Massachusetts General Hospital
Department of Medicine
Division of Infectious Diseases
65 Landsdowne St., 4th floor
Cambridge, MA 02139
The Lesser lab is interested in understanding how bacterial pathogens manipulate host cell processes to promote their own survival and replication during the course of an infection. In particular, our efforts focusing on determining how bacterial factors injected via type 3 protein delivery systems into the host cell cytosol act to disarm host innate immune responses, including the induction of pro-inflammatory cytokine production, pyroptosis and autophagy. Our studies focus on studying virulence factors from Gram-negative enteric pathogens that cause gastrointestinal diseases including Shigella, Salmonella, Yersinia and enteropathogenic E. coli. We have developed multiple innovative technologies to address these questions including an innovative bottom-up approach to study single, potentially functionally redundant effectors as well as yeast functional genomic and proteomic approaches to identify conserved eukaryotic signaling pathways targeted by the virulence proteins.
More recently, we have begun to exploit findings garnered from our mechanistic based studies to develop bacterial strains engineered to deliver proteins of therapeutic value rather than virulence proteins into host cells. Current efforts with this system are aimed at developing a viral-free protein delivery system for cellular reprogramming, i.e., the conversion of fibroblasts into induced pluripotent stem cells. In addition, we have begun to develop commensal bacteria that act suppress inflammation by blocking the production of pro-inflammatory cytokines with the goal of utilizing these bacteria to develop a new targeted treatment for inflammatory bowel disease. We are interested in expanding this system to generate therapeutics for a variety of additional human diseases.
Last Update: 1/6/2014