Beth Israel Deaconess Medical Center 330 Brookline Ave; DA-501
Boston, MA 02215
Advanced Degree And Training Info:
Year
Institution
Area or Rank
1965
Univ of Rochester
Medicine
1971
Mass General Hospital
Fellow in GI
1975
Brigham and Women
Asst Prof
1980
Boston University Med Center
Assoc Prof Chief of GI Di
1985
Boston Univ
Prof of Medicine
1995
BIDMC Harvard Med School
Chief of GI Prof of Medic
Research Team Listing
No team members listed
Areas of Interest:
Infectious Diseases, Inflammation
Patient Oriented / Translational
Major Research Theme:
We work on the structure and function of Clostridium difficile toxins. These protein exotoxins are among the class of enterotoxins, and they are the main virulence factor for this pathogen , the cause of pseudomembranous colitis. We are trying to elucidate the signal transduction pathways in mammalian enterocytes exposed to toxins A and B of C. difficile. The toxin receptors are surface proteins that help internalize the toxins. Toxin action involves a profound effect on mitocondrial function and activation of protein kinase c.We have also identified a membrane protein that serves as a receptor for C difficie toxins and facilitates cell binding /internalization.
Warny et al. p38 MAP kinase activation by C. difficile toxin A J. Clin Invest 105:1147-56, 2000.
Chen M, Pothoulakis C, Lamont JT. PKC signalling Z0-1 translocation and increased paracellular flux of T84 colonocytes exposed to Clostridium difficile toxin A. J. Biol Chem, 277: 4247-4254, 2002
Na X, Zhao D, Koon HW, Kim H, Husmark J, Moyer MP, Pothoulakis C, and Lamont JT. Clostridium difficile Toxin B activates the EGF receptor and the ERK/MAP kinase pathway in human colonocytes. Gastroenterology, 2005; 128:1002-1011
Kim H, Kokkotou E, Na X, Rhee SH, Moyer MP, Pothoulakis C, Lamont JT. Closstridium difficile toxin A-induced colonocyte apoptosis involves p53-dependent-p21 (WAF1/CIP1) induction via p38 MARK. Gastroenterology 2005; In Press
Kim H, Rhee SH, Kokkotou E, Na X, Savidge T, Moyer MP, Pothoulakis C, and Lamont JT. Clostridium difficile Toxin A regulates inducible cyclooxygenase-2 and prostaglandin E2 synthesis in colonocytes via reactive oxygen species and activation of p38 MAPK. J. Biol. Chem., 280: 21237-21245, 2005
External Recognition:
NIH Merit Award 1996-2006 , Assoc Editor NEJM , Past chair, NIH- NIDDK Subcommittee C( Training Grants Review committee). Chair, NIH-NIDDK Boundary Team in Digestive Diseases, Past Senior Assoc Editor, Gastroenterology, Member FDA Review Panel on GI Drugs.
Major Collaborative Activities:
We interact with laboratories in BIDMC ( Surgery, Endocrinology, Cardiology ) Childrens Hospital, Mass General Hospital, Boston University School of Medicine, University of Chicago and Stanford University School of Medicine
