Bobby J. Cherayil, M.D., M.B.,B.S.
| Title | Associate Professor of Pediatrics |
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| Institution | Massachusetts General Hospital |
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| Department | Pediatrics |
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| Address | Massachusetts General Hospital Pediatric Gastroenterology, Rm 3400 114 16th Street Charlestown MA 02129
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| Phone | 617/726-4170 |
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| Fax | 617/726-4172 |
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Overview Research in my laboratory is broadly directed at elucidating the molecular details of mammalian innate immunity, particularly in the gastrointestinal tract. We use a combination of in vitro and in vivo approaches to analyze the host factors that influence the response to infection with Salmonella typhimurium, an important agent of acute gastroenteritis in humans. In an on-going series of experiments, we are attempting to elucidate the effects of altered iron metabolism on macrophage function in salmonellosis. These studies have revealed a novel role for intracellular iron in the regulation of inflammatory cytokine biosynthesis, and have important implications for our understanding of host-pathogen interactions in conditions such as hemochromatosis.
Mentoring Available: 10/01/12, Expires: 09/03/13 My lab is interested in the interactions between iron metabolism and innate immunity. We have shown that abnormalities of systemic iron homeostasis have a significant effect on the inflammatory response to both infectious and non-infectious stimuli, and have clarified some of the underlying mechanisms. The present project is directed at exploring the effects of dietary iron on innate immune defenses in the gastrointestinal tract. The rationale for studying this issue is based on observations (both clinical and experimental) showing that oral iron supplements can exacerbate some infectious and inflammatory conditions affecting the gastrointestinal tract while an iron deficient diet can ameliorate such conditions. The mechanisms responsible for these effects are not well understood.
The project will involve the use of in vitro and in vivo (mouse) experiments to characterize the effects of iron on innate immune responses to the bacterial enteropathogen Salmonella typhimurium. In vitro, the participating student will study the effects of altering iron concentrations in the cell culture medium on the interactions between intestinal epithelial cell lines and Salmonella. Some of the parameters to be examined include bacterial invasion of the cell, cell survival, and activation of cellular inflammatory and anti-microbial responses. Similar studies will be carried out in vivo by altering the concentration of iron in the diet fed to the mice.
Further information on research in my lab can be found at www.massgeneral.org/mucosalimmunology.
The participating student should have some understanding of basic cell biology and immunology. Prior lab experience would be helpful but is not essential.
Bibliographic
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications.
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Karagiannis AK, Ziogas DC, Gras-Miralles B, Geiger BM, Nagel J, Trebicka E, Najarian R, Cherayil BJ, Kokkotou E. Increased Susceptibility of Melanin-Concentrating Hormone-Deficient Mice to Infection with Salmonella enterica Serovar Typhimurium. Infect Immun. 2013 Jan; 81(1):166-72.
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Su CW, Cao Y, Zhang M, Kaplan J, Su L, Fu Y, Walker WA, Xavier R, Cherayil BJ, Shi HN. Helminth infection impairs autophagy-mediated killing of bacterial enteropathogens by macrophages. J Immunol. 2012 Aug 1; 189(3):1459-66.
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Shanmugam NK, Ellenbogen S, Trebicka E, Wang L, Mukhopadhyay S, Lacy-Hulbert A, Gallini CA, Garrett WS, Cherayil BJ. Tumor necrosis factor a inhibits expression of the iron regulating hormone hepcidin in murine models of innate colitis. PLoS One. 2012; 7(5):e38136.
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Cherayil BJ, Ellenbogen S, Shanmugam NN. Iron and intestinal immunity. Curr Opin Gastroenterol. 2011 Oct; 27(6):523-8.
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Cherayil BJ. The role of iron in the immune response to bacterial infection. Immunol Res. 2011 May; 50(1):1-9.
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Wang L, Trebicka E, Fu Y, Waggoner L, Akira S, Fitzgerald KA, Kagan JC, Cherayil BJ. Regulation of lipopolysaccharide-induced translation of tumor necrosis factor-alpha by the toll-like receptor 4 adaptor protein TRAM. J Innate Immun. 2011; 3(5):437-46.
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Wang L, Trebicka E, Fu Y, Ellenbogen S, Hong CC, Babitt JL, Lin HY, Cherayil BJ. The bone morphogenetic protein-hepcidin axis as a therapeutic target in inflammatory bowel disease. Inflamm Bowel Dis. 2012 Jan; 18(1):112-9.
