Clara Abraham MD
Associate Professor of Medicine (Digestive Diseases)
Regulation of the intestinal immune system; T cell trafficking and activation; Genetics and immunobiology of inflammatory bowel disease
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 mouse models of disease and through the use of primary cells from healthy individuals and patients with Crohn’s disease and ulcerative colitis. In particular, we focus on understanding the immunological consequences of genetic polymorphisms (e.g. Nod2, IL23/Th17 pathway) 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.
- Zheng S and Abraham C. NFkB1 inhibits NOD2-induced cytokine secretion through ATF3-dependent mechanisms. Mol Cell Biol (in press).
- Hedl M and Abraham C. Nod2-induced autocrine IL-1 alters signaling by ERK and p38 to differentially regulate secretion of inflammatory cytokines. Gastroenterology. 143:1530-1543, 2012.
- Huber S, Gagliani N, Zenewicz LA, Huber FJ, Hedl M, Zhang W, O’Connor W, Murphy AJ, Valenzuela DM, Yancopoulos GD, Booth CJ, Cho JH, Ouyang W, Abraham C, Flavell RA. The IL-22—IL-22BP axis is regulated by the inflammasome and modulates tumorigenesis in the intestine. Nature. 491:259-263, 2012.
- Hedl M and Abraham C. IRF5 Risk Polymorphisms Contribute to Inter-Individual Variance in Pattern-Recognition Receptor-Mediated Cytokine Secretion in Human Monocyte-Derived Cells. J Immunol, 188:5348-5356, 2012.
- Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, Lee JC, Schumm LP, Sharma Y, Anderson CA, Essers J, Mitjovic M, Ning K, Cleynen I, Theatre E, Spain SL, Raychaudhuri S, Goyette P, Wei Z, Abraham C, Achkar JP, Ahmad T, Amininejad L, Ananthakrishnan A, Andersen V, Andrews JM, Baidoo L, Balschun T, Bampton PA, Bitton A, Boucher G, Brand S, Buning C, Cohain A, Cichon S, D’Amato M, De Jong D, Devaney KL, Dubinsky M, Edwards C, Ellinghous D, Ferguson LR, Franchimont D, Fransen K, Gearry R, Gieger C, Glas J, Haritunians T, Hart A, Hawkey C, Hedl M, Hu X, Karlsen TH, Kupinskas L, Kugathasan S, Latiano A, Laukens D, Lawrance IC, Lees CW, Louis E, Mahy G, Mansfield J, Morgan AR, Mowat C, Newman W, Palmieri O, Ponsioen CY, Potocnik U, Prescott NJ, Regueiro M, Rotter JI, Russell RK, Sanderson JD, Sans M, Satsangi J, Schreiber S, Simms LA, Sventoraityte J, Targan SR, Taylor KD, Tremelling M, Verspaget HW, De Vos M, Wijmenga C, Wilson CK, Zhao H, The International IBD Genetics Consortium, Silverberg MS, Annese V, Hakonarson H, Brant SR, Radford-Smith G, Mathew CG, Rioux JD, Schadt EE, Daly MJ, Franke A, Parkes M, Vermeire S, Barrett JC, Cho JH. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature, 491:119-124, 2012.
- Sarin R, Wu X, Abraham C. Inflammatory disease protective R381Q IL23R polymorphism results in decreased primary CD4+ and CD8+ human T cell functional responses. Proc Natl Acad of Sci USA, 108:9560-9565, 2011.
- Hedl, M and Abraham C. Distinct roles for Nod2 and autocrine IL-1beta in MDP-induced MAPK activation and cytokine secretion in human macrophages. J Biol Chem. 286:26440-26449, 2011.
- Abraham C and Medzhitov R. Interactions between the Host Innate Immune System and Microbes in Inflammatory Bowel Disease. Gastroenterology, 140:1729-1737, 2011
- Hedl M and Abraham C. Secretory mediators as a critical mechanism for Nod2-mediated tolerance in human macrophages. Gastroenterology, 140:231-241, 2011
- Abraham C and Cho J. Mechanisms of Disease: Inflammatory Bowel Disease. N Engl J Med. 361:56-68, 2009.