Mark S. Schlissel Provost, Professor of Biology

Dr. Schlissel was named provost of Brown University in July 2011.  As Brown’s chief academic officer, the provost is responsible for all academic programmatic and budgetary functions within the College, the Graduate School, the School of Medicine and the School of Engineering, as well as the libraries, research institutes and centers. He supervises the Deans and academic Vice Presidents, oversees admission and information systems, and is the principal deputy to President Christina Paxson. The Provost provides daily management of the institution and directs overall strategic planning.

A graduate of Princeton University (A.B., summa cum laude, 1979, Biochemical Sciences), Schlissel earned both M.D. and Ph.D. degrees at the Johns Hopkins University School of Medicine (1986, Physiological Chemistry). He did his residency training in internal medicine at Hopkins Hospital and conducted postdoctoral research as a Bristol-Myers Cancer Research Fellow under David Baltimore at the Massachusetts Institute of Technology, Whitehead Institute.

Schlissel began his career as a faculty member at the Johns Hopkins University School of Medicine in 1991, where he earned a number of awards and fellowships for his research and teaching. He moved to the Department of Molecular and Cell Biology at the University of California–Berkeley in 1999 as Associate Professor, advancing to Full Professor in 2002. He taught undergraduate and graduate courses in immunology as well as a large introductory course in biology for life science majors.

Schlissel’s research has focused on the developmental biology of B lymphocytes, the cell type in the immune system that secretes antibodies. His work has led to a detailed understanding of genetic factors involved in the production of antibodies and how mistakes in that process can lead to leukemia and lymphoma. He is the author or co-author of nearly 100 scientific papers and has trained twenty successful doctoral candidates in his lab.

Schlissel was UC Berkeley’s Dean of Biological Sciences in the College of Letters & Science and held the C.H. Li Chair in Biochemistry until his appointment as Brown’s Provost.  He served as Vice Chair of the Molecular and Cell Biology Department from 2002 to 2007. Nationally, he has served as member (2002-04) and chair (2004-06) of the Immunobiology Study Section at the National Institutes of Health and on the Howard Hughes Medical Institute’s Scientific Review Board (2006-2011). Schlissel was elected to the American Society of Clinical Investigators in 1998 and the American Association of Physicians in 2013. He has been a member of the American Association of Immunologists since 1992 and was named a Fellow of the American Association for the Advancement of Science in 2013. He has helped organize major international scientific meetings and is a frequent seminar speaker at universities through the United States.

Schlissel is married, with four children. His wife Monica is an environmental and energy lawyer with a large national law firm.

Research Areas

research overview

The Regulation of Antigen Receptor Gene Rearrangement and Lymphocyte Development. Immunoglobulin (Ig) and T cell receptor (TCR) genes are assembled during lymphocyte development from their component gene segments by a novel series of highly regulated DNA rearrangement reactions known as V(D)J recombination. (Figure 1) Understanding the regulation of gene rearrangement is important because its products (Ig and TCR molecules) control the development and function of B and T cells and because errors in the process can result in leukemia, lymphoma, or immunodeficiency disease. (Figure 2) A single enzyme complex known as the V(D)J recombinase is required for the rearrangement of each of the seven complex genetic loci encoding antigen receptor chains. The recombinase recognizes a highly conserved DNA sequence, the RSS, and introduces a dsDNA break. The DNA break repair machinery expressed in all cells then generates various molecular joints. (Figure 3) Our data suggests that transcription or transcription factor binding targets the recombination reaction to a particular genetic locus at the appropriate stage of development. My lab is interested in determining the molecular basis of this link between transcription and gene rearrangement during B cell development and in understanding how a common recombinase recognizing a conserved DNA element can result in highly regulated patterns of gene rearrangement. (Figure 4) In addition, we are interested in the reaction mechanism of the V(D)J recombinase.

          Using bone marrow, thymus and fetal liver from wild-type or recombination-deficient Ig or TCR transgenic mice, we can purify primary lymphoid cells "frozen" at different stages of development. In addition, we can use gene targeting technologies in embryonic stem cells to introduce specific mutations into key genes. We are analyzing signal transduction pathways, patterns of transcription factor activity and chromosomal DNA-protein interactions to determine the critical receptors, protein factors and DNA sequences involved in the regulation of B and T cell development and Ig and TCR gene rearrangement. We have also devised a series of novel assays which detect recombination reaction intermediates and are using them to study both the developmental regulation and reaction mechanism of the V(D)J recombinase. (Figure 5) Recently, we devised an in vitro assay system which recapitulates the developmental regulation of V(D)J recombination and are engaged in the dissection of its molecular components. (Figure 6)


Current Projects
        Active projects in the lab include 1) an analysis of the influence of chromatin structure on the targeting of V(D)J recombination; 2) reconstitution of regulated V(D)J recombination in vitro using purified recombinase components and long DNA templates; 3) promoter and enhancer activities involved in the transcriptional regulation of genes encoding the V(D)J recombinase (RAG1 and RAG2); 4) the use of gene targeting to determine the function of various domains of RAG1 and RAG2; 5) identifying transcription factors and DNA sequences involved in the regulated activation of rearrangement at the Ig kappa locus and TCR beta locus; 6) determining the role of transcriptional enhancer sequences in the targeting of recombination and in coding joint formation; 7) elucidating the rules governing receptor editing; 8) studying the mechanism and determining the frequency of transposition events catalyzed by the recombinase during lymphocyte development; and 9) determining the role of the c-Abl protein tyrosine kinase in lymphocyte development and cellular transformation

research statement

82.       Amin, R.H., D. Cado, H. Nolla, D. Huang, S.A. Shinton, Y. Zhou, R.R. Hardy, and M.S. Schlissel. 2009. Biallelic, ubiquitous transcription from the distal germline Ig{kappa} locus promoter during B cell development. Proc Natl Acad Sci U S A 106:522-527.

83.       Schlissel, M.S., D. Schulz, and C. Vettermann. 2009. A histone code for regulating V(D)J recombination. Mol Cell 34:639-640.

84.       Kuo, T.C., and M.S. Schlissel. 2009. Mechanisms controlling expression of the RAG locus during lymphocyte development. Curr Opin Immunol 21:173-178.

85.       Derudder, E., E.J. Cadera, J.C. Vahl, J. Wang, C.J. Fox, S. Zha, G. van Loo, M. Pasparakis, M.S. Schlissel, M. Schmidt-Supprian, and K. Rajewsky. 2009. Development of immunoglobulin lambda-chain-positive B cells, but not editing of immunoglobulin kappa-chain, depends on NF-kappaB signals. Nat Immunol 10:647-654.

86.       Cadera, E.J., F. Wan, R.H. Amin, H. Nolla, M.J. Lenardo, and M.S. Schlissel. 2009. NF-{kappa}B activity marks cells engaged in receptor editing. J Exp Med 206:1803-1816.

87.       Brightbill, H., and M.S. Schlissel. 2009. The effects of c-Abl mutation on developing B cell differentiation and survival. Int Immunol 21:575-585.

88.       Vettermann, C., and M. S. Schlissel. 2010. Allelic exclusion of immunoglobulin genes: models and mechanisms. Immunol Rev 237:22-42.

89.       Wilson, M. K., S. M. McWhirter, R. H. Amin, D. Huang, and M. S. Schlissel. 2010. Abelson virus transformation prevents TRAIL expression by inhibiting FoxO3a and NF-kappaB. Mol Cells 29:333-341.

90.       Kuo, T. C., J. E. Chavarria-Smith, D. Huang, and M. S. Schlissel. 2011. Forced expression of cyclin-dependent kinase 6 confers resistance of pro-B acute lymphocytic leukemia to gleevec treatment. Molecular and cellular biology 31:2566-2576.

91.       Schlissel, M. S. 2010. Epigenetics Drives RAGs to Recombination Riches. Cell 141:400-402.

92.       Sukumar, S., and M. S. Schlissel. 2011. Receptor editing as a mechanism of B cell tolerance. Journal of immunology 186:1301-1302.

93.       Degner, S.C., J. Verma-Gaur, T.P. Wong, C. Bossen, G.M. Iverson, A. Torkamani, C. Vettermann, Y.C. Lin, Z. Ju, D. Schulz, C.S. Murre, B.K. Birshtein, N.J. Schork, M.S. Schlissel, R. Riblet, C. Murre, and A.J. Feeney. 2011. CCCTC-binding factor (CTCF) and cohesin influence the genomic architecture of the Igh locus and antisense transcription in pro-B cells. Proc. Natl. Acad. Sci USA 108:9566-9571.

94.       Guo, C., Yoon, H.S., Franklin, A., Jain, S., Ebert, A., Cheng, H.L., Hansen, E., Despo, O., Bossen, C., Vettermann, C., Bates, J. G., Richards, N., Myers, D., Patel, H., Gallagher, M., Schlissel, M. S., Murre, C., Busslinger, M., Giallourakis, C. C., Alt, F. W. 2011. CTCF-binding elements mediate control of V(D)J recombination. Nature 477: 424-430.

95.       Schulz, D., Vassen, L., Chow, K.T., McWhirter, S.M., Amin, R.H., Moroy, T., and Schlissel, M.S. 2012. Gfi1b negatively regulates Rag expression directly and via the repression of FoxO1. J Exp Med 209: 187-199.

96.       Bednarski, J.J., Nickless, A., Bhattacharya, D., Amin, R.H., Schlissel, M.S., and Sleckman, B.P. 2012. RAG-induced DNA double-strand breaks signal through Pim2 to promote pre-B cell survival and limit proliferation. J Exp Med 209: 11-17.

97.       Garcia, P.B., Cai, A., Bates, J.G., Nolla, H., and Schlissel, M.S. (2012). miR290-5p/292-5p activate the immunoglobulin kappa locus in B cell development. PLoS One 7, e43805.

98.       Bates, J.G., Salzman, J., May, D., Garcia, P.B., Hogan, G.J., McIntosh, M., Schlissel, M.S., and Brown, P.O. (2012). Extensive gene-specific translational reprogramming in a model of B cell differentiation and Abl-dependent transformation. PLoS One 7, e37108.

99.       Chow, K.T., Timblin, G.A., McWhirter, S.M., and Schlissel, M.S. (2013). MK5 activates Rag transcription via Foxo1 in developing B cells. J Exp Med 210, 1621-1634.

100.     Schlissel, M. (2013). Immunology: B-cell development in the gut. Nature 501, 42-43.

101.     Timblin, G.A., and Schlissel, M.S. (2013). Ebf1 and c-Myb repress Rag transcription downstream of Stat5 during early B cell development. J Immunol 191, 4676-4687.

102.     Chow, K.T., Schulz, D., McWhirter, S.M., and Schlissel, M.S. (2013). Gfi1 and Gfi1b repress Rag transcription in plasmacytoid dendritic cells in vitro. PLoS One 8, e75891.