Clara Abraham

Assistant Professor
Section of Digestive Diseases

Research Interests

Regulation of the intestinal immune system; T cell trafficking and activation

Research Interests

Homeostasis of the intestinal immune system. The development of inflammatory bowel disease appears to be related to the uncontrolled activation of immune cells within the specialized immune system of the intestine. We are addressing mechanisms in intestinal immune homeostasis through studies in murine models of disease and through the use of primary cells from patients with Crohn’s disease and ulcerative colitis. In particular, we focus on understanding the immunological consequences of genetic polymorphisms implicated in either increasing or decreasing the likelihood of developing human inflammatory bowel disease.

The role of lymphocyte function-associated molecule-1 (LFA-1) in T cell activation and T cell trafficking. The leukocyte-specific adhesion molecule and integrin, LFA-1, plays a critical role in T cell activation and T cell migration to both lymphoid and non-lymphoid tissues. LFA-1 deficiency in humans and mice is characterized by recurrent infections and early death. We are interested in understanding the molecular mechanisms wherein LFA-1 participates in these processes. We further seek to understand the role of LFA-1, as well as other integrins, in the trafficking of cells specifically to the intestinal immune system.

Clinical Interests

Gastrointestinal Diseases

Selected Publications

• Li J, Moran T, Swanson E, Julian C, Harris J, Bonen DK, Hedl M, Nicolae DL, Abraham C, Cho JH. Regulation of IL-8 and IL-1ß expression with Crohn’s disease associated NOD2/CARD15 mutations. Hum Mol Genet, 13:1715-1725, 2004.
• Kandula S and Abraham C. LFA-1 on CD4+ T cells is required for optimal antigen-dependent activation in vivo. J Immunol, 173:4443-4451, 2004.
• Wang J, Anders RA, Wang Y, Turner JR, Abraham C, Pfeffer K, and Fu YX. The critical role of LIGHT in promoting intestinal inflammation and Crohn’s Disease. J Immunol, 174:8173-8182, 2005.
• Marski M, Kandula S, Turner JR, Abraham C. CD18 is required for optimal development and function of CD4+ CD25+ T regulatory cells. J Immunol, 175: 7889-7897, 2005.
• Abraham C and Cho JH. Clinical Implications of Basic Research: Inducing intestinal growth. N Engl J of Med, 353:2297-2299, 2005.
• Wang F, Schwarz BT, Graham, WV, Wang Y, Su L, Clayburgh DR, Abraham C, Turner JR. IFN-?-induced TNFR2 expression is required for TNF-dependent intestinal epithelial barrier dysfunction. Gastroenterology. 131:1153-1163, 2006.
• Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, Abraham C, Regueiro M, Griffiths A, Dassopoulos T, Bitton A, Yang H, Targan S, Datta LW, Kistner EO, Schumm LP, Lee A, Gregersen PK, Barmada MM, Rotter JI, Nicolae KL, Cho JH. A Genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science, 314:1461-1463, 2006.
• Abraham C and Cho JH. Functional consequences of NOD2 mutations. Inflamm Bowel Dis 12:641-650, 2006.
• Marski M, Ye AL, Abraham C. CD18 is required for intestinal T cell responses at multiple immune checkpoints. J Immunol, 178:2104-2112, 2007.
• Cho JH and Abraham C. Inflammatory Bowel Disease genetics: Nod2. Annu Rev Med. 58:401-416. 2007.
• Molinero L, Zhou P, Wang Y, Harlin H, Cosmano J, Yokota Y, Kee B, Abraham C, Alegre ML. Epidermal Langerhans cells play a major role in skin allograft rejection in mice with NF-κB-impaired T cells. Am J Transplant, epub Nov 16, 2007.
• Abraham C and Cho JH. Bugging of the Intestinal Mucosa. N Engl J Med, 357:708-710, 2007.
• Hedl M, Li J, Cho JH, Abraham C. Chronic stimulation of NOD2 mediates tolerance to bacterial products. Proc Natl Acad of Sci USA, epub Nov 21, 2007.

Contact

Campus Address
Department of Internal Medicine
Section of Digestive Diseases
333 Cedar Street (LMP 1080)
New Haven, CT 06520

E-mail
clara.abraham@yale.edu

Office Phone
203-785-5610