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Cherayil BJ. Iron and immunity: immunological consequences of iron deficiency and overload. Arch Immunol Ther Exp (Warsz). 2010 Dec; 58(6):407-15.
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Johnson EE, Sandgren A, Cherayil BJ, Murray M, Wessling-Resnick M. Role of ferroportin in macrophage-mediated immunity. Infect Immun. 2010 Dec; 78(12):5099-106.
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Charrière GM, Ip WE, Dejardin S, Boyer L, Sokolovska A, Cappillino MP, Cherayil BJ, Podolsky DK, Kobayashi KS, Silverman N, Lacy-Hulbert A, Stuart LM. Identification of Drosophila Yin and PEPT2 as evolutionarily conserved phagosome-associated muramyl dipeptide transporters. J Biol Chem. 2010 Jun 25; 285(26):20147-54.
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Johnson EE, Srikanth CV, Sandgren A, Harrington L, Trebicka E, Wang L, Borregaard N, Murray M, Cherayil BJ. Siderocalin inhibits the intracellular replication of Mycobacterium tuberculosis in macrophages. FEMS Immunol Med Microbiol. 2010 Feb; 58(1):138-45.
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Wang L, Harrington L, Trebicka E, Shi HN, Kagan JC, Hong CC, Lin HY, Babitt JL, Cherayil BJ. Selective modulation of TLR4-activated inflammatory responses by altered iron homeostasis in mice. J Clin Invest. 2009 Nov; 119(11):3322-8.
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Cherayil BJ. Indoleamine 2,3-dioxygenase in intestinal immunity and inflammation. Inflamm Bowel Dis. 2009 Sep; 15(9):1391-6.
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Wang L, Cherayil BJ. Ironing out the wrinkles in host defense: interactions between iron homeostasis and innate immunity. J Innate Immun. 2009; 1(5):455-64.
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Wang L, Johnson EE, Shi HN, Walker WA, Wessling-Resnick M, Cherayil BJ. Attenuated inflammatory responses in hemochromatosis reveal a role for iron in the regulation of macrophage cytokine translation. J Immunol. 2008 Aug 15; 181(4):2723-31.
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Harrington L, Srikanth CV, Antony R, Rhee SJ, Mellor AL, Shi HN, Cherayil BJ. Deficiency of indoleamine 2,3-dioxygenase enhances commensal-induced antibody responses and protects against Citrobacter rodentium-induced colitis. Infect Immun. 2008 Jul; 76(7):3045-53.
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Weng M, Huntley D, Huang IF, Foye-Jackson O, Wang L, Sarkissian A, Zhou Q, Walker WA, Cherayil BJ, Shi HN. Alternatively activated macrophages in intestinal helminth infection: effects on concurrent bacterial colitis. J Immunol. 2007 Oct 1; 179(7):4721-31.
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Harrington L, Srikanth CV, Antony R, Shi HN, Cherayil BJ. A role for natural killer cells in intestinal inflammation caused by infection with Salmonella enterica serovar Typhimurium. FEMS Immunol Med Microbiol. 2007 Nov; 51(2):372-80.
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Srikanth CV, Cherayil BJ. Intestinal innate immunity and the pathogenesis of Salmonella enteritis. Immunol Res. 2007; 37(1):61-78.
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Chlosta S, Fishman DS, Harrington L, Johnson EE, Knutson MD, Wessling-Resnick M, Cherayil BJ. The iron efflux protein ferroportin regulates the intracellular growth of Salmonella enterica. Infect Immun. 2006 May; 74(5):3065-7.
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Cariappa A, Mazo IB, Chase C, Shi HN, Liu H, Li Q, Rose H, Leung H, Cherayil BJ, Russell P, von Andrian U, Pillai S. Perisinusoidal B cells in the bone marrow participate in T-independent responses to blood-borne microbes. Immunity. 2005 Oct; 23(4):397-407.
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Rhee SJ, Walker WA, Cherayil BJ. Developmentally regulated intestinal expression of IFN-gamma and its target genes and the age-specific response to enteric Salmonella infection. J Immunol. 2005 Jul 15; 175(2):1127-36.
