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Research
Current Projects by Principal Investigator
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Research
Bobby Cherayil, MD 
Associate Professor of Pediatrics
Phone: 617-726-4170
Fax: 617-726-4172
Email: cherayil@helix.mgh.harvard.ed
Curriculum Vita
Fellows: C.V. Srikanth
The broad goal of my work is to understand the molecular mechanisms involved in the innate immune response to bacteria, particularly in the gastrointestinal tract. I am interested specifically in identifying the molecules involved in host-bacterial interactions, in elucidating the signaling cascades that are activated by such interactions, and in characterizing the mechanisms that regulate the host inflammatory response. The information derived from these studies will shed light on the pathogenesis of bacterial infectious diseases and chronic inflammatory states, and will pave the way for new approaches to treating these conditions.
We use Salmonella typhimurium, an important cause of acute gastroenteritis in humans, as the model organism in our experiments. As part of an NIH-funded project to understand the mechanisms of Salmonella-induced inflammation, we have found recently that during invasion of intestinal epithelial cells, signals activated by the Salmonella effector protein SopE2 cooperate with those transduced by Toll-like receptor (TLR)5 to induce expression of the pro-inflammatory chemokine, IL-8. We are currently attempting to elucidate the molecular basis for the effect of SopE2 on TLR5 signals. After crossing the intestinal epithelial barrier, Salmonella interacts with host macrophages. We have found that TLR4 plays a major role in this interaction, providing signals that are required for Salmonella-induced TNF expression, specifically at a post-transcriptional step in biosynthesis. The nature of the TLR4 signal involved in this step and the TLR4-independent signals that induce TNF transcription are the subjects of on-going experiments. Together with the laboratory of Dr. Allan Walker, we have recently identified a novel role for interferon- in the immunological maturation of anti-microbial defense mechanisms in the intestine in an in vivo murine model of Salmonella-induced colitis, an observation that could provide new insight into age-specific diseases such as necrotizing enterocolitis. Finally, I have been funded recently by the NIH to examine the role of the mammalian iron transporter ferroportin 1 in the intracellular growth of Salmonella as part of a collaborative project with Dr. Marianne Wessling-Resnick of the Harvard School of Public Health.
In addition to my laboratory research, I have been actively involved in teaching immunology to medical students. Every year for the last 6 years, I have been a tutor in HST175, a clinically-oriented, introductory course in cellular and molecular immunology offered to first year medical students, as well as some graduate students, enrolled in the Harvard-MIT Health Science and Technology program. As a tutor in this course, I lead a group of about 15 students in patient-based discussions of basic issues in immunology, a format that allows me to make effective use of both my clinical and laboratory experience.
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