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Laboratory Staff
Curriculum Vita
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Curriculum Vita
  Bobby Cherayil, MD
Associate Professor of Pediatrics
GENERAL INFORMATION
Date Prepared: November 19, 2005
Name: Bobby Joseph Cherayil
Office Address:
Laboratory of Mucosal Immunology,
Pediatric Gastroenterology Unit,
Massachusetts General Hospital,
Building 114, Room 3400,
16th Street,
Charlestown, MA 02129
E-mail: cherayil@helix.mgh.harvard.edu
Phone: 617-726-4170
Fax: 617-726-4172
Place of Birth: North Parur, India
Citizenship: United States of America
Education:
1981 MBBS Christian Medical College, Vellore, India - General Medicine
1984 MD Christian Medical College, Vellore, India - Pediatrics
Postdoctoral Training:
Internships, Residencies and Clinical Fellowships:
1980-1981 Rotating intern, Christian Medical College Hospital, Vellore, India
1981-1984 Resident in pediatrics, Christian Medical College Hospital,Vellore, India
1992-1993 Resident in pediatrics, Columbia-Presbyterian MedicalCenter, New York
1995- 2000 Clinical fellow in pediatric gastroenterology, Massachusetts General Hospital, Boston
Research Fellowships:
1985-1986 Research fellow, Dept. of Molecular Biophysics and Biochemistry, Yale University, New Haven
1986-1988 Research fellow, The Whitehead Institute, Cambridge
1988-1992 Research fellow, Massachusetts General Hospital, Boston
Licensure and Certification:
1991 Educational Council for Foreign Medical Graduates
1994 American Board of Pediatrics. Recertified 2001
2000 Full medical license - Board of Registration in Medicine, Massachusetts
2004 License renewal
Academic Appointments:
1985-1986 Research fellow, Dept. of Molecular Biophysics and Biochemistry, Yale University, New Haven
1986-1988 Research fellow, The Whitehead Institute, Cambridge
1988-1992 Research fellow, Massachusetts General Hospital, Boston
1992-1993 Postdoctoral residency fellow, Pediatrics Dept., College of Physicians & Surgeons, Columbia University, New York
1993-1994 Assistant Professor, Pediatrics Dept., College of Physicians & Surgeons, Columbia University, New York
1994-2005 Assistant Professor, Pediatrics Dept., Harvard Medical School, Boston
2005 - Associate Professor, Pediatrics Dept., Harvard Medical School, Boston
Hospital Appointments:
1994- Associate immunologist, Massachusetts General Hospital, Boston
2002-2006 Assistant Pediatrician, Massachusetts General Hospital, Boston
Major Committee Assignments:
Medical School
2004- Member, Harvard Medical School Committee on Immunology
Massachusetts General Hospital
2001- Member, MGH Immunology Committee
2002 Member, review committee, MGH Fund for Medical Discovery
2003- Member, MGH sub-committee on review of research proposals
2003- Chair, departmental committee on pediatric clinical fellowship research
National
2004 Member, NIH Special Salmonella Study Section
International
2003-2004 Coordinator, international organizing committee, Third Winter Symposium, Christian Medical College, Vellore, India
Professional Societies:
2003- American Association of Immunologists
2004- American Society for Microbiology
Editorial Boards:
2000-2001 Senior editor, Cell, Molecular Cell
Reviews editor, Immunity
2003-2005 Ad hoc reviewer, Journal of Immunology
2003- Ad hoc reviwer, Journal of Leukocyte Biology
2004- Ad hoc reviewer, Infection and Immunity
2005- Associate editor, Journal of Immunology
Awards and Honors:
1972 OBA Gold Medal, St. Joseph's High School, Bangalore, India.
1973 National Science Talent Scholarship, New Delhi, India.
1974 George Chacko Memorial Award for Best Incoming Student, Christian Medical College, Vellore, India.
1977 Capt. Jaisingh Jadhav Prize in Pediatrics, Christian Medical College, Vellore, India.
1980 Maria Viakulam David Gold Medal for Best Outgoing Student, Christian Medical College, Vellore, India.
1980 The Raja of Panagal Gold Medal for Best Medical Graduate, University of
Madras, Madras, India.
1990 The Charles A. King Fellowship of the Medical Foundation, Boston.
1995 AGA/Sandoz Pharmaceuticals Research Scholar Award.
1996 First Award, Crohn's and Colitis Foundation of America.
RESEARCH AND TEACHING CONTRIBUTIONS
A. Narrative Report of Research:
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 TNFa 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 TNFa 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-g 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.