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Huang FC, Li Q, Cherayil BJ. A phosphatidyl-inositol-3-kinase-dependent anti-inflammatory pathway activated by Salmonella in epithelial cells. FEMS Microbiol Lett. 2005 Feb 1; 243(1):265-70.
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Li Q, Cherayil BJ. Toll-like receptor 4 mutation impairs the macrophage TNFalpha response to peptidoglycan. Biochem Biophys Res Commun. 2004 Dec 3; 325(1):91-6.
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Huang FC, Werne A, Li Q, Galyov EE, Walker WA, Cherayil BJ. Cooperative interactions between flagellin and SopE2 in the epithelial interleukin-8 response to Salmonella enterica serovar typhimurium infection. Infect Immun. 2004 Sep; 72(9):5052-62.
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Claud EC, Lu L, Anton PM, Savidge T, Walker WA, Cherayil BJ. Developmentally regulated IkappaB expression in intestinal epithelium and susceptibility to flagellin-induced inflammation. Proc Natl Acad Sci U S A. 2004 May 11; 101(19):7404-8.
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Cherayil BJ, Sengupta N. Dispatch from India. N Engl J Med. 2004 Apr 1; 350(14):1471.
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Cherayil BJ. How not to get bugged by bugs: mechanisms of cellular tolerance to microorganisms. Curr Opin Gastroenterol. 2003 Nov; 19(6):572-7.
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Li Q, Cherayil BJ. Role of Toll-like receptor 4 in macrophage activation and tolerance during Salmonella enterica serovar Typhimurium infection. Infect Immun. 2003 Sep; 71(9):4873-82.
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Cherayil BJ, Antos D. Inducible nitric oxide synthase and Salmonella infection. Microbes Infect. 2001 Jul; 3(9):771-6.
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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 effector SopE2. Infect Immun. 2000 Oct; 68(10):5567-74.
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Chaudhuri A, Orme S, Vo T, Wang W, Cherayil BJ. Phosphorylation of TRAF2 inhibits binding to the CD40 cytoplasmic domain. Biochem Biophys Res Commun. 1999 Mar 24; 256(3):620-5.
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Chaudhuri A, Orme S, Eilam S, Cherayil BJ. CD40-mediated signals inhibit the binding of TNF receptor-associated factor 2 to the CD40 cytoplasmic domain. J Immunol. 1997 Nov 1; 159(9):4244-51.
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Aoki Y, Isselbacher KJ, Cherayil BJ, Pillai S. Tyrosine phosphorylation of Blk and Fyn Src homology 2 domain-binding proteins occurs in response to antigen-receptor ligation in B cells and constitutively in pre-B cells. Proc Natl Acad Sci U S A. 1994 May 10; 91(10):4204-8.
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Cherayil BJ, MacDonald K, Waneck GL, Pillai S. Surface transport and internalization of the membrane IgM H chain in the absence of the Mb-1 and B29 proteins. J Immunol. 1993 Jul 1; 151(1):11-9.
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Rosenberg IM, Iyer R, Cherayil B, Chiodino C, Pillai S. Structure of the murine Mac-2 gene. Splice variants encode proteins lacking functional signal peptides. J Biol Chem. 1993 Jun 15; 268(17):12393-400.
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Rosenberg I, Cherayil BJ, Isselbacher KJ, Pillai S. Mac-2-binding glycoproteins. Putative ligands for a cytosolic beta-galactoside lectin. J Biol Chem. 1991 Oct 5; 266(28):18731-6.
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Cherayil BJ, Pillai S. The omega/lambda 5 surrogate immunoglobulin light chain is expressed on the surface of transitional B lymphocytes in murine bone marrow. J Exp Med. 1991 Jan 1; 173(1):111-6.
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Cherayil BJ, Chaitovitz S, Wong C, Pillai S. Molecular cloning of a human macrophage lectin specific for galactose. Proc Natl Acad Sci U S A. 1990 Sep; 87(18):7324-8.
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Cherayil BJ, Weiner SJ, Pillai S. The Mac-2 antigen is a galactose-specific lectin that binds IgE. J Exp Med. 1989 Dec 1; 170(6):1959-72.
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Cherayil BJ, Young RA. A 28-kDa protein from Mycobacterium leprae is a target of the human antibody response in lepromatous leprosy. J Immunol. 1988 Dec 15; 141(12):4370-5.
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