J. Thomas Lamont, M.D. received his medical degree in 1965 from the University of Rochester, and was intern, resident and chief resident in Medicine at UCLA. Following GI Fellowship at Massachusetts Hospital, he joined the faculty of Harvard Medical School in 1974. From 1980 to 1995 he was Chief of GI at Boston University School of Medicine, and since 1996 has been GI Division Chief at Beth Israel Deaconess Medical Center and Rabb Professor of Medicine at Harvard Medical School.
Dr. Lamont's research interests are in the area of intestinal infections, particularly the pathophysiology and clinical features of Clostridum difficile infections. Recent studies from his laboratory have focused on the nature of the cell membrane receptor fro toxin A of C difficile. This toxin ( MW 308 kd ) binds to surface receptors on all nucleated cells. No cell type has yet been discovered which is insensitive to this toxin , or to the closely related toxin B. Recent evidence suggests that the cell surface receptor on human enterocytes is a member of the heat shock family of proteins. GP 96 is located on the luminal-facing membrane of colonocytes. Pull down studies with labeled toxin indicate that this protein binds avidly to toxin A but not toxin B. Cells with diminished expression of GP96 are less sensitive to the biologic effects of the toxin.
It has been known for some time that C. difficile toxin A impairs tight junction function of colonocytes by glucosylation of Rho family proteins causing actin filament disaggregation and cell rounding. We recently investigated the effect of toxin A on focal contact formation by assessing its action on focal adhesion kinase (FAK) and the adapter protein paxillin. Exposure of NCM460 human colonocytes to toxin A for 1 hour resulted in complete dephosphorylation of FAK and paxillin, while protein tyrosine phosphatase activity was reduced. Blockage of toxin A-associated glucosyltransferase activity by co-incubation with UDP 2'3'dialdehyde did not reduce toxin A-induced FAK and paxillin dephosphorylation. GST-pull down and in vitro kinase activity experiments demonstrated toxin A binding directly to the catalytic domain of Src with suppression of its kinase activity. Direct binding of toxin A to Src, independent of any effect on protein tyrosine phosphatase or Rho glucosylation, inhibits Src kinase activity followed by FAK/paxillin inactivation. These mechanisms may contribute to toxin A-associated cellular detachment that occurs in human colonic epithelium exposed to toxin A.
Dr Lamont recently closed his research laboratory after 35 years of continuous NIH support including two separate research projects on intestinal mucin and C difficile toxins, as well as an NIH T32 training grant. However, he continues to be active as a mentor for young scientists and junior faculty members in the GI Division. Dr Lamont is serving as a resource for manuscript and grant preparation , and for career planning for medical students, post-doctoral PhD fellows, residents and GI fellows. He currently serves as Associate Editor for GI and Liver Diseases at the New England Journal of Medicine, and as Editor-in-Chief for Gastroenterology for "UpToDate in Medicine".