragilisglycosphingolipid Bf717, which confers lifelong resistance to experimental ulcerative colitis through iNKT cell immunoregulation. PSA and Bf717 are the only immunomodulatory molecules from the microbiome identified so far.
Dr. Kasper’s investigations have opened new fields of research on the role of microbial molecules in shaping immune system development and have enabled probing of the microbiome for new therapeutics. Kasper’s studies of bacterial–immune system interactions have extraordinary physiologic and therapeutic implications.
Dr. Kasper has been awarded many honors, including the Squibb Award from the Infectious Diseases Society of America, an NIH Career Development Award, an NIH Merit Award, and the Professor John McArthur Award. He has been elected to membership in the American Society for Clinical Investigation, the American Association of Physicians, and the American Academy of Microbiology. He is also a member of the National Academy of Medicine, and in 2018 was elected to membership in the National Academy of Sciences. Dr. Kasper directed the New England Regional Center of Excellence for Biodefense and Emerging Infectious Diseases and is currently the Principal Investigator of a Center of Excellence in Translational Research at Harvard Medical School. Dr. Kasper was the first Chair of the National Science Advisory Board on Biosecurity. He served as Executive Dean for Academic Programs at Harvard Medical School, as a member and Chair of the NIAID's Board of Scientific Counselors, and as President of the International Society for Infectious Diseases. From 1995 to 2012, Dr. Kasper was the Director of the Channing Laboratory, a research facility with a high international profile, where he played a powerful role in shaping cutting-edge research programs in microbiology and immunology. He has mentored over 70 graduate students and postdoctoral fellows, many of whom are national and international academic leaders. Since 1990, Dr. Kasper has served as the Infectious Disease Editor for Harrison’s Principles of Internal Medicine (HPIM). He was Editor-in-Chief of both the 16th and 19th editions of HPIM. He is the author of more than 450 scientific and medical articles in his field.
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