Marcus Clark, M.D.
B Cell Development and Activation
Our laboratory has a long-standing interest in B cell antigen receptor (BCR) signaling and BCR dependent processes regulate specific cell fate decisions. In the bone marrow, we have been working to understand how signals initiated through the BCR, in conjunction with those delivered through the IL-7 receptor, coordinate cell cycle progression with immunoglobulin light chain recombination. In the periphery, we have focused on the molecular mechanisms of receptor endocytosis and endocytic trafficking and how these mechanisms influence BCR trafficking and cell fate. As is the case with our studies of lymphopoiesis, we have derived novel in vivo models, and have performed directed in vitro studies, to obtain definitive insights into these processes. In our newest project area, we are applying our knowledge of B cell biology to understanding how in situ adaptive immune responses drive tubulointerstitial inflammation in human lupus nephritis.
Ochiai K, Maienschein-Cline M, Mandal M, Triggs JR, Bertolino E, Sciammas R, Dinner AR, Clark MR and Singh H. 2012. The regulatory and molecular logic of IL-7R and pre-BCR signaling in B cell development. In press, Nature Immunology.
Mandal M, Powers SE, Maienchein-Cline M, Bartom ET, Hamel KM, Kee BL, Dinner AR and Clark MR. 2011. Epigenetic repression of the Igk locus by STAT5-mediated recruitment of the histone methyltransferase Ezh2. In press, Nature Immunology.
Clark MR. 2011. Flippin’ Lipids. Nature Immunology 12:373-375.
Chang, A., Henderson S, Liu N, Guttikonda R, Hsieh C, Utset T, MD, Meehan S, Quigg R, Meffre E and Clark MR. 2011. In situ B cell mediated immune responses and tubulointerstitial inflammation in human lupus nephritis. J Immunol. 186:1849-1860.
Clark MR, Tanaka A, Powers SE and Veselits M. 2011. Receptors, subcellular compartments and the regulation of peripheral B cell responses: The illuminating state of anergy. Mol Immunol. 48:1281-1286.
Alegre M-L, Cambier J, and Clark MR. 2009. Endocytic sequestration of the B cell antigen receptor and toll-like receptor 9 in anergic cells. Proc Natl Acad Sci, USA., 106(15):6260-7.
Mandal M, Powers SE, Ochiai K, Georgopoulos K, Kee BL, Singh H, Clark MR. 2009, Ras orchestrates exit from the cell cycle and light-chain recombination during early B cell development. Nature Immunology. Oct;10(10):1110-7.
Mandal M, Crusio KM, Meng F, Liu S, Kinsella M, Clark MR, Takeuchi O, Aifantis I. 2008. Regulation of lymphocyte progenitor survival by the proapoptotic activities of Bim and Bid. Proc Natl Acad Sci, USA. 105:20840-20845.
Zhang M, Veselits M, O'Neill S, Hou P, Reddi AL, Berlin I, Ikeda M, Nash PD, Longnecker R, Band H and Clark MR. 2007. Ubiquitinylation of Ig-beta dictates the endocytic fate of the B cell antigen receptor. J Immunol 179: 4435-4443.
Hou P, Araujo E, Zhao T, Massenburg D, Veselits M, Doyle C, Dinner AR and Clark MR. 2006 B cell antigen receptor signaling and internalization are mutually exclusive events. PLoS Biology e200.
Gomez TS, McCarney SD, Labno CM, Comiskey EO, Nolz JC, Carrizosa E, Clark MR, Billadeau DD, Burkhardt JK. 2006. A functional role for HS1 in controlling actin filament stabilization at the immunological synapse. Immunity. 24:741-752.
Cooper AB, Sawai CM, Sicinska E, Powers SE, Sincinski P, Aifantis I* and Clark MR*. 2006. A unique role for cyclin D3 in early B cell development. Nature Immunology 7:489-497 *co-senior and corresponding authors.
Wang LD, Lopes J, Cooper AB, Dang-Lawson M, Matsuuchi L and Clark MR. 2004. Selection of B lymphocytes in the periphery is determined by the functional capacity of the B cell antigen receptor. Proc Natl Acad Sci 101: 1027-1032.
Faculty and Research