William Ellery Channing Professor of Medicine
Professor of Microbiology and Molecular Genetics
Harvard Medical School

Senior Physician
Brigham and Women's Hospital

Click HERE to go to Dr. Kasper's Harvard web page.

dennis.kasper@channing.harvard.edu

An infection occurs when a potentially virulent organism comes into contact with a susceptible host. Dr. Kasper’s group is studying the molecular basis for bacterial pathogenesis from both the host’s and the organism’s perspective. Studies are aimed at the molecular, chemical, and genetic basis for the interactions of the immune system with bacteria and with important bacterial components, particularly capsular polysaccharides and surface or secreted proteins. The overall goal is to develop an understanding of host-organism interactions that will lead to new preventive or therapeutic interventions.

We are studying immune responses to important bacterial molecules, focusing on the elucidation of immune system responses to bacterial colonization and infection. The primany emphasis of this work has been on bacterial carbohydrates, particularly capsular polysaccharides and lipopolysaccharides. One major goal is to understand how commensal bacteria interact with the host and stimulate immune development. We have identified and described symbiotic carbohydrate molecules from the intestinal microflora that play a key role in stimulating organogenesis and in balancing the host's CD4+ T cells so that the immune system responds appropriately to challenge during infection or allergic reactions. These molecules are polysaccharides whose documented stimulation of T cell development runs counter to the earlier immunologic paradigm that carbohydrates are T cell-independent antigens. In fact, these molecules are processed and presented by the MHCII pathway. We are examining the mechanisms by which these polysaccharides stimulate immune development. We are also workking on how the commensal flora signal the immune system and the impact of this signaling on immune homeostasis.

Another area of our work deals the Francisella tularensis, which is considered a potential agent of bioterrorism. We have taken a reverse-vaccinology approach to developing a vaccine against this important pathogen. We have cloned and expressed the entire proteome of the organism and have begun to screen the expressed proteins for their ability to induce cellular immunity. Through this ongoing immunologic screening, we will identify proteins that elicit protective immune responses, as assessed by cytokine production, and we will select vaccine candidates for further studies.