 |
Claudio Fiocchi, M.D.StaffThe Clifford and Jane Anthony Chair for Digestive Disease Research and Education
|
Research Programs:
Our research is focused on the pathogenesis of inflammatory bowel disease (IBD). The approach we have adopted is to investigate immune events occurring in the bowel in Crohn’s disease and ulcerative colitis patients, as well as in animal models of IBD.
Current studies include the identification of mechanisms of mucosal T-cell death and survival in gut inflammation, investigation of tolerance of mucosal T cells for autologous enteric flora and their possible loss in IBD, characterization of the interactions between mucosal T cells and endothelial and stromal cells, and the study of immune-driven angiogenesis in intestinal inflammation.
Experiments are carried out using mononuclear cells isolated from the intestinal mucosa, especially T cells and T-cell subsets, epithelial cells, microvascular endothelial cells, myofibroblasts and stromal cell-derived extracellular matrix.
Our overall goal is to uncover fundamental defects of immunoregulation that may underlie the triggering or maintenance of a chronic state of inflammation in the bowel.
Investigators:
- Sean Kessler, Ph.D.
- Franziska Mohr, M.D.
- Ilche Nonevski, M.D.
- M. (Homa) Phillips, M.S.
- Melanie Rhee, Ph.D.
- Heitor Souza, M.D.,Ph.D.
- Gail West, B.S.
- Christina Williams, M.D.
Grant Support:
- NIH/NIDDK, 5R37 DK30399 (C. Fiocchi, PI)
Title: Mucosal Lymphokines in Inflammatory Bowel Disease
This study is aimed at the investigation of the signal transduction pathways involved in activation, growth and regulation of mucosal T-cells derived from normal and inflammatory bowel disease involved intestine. - NIH/NIDDK, 5R01 DK50984 (C. Fiocchi, PI)
Title: Cell Interactions in the Inflamed Intestinal Mucosa
This study is aimed at the investigation of the interaction between immune and non-immune cells in the pathogenesis of inflammatory bowel disease. Specifically, mesenchymal and endothelial cells from the intestinal mucosa will be assessed for their capacity of modulating the function of mucosal T lymphocytes. - NIH/NIDDK, RO1 DK69854 (C. Fiocchi, PI)
Title: The role of angiogenesis in IBD pathogenesis
This proposal focuses on the potential role of new vessel formation in the intestinal mucosa on the initiation and maintenance of chronic intestinal inflammation.
Key References:
Sturm A, Itoh J, Jacobberger JW, Fiocchi C. p53 acts as a negative regulator of intestinal immunity by delaying the cell cycle kinetics of mucosal T-cells. J Clin Invest 109:1481-1492, 2002. PDF
Danese S, de la Motte C, Sturm A, West GA, Strong SA, Katz JA, Fiocchi C. Platelets trigger a CD40-dependent inflammatory response in the microvasculature of inflammatory bowel disease patients. Gastroenterology 124:1249-1264, 2003.
Lawrance IC, Wu F, Willis J, West GA, Fiocchi C, Chakravarti S. A murine model of chronic inflammation-induced intestinal fibrosis. Gastroenterology 125:1750-1761, 2003. PDF
Vogel JD, West GA. Danese S, de la Motte C, Phillips MH, Strong SA, Willis J, Fiocchi C. CD40-mediated immune-nonimmune cell interactions trigger mucosal fibroblast chemokine production causing T-cell transmigration. Gastroenterology 126:63-80, 2004. PDF
Sturm A, Leite AZ, Danese S, Krivacic KA, West GA, Mohr S, Jacobberger JW, Fiocchi C. Divergent cell cycle kinetics underlie the pathogenesis of chronic inflammatory diseases. Gut 53:1624-1631, 2004. PDF
Fiocchi C. Closing fistulas in Crohn's disease - Should the accent be on maintenance or safety? N Engl J Med 350:934-936, 2004. PDF