B. Research Funding Information:
1990-92 The Medical Foundation. Fellow. Studies on the macrophage IgE binding protein Mac-2
1991-92 CSIBD, MGH. Pilot Investigator. Studies on the macrophage IgE binding protein Mac-2
1995-96 American Cancer Society. Principal Investigator. The role of the CD40 binding protein in B cell activation
1995-97 American Gastroenterology Assoc. Principal Investigator. Signal transduction by CD40 in B lymphocytes
1996-98 Crohn's and Colitis Foundation of America. Principal Investigator. CD40 signal transduction and its effects on B lymphocytes and intestinal epithelial cells
1998 CSIBD, MGH. Principal Investigator. Serum-induced morpho genesis in Candida albicans
2000-05 NIH-NIDDK. Investigator. Barrier function of the GI tract in health and disease
2001-06 NIH-NIAID. Principal Investigator. Induction of macrophage iNOS by Salmonella
2004-05 Wyeth Pharmaceuticals. Principal Investigator. Effect of dairy based ingredients on Salmonella induced inflammatory responses and intracellular signaling pathways in intestinal epithelial cells
2005-07 NIH-NIAID (R21 AI065619). Principal Investigator. Mammalian metal transporters and Salmonella infection
C. Current Research Activities (Bench Research):
1. Project: Activation of innate immune responses by Salmonella.
Role: Principal investigator
2. Project: Barrier functions of the GI tract.
Role: Co-investigator
3. Project: Developmental regulation of innate immune responses to bacteria in the gut.
Role: Co-investigator
4. Project: Mammalian metal transporters and Salmonella infection.
Role: Principal investigator
D. Report of Teaching:
1. Local contributions:
a. Harvard Medical School courses:
1997 Patient-Doctor II, tutor, two medical students, 7 hours contact time, 3 hours preparation time.
1998 Immunology 200, lecturer, 20 graduate students, 1.5 hours contact time, 2 hours preparation time.
1997 -2005 HST175, Cellular and Molecular Immunology, tutor, 15 medical and graduate students per year, 16 hours contact time, 8 hours preparation time.
2003-2005 HST175, Cellular and Molecular Immunology, lecturer, 60 medical and graduate students, 2 hours contact time, 4 hours preparation time.
b. Advisory and supervisory responsibilities:
1994 - Post-doctoral training program in Pediatric GI and Nutrition, preceptor
2001- HMS Fellowship in Pediatric GI and Nutrition, preceptor
c. Advisees and trainees:
Undergraduate students
1996 Erin O'Brien, DePauw University
1998 Eugene Chiu, DePauw University
2000 Jacob Bosley, DePauw University
2002 David Scott, DePauw University
2003 Adam Werne, DePauw University
Medical students
1995 Alice Wong, State University of New York, Stonybrook
2001 David Antos, University of Munich, Germany
Post-doctoral fellows
1996 - 1999 Amit Chaudhuri, PhD, currently Senior Scientist, Genentech Corp.
2001 - 2004 Erika Claud, MD, currently Asst. Prof. of Pediatrics, Univ. of Chicago
2002 - 2004 Fu-Chen Huang, MD, currently Pediatric Gastroenterologist, Chang Gung Memorial Hospital, Taiwan
2003 - 2005 Sue Rhee, MD, currently Asst. Prof. of Pediatrics, UCSF
2004 - 2005 Sabine Chlosta, MD (MD thesis advisee, Univ. of Berlin, Germany)
2005 - C.V. Srikanth, PhD
2. Regional, national and international contributions:
Invited presentations:
1992 Lecture: Surface transport and endocytosis of the mm heavy chain in the absence of mb-1 and B29. FASEB Meeting, Anaheim, CA.
1992 Lecture: Assembly and transport of membrane immunoglobulin. Indian Institute of Science, Bangalore, India.
1995 Lecture: CD40 stimulation inhibits apoptosis and promotes cell cycle progression in the human B cell line BJAB. 8th International Congress of Mucosal Immunology, San Diego, CA.
1995 Lecture: The role of TRAF proteins in CD40 signaling. Tata Institute of Fundamental Research, Bangalore, India.
1997 Lecture: TRAF2 and signaling by members of the TNF receptor family. 7th Annual Symposium of the Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, MA.
1998 Lecture: TRAF2 and signaling through CD40. Dept. of Biochemistry, Indian Institute of Science, Bangalore, India.
2002 Lecture: Innate immune responses to intestinal bacteria. National Centre for Biological Sciences, Bangalore, India.
2003 Lecture: Innate immune responses to intestinal bacteria. Renal Unit, MGH Seminar series, Boston, MA.
2003 Lecture: Toll-like receptors and the innate immune response to Salmonella typhimurium. MGH Immunology Committee, Boston, MA.
