Clara Abraham, MD
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 regulating intestinal immune homeostasis and the dysregulation that occurs with intestinal inflammation 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. We seek to understand both innate and adaptive immune pathways that contribute to these diseases. Further, we utilize the genetic discoveries in inflammatory bowel disease to guide these studies, such that we focus on understanding the immunological consequences of genetic variants (e.g. NOD2, IL23/Th17 pathway) implicated in either increasing or decreasing the likelihood of developing human inflammatory bowel disease.
Key Phrases: Regulation of the intestinal immune system; Genetics and immunobiology of inflammatory bowel disease; host:microbe interactions.
- MD, University of Chicago Pritzker School of Medicine, 1989
- BS, University of Illinois at Urbana-Champaign, 1985
- Hedl M, Yan J, and Abraham C. Cell Rep. 16:2442-2455, 2016
- Lahiri A, Hedl M and Abraham C. MTMR3 risk allele enhances innate receptor-induced signaling and cytokines by decreasing autophagy and increasing caspase-1 activation. Proceedings of the National Academy of Science, 112:10461-10466, 2015
- Hedl M and Abraham C. A TPL2 (MAP3K8) disease risk polymorphism increases TPL2 expression thereby leading to increased pattern recognition receptor-initiated caspase-1 and -8 activation, signalling and cytokine secretion. Gut, epub 7/27/15.
- Zheng S, Hedl M, Abraham C. Twist1 and Twist2 contribute to cytokine downregulation following chronic NOD2 stimulation of human macrophages through the coordinated regulation of transcriptional repressors and activators. Journal of Immunology. 195:217-226, 2015.
- Wu X, Lahiri A, Sarin R, Abraham C. T cell-extrinsic CD18 attenuates antigen-dependent CD4+ T cell activation in vivo. Journal of Immunology. 194:4122-4129, 2015.
- Zheng S, Hedl M, Abraham C. TAM receptor-dependent regulation of SOCS3 and MAPKs contributes to pro-inflammatory cytokines downregulation following chronic NOD2 stimulation of human macrophages. Journal of Immunology. 194(4):1928-37, 2015.
- Hedl M and Abraham C. A TNFSF15 Disease-Risk Polymorphism Increases Innate Receptor Signaling Through Caspase-8-Induced IL-1. Proceedings of the National Academy of Science, 111:13451-13456, 2014.
- Lahiri A and Abraham C. Activation of Pattern Recognition Receptors Upregulates Metallothioneins, Thereby Increasing Intracellular Accumulation of Zinc, Autophagy, and Bacterial Clearance by Macrophages. Gastroenterology, 147:835-846, 2014.
- Hedl M, Lahiri A, Ning K, Cho JH, Abraham C. Pattern Recognition Receptor Signaling in Human Dendritic Cells is Enhanced by ICOS Ligand and Modulated by the Crohn’s Disease ICOSLG Risk Allele. Immunity, 40:734-746, 2014.
- Wu X, Lahiri A, Haines, GK III, Flavell RA, Abraham C. NOD2 regulates CXCR3-dependent CD8+ T cell accumulation in intestinal tissues with acute injury. J Immunol. 192:3409-3418, 2014.
- Zheng S and Abraham C. NFkB1 inhibits NOD2-induced cytokine secretion through ATF3-dependent mechanisms. Mol Cell Biol. 33:4857-4871. 2013.
- 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.
- 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
- Abraham C and Cho J. Mechanisms of Disease: Inflammatory Bowel Disease. N Engl J Med. 361:56-68, 2009.