Ina K, Kusugami K, Kawano Y, Nishiwaki T, Wen Z, Musso A, West GA, Ohta M, Goto H, Fiocchi C. Intestinal fibroblast-derived IL-10 increases survival of mucosal T-cells by inhibiting growth factor deprivation- and Fas-mediated apoptosis. J Immunol 175:2000-2009, 2005. PDF
Fiocchi C. One commensal bacterial molecule - All we need for health? N Engl J Med 353:2078-2080, 2005. PDF
Danese S, Sans, M, de la Motte C, Graziani C, West G, Phillips MH, Pola R, Rivera-Reyes BM, Willis J, Gasbarrini A, Fiocchi C. Angiogenesis as a novel component of inflammatory bowel disease pathogenesis. Gastroenterology 130:2060-2073, 2006. PDF
Danese S, Fiocchi C. The etiopathogenesis of inflammatory bowel diseases. World J Gastroenterology 14:4807-4812, 2006. PDF
Fiocchi C. Probiotics in inflammatory bowel disease: yet another mechanism of action? Gastroenterology 131:2009-2012, 2006. PDF
Danese S, Dejana E, Fiocchi C. Immune regulation by microvascular endothelial cells: directing innate and adaptive immunity, coagulation, and inflammation. J Immunol 2007;178:6017-22. PDF
Danese S, et al. Angiogenesis blockade as a new therapeutic approach to experimental colitis. Gut 2007;56:855-62. PDF
Danese S, et al. Critical role of the CD40 CD40-ligand pathway in regulating mucosal inflammation-driven angiogenesis in inflammatory bowel disease. Gut 2007;56:1248-56. PDF
Sans M, Danese S, De La Motte C, de Souza HSP, Rivera-Reyes BM, West GA, Phillips M, Katz JA, Fiocchi C. Enhanced recruitment of CX3CR1+ T cells by mucosal endothelial cell-derived fractalkine in inflammatory bowel disease. Gastroenterology 132:139-153, 2007. PDF
Rieder F, Cheng L, Harnett KM, Chak A, Cooper GS, Isenberg G, Ray M, Katz JA, Catanzaro A, O'Shea R, Post AB, Wong R, Sivak MV, McCormick T, Phillips M, West GA, Willis JE, Biancani P, Fiocchi C. Gastroesophageal reflux disease-associated esophagitis induces endogenous cytokine production leading to motor abnormalities. Gastroenterology 132:154-165, 2007. PDF
Kugathasan S, Fiocchi C. Progress in basic inflammatory bowel disease research. Semin Pediatr Surg. 16(3):146-53. Review, 2007. PDF
Kugathasan S, Saubermann LJ, Smith L, Kou D, Itoh J, Binion DG, Levine AD, Blumberg RS, Fiocchi C. Mucosal T-cell immunoregulation varies in early and late inflammatory bowel disease. Gut. 56(12):1696-705, 2007. PDF
Scaldaferri F, Fiocchi C. Inflammatory bowel disease: progress and current concepts of etiopathogenesis. J Dig Dis. 8(4):171-8. Review, 2007.
Sturm A, de Souza HS, Fiocchi C. Mucosal T cell proliferation and apoptosis in inflammatory bowel disease. Curr Drug Targets. 9(5):381-7. Review, 2008.
Awards and Honors:
- 1991 Premier Physician Award, Crohn's and Colitis Foundation of America.
- 1997 Certificate of Teaching Excellence, Internal Medicine
- 1997 Residents, University Hospitals of Cleveland.
- 1997 Intestinal Disease Research Unit Lecture Award. University of Calgary, Calgary, Canada.
- 1999 Award of the "Agostinho Bettarello Medal" for contributions to gastroenterology research and teaching. University of S. Paulo School of Medicine, S. Paulo, Brazil.
- 1999 Honorary Member, Brazilian Association for Ulcerative Colitis and Crohn's Disease (ABCD). S. Paulo, Brazil.
- 1999 MERIT Award (R-37), NIDDK, NIH.
- 2000 Adjunct Professor, Division of Gastroenterology, University of Padua School of Medicine, Padua, Italy.
- 2000 Dean's Visiting Professor, West China University School of Medicine, Chengdu, Sichuan, P.R. China.
- 2000 Million Dollar Professor, Case Western Reserve University School of Medicine.
- 2001 Roy and Robert Kroc Distinguished Professor in Medicine and Immunology. University of California, Davis, School of Medicine.
- 2005 Honorary Member, Portuguese Society of Gastroenterology.
- 2005 Dr. Luois Zetzel Visiting Professor, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA