Mark J. Shlomchik, M.D., Ph.D.

Chair of Department of Immunology, University of Pittsburgh School of Medicine

Dr. Shlomchik received his medical and doctoral degrees in 1989 from the University of Pennsylvania, where he also completed residency training in pathology and laboratory medicine. After postdoctoral work at Fox Chase Cancer Center in Philadelphia, he joined the faculty at Yale University, rising to the rank of full professor in 2004. In 2013 Dr. Shlomchik was selected to head the University of Pittsburgh School of Medicine’s Department of Immunology.

In the area of lupus, Dr. Shlomchik’s work was among the first to elucidate the roles of B lymphocytes and Toll-like receptors in promoting disease. Both of these are now targets of drugs that are either approved or in development to treat autoimmune disorders in patients. In October 2012, Dr. Shlomchik’s team showed in Science Translational Medicine that an enzyme complex called NADPH oxidase, or NOX2, which plays an important role in the body’s resistance to bacteria and fungi, is also necessary to curb genetic predisposition to lupus. In addition to autoimmunity, B-cell immune responses and how vaccines elicit protective antibodies, Dr. Shlomchik has worked on bone marrow transplantation, where some of his findings have also resulted in an ongoing clinical trial.

Dr. Shlomchik's current lab is interested in systemic autoimmune diseases, long-lived B cell immunity, and in immunopathogenesis. They are using transgenic and knockout mouse models to address questions of how autoreactive B cells arise and what are the role(s) that these cells play in mediating autoimmune disease. They have also used genetic approaches to test the roles of CD11c+ and other myeloid cells in promoting murine lupus and autoreactive B cell activation. They continue to work on the 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 they unexpectedly found a regulatory role for NADPH oxidase, whereas NETs were not required for SLE. Regarding B cell immunity, they 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. They have identified novel subsets of memory B cells in mice and are studying their origins and function. They also investigate why memory T cells fail to cause graft-vs-host disease using a new TCR transgenic model.

Selected Publications:

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. [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.

Sai Reddy, Ph.D.

Sai Reddy has been a tenure-track Assistant Professor at ETH Zurich in the Dept. of Biosystems Science & Engineering since the beginning of 2012. His research group focuses on immunogenomics by next-generation sequencing and bioinformatic analysis of immune repertoires and reprogramming of immune cells by genome engineering for applications in biotechnology, vaccination, and immunotherapy. Prof. Reddy holds B.S. (2003) and M.S. (2004) degrees from Northwestern University (Evanston, IL, USA) in Biomedical Engineering. He completed his Ph.D. thesis at Ecolé Polytechnique Féderale de Lausanne (EPFL, Switzerland) in Bioengineering and Biotechnology in 2008. Prof. Reddy moved to University of Texas, Austin (USA) for his post-doctoral fellowship (2008-2011), where he worked on protein and antibody engineering.

Selected Publications:

Waldmeier L, Hellmann I, Gutknecht CK, Wolter FI, Cook SC, Reddy ST, Grawunder
U, Beerli RR. Transpo-mAb display: Transposition-mediated B cell display and
functional screening of full-length IgG antibody libraries. MAbs. 2016
May-Jun;8(4):726-40. doi: 10.1080/19420862.2016.1160990. Epub 2016 Mar 17. PubMed
PMID: 26986818.

Khan TA, Friedensohn S, Gorter de Vries AR, Straszewski J, Ruscheweyh HJ,
Reddy ST. Accurate and predictive antibody repertoire profiling by molecular
amplification fingerprinting. Sci Adv. 2016 Mar 11;2(3):e1501371. doi:
10.1126/sciadv.1501371. eCollection 2016 Mar. PubMed PMID: 26998518; PubMed
Central PMCID: PMC4795664.

Greiff V, Bhat P, Cook SC, Menzel U, Kang W, Reddy ST. A bioinformatic
framework for immune repertoire diversity profiling enables detection of
immunological status. Genome Med. 2015 May 28;7(1):49. doi:
10.1186/s13073-015-0169-8. eCollection 2015. PubMed PMID: 26140055; PubMed
Central PMCID: PMC4489130.

Schanz M, Liechti T, Zagordi O, Miho E, Reddy ST, Günthard HF, Trkola A, Huber
M. High-throughput sequencing of human immunoglobulin variable regions with
subtype identification. PLoS One. 2014 Nov 3;9(11):e111726. doi:
10.1371/journal.pone.0111726. eCollection 2014. PubMed PMID: 25364977; PubMed
Central PMCID: PMC4218849.

Haessler U, Reddy ST. Using next-generation sequencing for discovery of
high-frequency monoclonal antibodies in the variable gene repertoires from
immunized mice. Methods Mol Biol. 2014;1131:191-203. doi:
10.1007/978-1-62703-992-5_12. PubMed PMID: 24515467.

Reddy ST, Ge X, Miklos AE, Hughes RA, Kang SH, Hoi KH, Chrysostomou C,
Hunicke-Smith SP, Iverson BL, Tucker PW, Ellington AD, Georgiou G. Monoclonal
antibodies isolated without screening by analyzing the variable-gene repertoire
of plasma cells. Nat Biotechnol. 2010 Sep;28(9):965-9. doi: 10.1038/nbt.1673.
Epub 2010 Aug 29. PubMed PMID: 20802495.

George Church, Ph.D.

Dr. Church is Professor of Genetics at Harvard Medical School and Director of the Center for Computational Genetics. With degrees from Duke University in chemistry and zoology, he co-authored research on 3D-software and RNA structure with Sung-Hou Kim. His Ph.D. from Harvard in biochemistry and molecular biology with Wally Gilbert included the first direct genomic sequencing method in 1984; initiating the Human Genome Project then as a Research Scientist at newly-formed Biogen Inc. and a Monsanto Life Sciences Research Fellow at UCSF.  He invented the broadly-applied concepts of molecular multiplexing and tags, homologous recombination methods, and array DNA synthesizers. Technology transfer of automated sequencing and software to Genome Therapeutics Corp. resulted in the first commercial genome sequence (the human pathogen, H. pylori, 1994).  He has served in advisory roles for 12 journals, 5 granting agencies and over 20 biotech companies.  Current research focuses on integrating biosystems-modeling with personal genomics and synthetic biology.​

Yen-Ming Hsu, Ph.D.

Dr. Yen-Ming Hsu is the CEO of AB Biosciences, Inc. at Boston, Massachusetts.

Prior to co-founding AB Biosciences, Dr. Hsu headed a protein engineering group in the Research Department of Biogen-Idec, Cambridge, Massachusetts, where he spent over two decades in developing a dozen therapeutic antibodies for immunological and oncological indications. Prior to joining Biogen-Idec (then Biogen), Dr. Hsu was a post-doctoral fellow in Professor Guido Guidotti’s lab at the Cellular and Molecular Biochemistry, Harvard, where he discovered the 2nd isoform of the Na+-K+ ATPase in the axolemma of rat brain stem. Dr. Hsu obtained his Ph.D. in Biochemistry at John L. Wang’s, Michigan State University, where he studied the density-dependent growth of monolayer cell cultures.

As an accomplished biochemist, Dr. Hsu has designed over a hundred recombinant soluble ligand and receptor proteins from their membrane anchored counterparts as part of his toolkit for developing therapeutic biologics targeting these surface molecules. His research area focuses on proteins of TNF receptor and ligand super-families, costimulatory/checkpoint proteins as well as CD molecules of adaptive and innate immunity. His biologics developmental efforts focus on antibody molecules and their derivatives. Dr. Hsu’s in-depth knowledge and hands-on experience in the structures and functions of immunoglobulin molecules are invaluable for the development of antibody drugs. He has 43 peer-reviewed publications and 27 granted patents.