Mark Jay Shlomchik, MD, PhD
Campus: 200 Lothrop St
Office: W1052 BSTWR
Lab: E1000-4B - 8A BSTWR
Pittsburgh, PA 15261
- M.D., University of Pennsylvania Medical School, 1989
- PhD, University of Pennsylvania, 1989
- UPMC Endowed Professor and Chair, Department of Immunology
Our lab is interested in systemic autoimmune diseases, long-lived B cell immunity, and in immunopathogenesis. We are using transgenic and knockout mouse models to address the questions of how autoreactive B cells arise and what are the role(s) that these cells play in mediating autoimmune disease. We have also used genetic approaches to test the roles of CD11c+ and other myeloid cells in promoting murine lupus and autoreactive B cell activation. We continue to work regulatory role of TLR9 and stimulatory role of TLR7 in lupus, and to define how TLRs function in tissue-specific fashion, including recently defining the role of MyD88. During investigation of NETs in lupus we unexpectedly found a regulatory role for NADPH oxidase, whereas NETs were not required for SLE. Regarding B cell immunity, we have made recent insights into the mechanisms of cellular selection and differentiation in the germinal center, a site of rapid proliferation, mutation, and differentiation into memory cells. Strikingly, we found that BCR signaling was desensitized by elevated phosphatase activity in the GC, which we are actively investigating. We have identified novel subsets of memory B cells in mice and are studying their origins and function. Finally, we are investigating why memory T cells fail to cause graft-vs-host disease using a new TCR transgenic model.
- Good-Jacobson, K. L., E. Song, S. M. Anderson, A. H. Sharpe, and M. J. Shlomchik. 2012. CD80 expression on B cells regulates murine T follicular helper development, germinal center B cell survival and plasma cell generation, J. Immunol., 188:4217-4225. PMCID: PMC3331930
- Khalil, A., J.C. Cambier, and M.J. Shlomchik. 2012. B cell signal transduction in germinal center B cells is short-circuited by increased phosphatase activity. Science, 336:1178-81. PMCID: PMC3777391
- Campbell, A.M., M. Kashgarian, and M.J. Shlomchik. 2012. NADPH oxidase inhibits the pathogenesis of systemic lupus erythematosus. Science Translational Medicine, 4:157ra141. PMCID: PMC3704198
- Shlomchik, M. J. and F. Weisel. 2012. Germinal center selection and the development of memory B and plasma cells. Imm. Rev., 247: 52-63.
- Nickerson, K. M., S. R. Christensen, J. L. Cullen, W. Meng, E. T. Luning Prak, and M. J. Shlomchik. 2013. TLR9 promotes tolerance by restricting survival of anergic anti-DNA B cells yet is also required for their activation, J. Immunol., 190:1447-1456. PMCID: PMC3563726
- Teichmann, L. L., D. Schenten, R. Medzhitov, M. Kashgarian, and M. J. Shlomchik. 2013. Signals via the Adaptor MyD88 in B Cells and DCs make distinct and synergistic contributions to immune activation and tissue damage in Lupus. Immunity, 38:528-540. PMCID: PMC3638041
- Sweet, R. A., J. L. Cullen, and M.J. Shlomchik. 2013. Rheumatoid Factor B cell memory leads to rapid, switched antibody-forming cell responses. J. Immunol., 190: 1974-1981. PMCID: PC3578004.
- Nickerson, K. M., J. L. Cullen, M. A. Kashgarian, and M.J. Shlomchik. 2013. Exacerbated autoimmunity in the absence of TLR9 in MRL.Faslpr mice depends on Ifnar1. J. Immunol., online March 6, 2013. http://www.jimmunol.org/content/early/2013/03/06/jimmuol.1203525 [Featured article].PMCID: PMC3622185
- Conter, L.J., E. Song, M.J. Shlomchik, and M.M. Tomayko. 2014. CD73 expression is dynamically regulated in the germinal center and bone marrow plasma cells are diminished in its absence. PloS ONE 9:e92009. PMCID: PMC3963874
- Zuccarino-Catania, G. V., S. Sadanand, F.J. Weisel, M.T. Tomayko, H. Meng, S. Kleinstein, K.L. Good-Jacobson, and M.J. Shlomchik. 2014. Definition of functionally distinct memory B cell subsets based on expression of CD80 and PD-L2 but independent of antibody isotype. Nat. Immunol. 15:631-637.