2003 Lecture: Toll-like receptors and the innate immune response to Salmonella typhimurium. Beth-Israel Deaconess Hospital, Boston, MA.
2003 Lecture: Toll-like receptors and the innate immune response to Salmonella typhimurium. Harvard Medical School fellowship in pediatric gastroenterology and nutrition, Childrens Hospital, Boston, MA.
2004 Lecture: Innate immune responses to Salmonella typhimurium. Dept. of Geographic Medicine, New England Medical Center, Boston, MA.
2004 Grand rounds: Host responses to Salmonella and what they tell us about innate immunity. Dept. of Pediatrics, MGH, Boston, MA.
2004 Lecture: Interactions between TLR5- and SopE2-activated signals during Salmonella infection of epithelial cells. American Association of Immunologists, Washington, DC.
2004 Lecture: Close encounters and dangerous liaisons: interactions between Salmonella and the mammalian host. Third Annual Winter Symposium, Christian Medical College, Vellore, India.
2005 Lecture: Age-dependent changes in intestinal gene expression modulate the immune response to enteric Salmonella infection. Fifteenth Annual Symposium of the Center for the Study of Inflammatory Bowel Diseases, MGH, Boston, MA.
PART III: BIBLIOGRAPHY
Original reports:
1. Krupp, G., Cherayil, B.J., Frendeway, D., Nishikawa, S. and Soll, D. Two RNA species co-purify with RNase P from the fission yeast S. pombe. The EMBO J. 1986; 5: 1697-1703.
2. Cherayil, B.J. Personal view. Brit. Med. J. 1986; 293: 46.
3. Cherayil, B.J., Sridharan, G., Thangavelu, C.P., Steinhoff, M., Koshi, G. and Pereira, S.M. Is a clinical diagnosis of streptococcal pharyngitis possible in the ropics? J. Trop. Ped. 1987; 33: 157.
4. Cherayil, B.J., Krupp, G., Char, S. and Soll, D. The RNA components of S. pombe RNase P are essential for cell viability. Gene 1987; 60: 157-161.
5. Cherayil, B.J. and Young, R. A 28 kD protein from M. leprae is a target of the human antibody response in lepromatous leprosy. J. Immunol. 1988; 141: 4370- 4375.
6. Cherayil, B.J., Weiner, S. and Pillai, S. The Mac-2 antigen is a galactose-specific lectin which binds IgE. J. Exp. Med. 1989; 170: 1959-1972.
7. Cherayil, B.J., Chaitovitz, S., Wong, C. and Pillai, S.. Molecular cloning of a human macrophage lectin specific for galactose. Proc. Natl. Acad. Sci. USA 1990; 87: 7324-7328.
8. Cherayil, B.J. and Pillai, S. The w/l 5 surrogate immunoglobulin light chain is expressed on the surface of transitional B lymphocytes in murine bone marrow. J. Exp. Med. 1991; 173: 111-116.
9. Rosenberg, I., Cherayil, B.J., Isselbacher, K. and Pillai, S. Mac-2 binding glycoproteins: putative ligands for a cytosolic b-galactoside lectin. J. Biol. Chem. 1991; 266: 18731-18736.
10. Rosenberg, I., Iyer, R., Cherayil, B.J., Chiodino, C. and Pillai, S. Structure of the Mac-2 gene: splice variants encode proteins lacking functional signal peptides. J. Biol. Chem. 1993; 268: 12393-12400.
11. Cherayil, B.J., MacDonald, K., Waneck, G. and Pillai, S. Surface transport and internalization of the membrane IgM heavy chain in the absence of the mb-1 and B29 proteins. J. Immunol. 1993; 151: 11-19.
12. Aoki, Y., Isselbacher, K.J., Cherayil, B.J. and Pillai, S. Tyrosine phosphorylation of Blk and Fyn SH2 domain binding proteins occurs in response to antigen receptor ligation in B cells and constitutively in pre-B cells. Proc. Natl. Acad. Sci. USA 1994; 91: 4204-4208.
13. Chaudhuri, A., Orme, S., Eilam, S. and Cherayil, B.J. CD40-mediated signals inhibit the binding of TRAF2 to the CD40 cytoplasmic domain. J. Immunol. 997; 159: 4244-4251.
14. Cherayil BJ, McCormick BA, Bosley J. Salmonella enterica serovar Typhimurium-dependent regulation of inducible nitric oxide synthase expression in macrophages by invasins SipB, SipC and SipD and the effector SopE2. Infect Immun 2000; 68:5567-74.
15. Li Q, Cherayil BJ. Role of Toll-like receptor 4 in macrophage activation and tolerance during Salmonella enterica serovar Typhimurium infection. Infect Immun 2003; 71:4873-82.
