Mark Jay Shlomchik, MD, PhD

Mark Jay Shlomchik, MD, PhD

Contact

Campus: 200 Lothrop St

Office: W1052 BSTWR

Lab: E1052 BSTWR

Pittsburgh, PA 15261

Ph: 412-648-8771

Fax: 412-383-8098

mshlomch@pitt.edu

Education

  • M.D., University of Pennsylvania Medical School, 1989
  • PhD, University of Pennsylvania, 1989

Academic Affiliation

  • UPMC Endowed Professor and Chair, Department of Immunology

About Research

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.

Selected Publications

1. Nickerson KM, Christensen SR, Cullen JL, Meng W, Luning Prak ET, Shlomchik MJ. TLR9 promotes tolerance by restricting survival of anergic anti-DNA B  cells yet is also required for their activation. J Immunol. 2013;190:1447-1456. PMCID: PMC3563726.
 
2. Teichmann LL, Schenten D, Medzhitov R, Kashgarian M, Shlomchik MJ. Signals via the Adaptor MyD88 in B Cells and DCs make distinct and synergistic contributions to immune activation and tissue damage in Lupus. Immunity. 2013;38:528-540. PMCID: PMC3638041.
 
3. Zuccarino-Catania GV, Sadanand S, Weisel FJ, Tomayko MT, Meng H, Kleinstein S, Good-Jacobson KL, Shlomchik MJ. Definition of functionally distinct memory B cell subsets based on expression of CD80 and PD-L2 but independent of antibody isotype. Nat Immunol. 2014; 15:631-637. PMCID: PMC4105703.
 
4. Teichmann LL, Cullen J, Kashgarian M, Dong C, Craft J, Shlomchik MJ, Local triggering of the ICOS coreceptor by CD11c+ myeloid cells drives organ inflammation in lupus. Immunity. 2015;42:552-565.  PMCID: PMC4456685.
 
5. Di Niro R, Elsner RA, Vander Heiden JA, Trivedi N, Lee S-J, Bannock JM, Gupta N, Kleinstein SH, Vigneault F, Gilbert TJ, Meffre E, McSorley SJ, Shlomchik MJ. The B cell response to Salmonella: promiscuous B cell recruitment for early antibody production followed by extrafollicular affinity maturation. Immunity. 2015;43:120-131.  PMCID: PMC4523395.
 
6. Weisel FW, Chikina M, Shlomchik MJ. A temporal switch in the germinal center determines differential output of memory B and plasma cells. Immunity. 2016;44: 116-130. PMCID: PMC4724390.
 
7. Ols ML, Cullen JL, Turqueti-Neves A, Giles J, Shlomchik MJ. Dendritic cells regulate extrafollicular autoreactive B cells via T cells expressing Fas and Fas ligand. Immunity. 2016; 45:1052-65. PMCID: PMC5112117.
 
8. Giles JR, Turqueti-Neves A, Marshak-Rothstein A, Shlomchik MJ. Autoreactive helper T cells alleviate the need for intrinsic TLR signaling in autoreactive B cell activation. JCI Insight. 2017;2(4):e90870. doi:10.1172/jci.insight.90870. PMCID: PMC5313065.
 
9. Gordon RA, Herter JM, Rosetti F, Campbell AM, Nishi H, Kashgarian M, Bastacky SI, Marinov A, Nickerson KM, Mayadas TN, Shlomchik MJ. Lupus and Proliferative Nephritis are PAD4 Independent in Murine Models. JCI Insight. 2017;2(10):e92926. doi:10.1172/jci.insight. 92926. PMCID: PMC5436537.
 
10. Luo W, Weisel F, Shlomchik  MJ. B Cell receptor and CD40 signaling Are rewired for synergistic induction of the c-Myc transcription factor in germinal center B cells. Immunity. 2018;48:313-326. PMCID: PMC5821563.
 
11. Tilstra JS, Avery L, Menk AV, Gordon RA, Smita S, Kane LP, Chikina M, Delgoffe GM, Shlomchik MJ. Kidney-infiltrating T cells in murine lupus nephritis are metabolically and functionally exhausted. J Clin Inv. 2018. In press.