16. Claud EC, Lu L, Anton P, Savidge T, Walker WA, Cherayil BJ. Developmentally-regulated IkB expression in intestinal epithelium and susceptibility to flagellin-induced inflammation. Proc Natl Acad Sci USA 2004; 101:7404-8.
17. Li Q, Cherayil BJ. Toll-like receptor 4 mutation impairs the macrophage TNFa response to peptidoglycan. Biochem. Biophys. Res. Comm. 2004; 325: 91-96.
18. Huang FC, Werne A, Li Q, Galyov EE, Walker WA, Cherayil BJ. Cooperative interactions between flagellin and SopE2 in the epithelial IL-8 response to Salmonella. Infect Immun 2004; 72: 5052-5062.
19. Huang FC, Li Q, and Cherayil BJ. A phosphatidyl-inositol-3-kinase-dependent anti-inflammatory pathway activated by Salmonella in epithelial cells. FEMS Microbiol Lett. 2005; 243: 265-270.
20. Rhee SJ, Walker WA, and Cherayil BJ. Developmentally-regulated intestinal expression of IFNg and its target genes and the age-specific response to enteric Salmonella infection. J Immunol 2005; 175: 1127-1136.
21. Cariappa A, Mazo IB, Chase C, Shi HN, Liu H, Li Q, Rose H, Leung H, Cherayil BJ, Russell P, von Andrian U and Pillai S. Perisinusoidal B cells in the bone marrow mediate T-independent IgM responses to blood-borne microbes. Immunity 2005; 23: 397-407.
Invited reviews and chapters:
1. Cherayil BJ, Antos D. Inducible nitric oxide synthase and Salmonella infection. Microbes Infect 2001; 3:771-6.
2. Cherayil BJ, Walker WA. Ontogeny of the host response to enteric microbial infection. In: Hecht G, editor. Microbial Pathogens and the Intestinal Epithelial Cell. Washington, DC: ASM Press; 2003. p. 333-49.
3. Cherayil BJ. How not to get bugged by bugs: mechanisms of cellular tolerance to microorganisms. Curr Opin Gastroenterol 2003;19: 572-7.
4. Cherayil BJ. NF-kB-dependent responses activated by bacterial-epithelial interactions. In: McCormick B, editor. Bacterial-Epithelial Cell Cross-Talk: Molecular Mechanisms in Pathogenesis. Cambridge University Press, New York, NY. 2005. In press.
Clinical communications:
1. Cherayil BJ. Personal view. Brit Med J 1986; 293: 46.
2. Cherayil BJ, Sengupta N. Dispatch from India (correspondence). N Engl J Med 2004; 350:1471.
Abstracts:
1. Cherayil BJ, Eilam S, Orme, S. TRAF2 and TRAF3 bind to overlapping but distinguishable sites on the CD40 cytoplasmic domain. AAAAI/AAI/CIS Joint Meeting, San Francisco, CA, February 21-26, 1997.
2. Chaudhuri A, Orme S, Cherayil BJ. Binding of TRAF2 to the cytoplasmic domain of CD40 is regulated by phosphorylation. Meeting on Tyrosine Phosphorylation and Cell Signaling. The Salk Institute for Biological Sciences, San Diego, CA, August 15-19, 1998.
3. Claud, EC, Cherayil BJ, Walker WA. Developmental regulation of the enterocyte inflammatory response to bacteria. Annual meeting of the Society for Pediatric Research, Seattle, WA, May 3-6, 2003.
4. Cherayil BJ, Huang FC, Werne A, Li Q, Galyov EE, Walker WA. Interactions between TLR5- and SopE2-activated signals during Salmonella infection of epithelial cells. Annual meeting of the American Association of Immunologists, Washington, DC, April 17-21, 2004.
5. Claud EC, Anton P, Lu L, Savidge T, Cherayil BJ, Walker WA. Developmental regulation of IkB expression in the intestinal epithelium. Annual meeting of the Pediatric Academic Society, San Francisco, CA, May 1-4, 2004.
6. Rhee SJ, Walker WA, and Cherayil BJ. Developmental changes in expression of interferon g-regulated genes in the intestine contribute to age-specific differences in the response to enteric Salmonella infection. Digestive Disease Week, Chicago, IL, May 14-19, 2005.
7. Chlosta S, Fishman DS, Harrington L, Wessling-Resnick M , and Cherayil BJ. The iron efflux protein ferroportin 1 regulates intracellular growth of Salmonella. Keystone Symposium on Innate Immunity, Banff, Alberta, Feb. 15-19, 2006.
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