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Research > Faculty By Division > Barry Sleckman, MD, PhD

Conan Professor, Pathology and Immunology
Chief, Division of Laboratory and Genomic Medicine
CSRB, 7th Floor, Room 7749
Office: (314) 747-8235
Lab: (314) 747-8237
E-mail: sleckman@wustl.edu
Web-site: http://pathology.wustl.edu/labs/sleckman/
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Research

The work in our laboratory is focused in two areas:

Mechanisms of DNA double strand break repair and lymphomagenesis: DNA double strand breaks (DSBs) are generated during several physiologic processes, including during the assembly of lymphocyte antigen receptor genes. During lymphocyte development the RAG proteins introduce DNA DSBs at the border of gene segments in antigen receptor loci and these DSBs are joined bringing the gene segments together forming a complete antigen receptor gene. If these DNA DSBs are not correctly repaired they can be aberrantly resolved, for example, as chromosomal translocations, which can lead to cellular transformation and lymphomagenesis. A major focus of our lab is to identify the proteins that prevent the aberrant resolution of DNA DSBs during lymphocyte antigen receptor gene assembly. How these proteins function and whether they are generally involved in the repair of DNA DSBs generated by genotoxic agents is also a focus of the lab.

Defining the genetic program of developing lymphocytes: All mature B and T lymphocytes develop from a common lymphocyte progenitor. Developing lymphocytes transit discrete developmental stages as they differentiate into mature T or B lineage cells. Successful transit of these stages requires the initiation of specific genetic programs at each developmental stage. A major focus of the lab is to use gene-targeting technology to generate genetically modified mice that will allow us to elucidate the genetic program of lymphocytes at distinct stages of development. Ultimately, we will determine how the expression of these genes is regulated and how expression of proteins, encoded by these genes, promotes normal lymphocyte development.

Service to the Department

2005 - PresentMedical Director, Clinical Immunology Laboratory

Service to the University

2006 - PresentDirector, Graduate Program in Immunology
2005 - PresentCommittee on the Academic Evaluation of Students
2003 - PresentCommittee on Professionalism, Washington University School of Medicine
2003 - 2005Animal Studies Committee, Washington University
2000 - PresentLecturer, Medical Immunology, Washington University School of Medicine
2000 - PresentCourse Director, Molecular Immunology, Washington University School of Medicine
1999 - 2006Course Co-director, Advanced Topics in Immunology, Washington University
1999 - PresentLecturer, Foundations in Immunology, Washington University

DBBS Graduate Program Affiliation

Immunology Program

Diagnostic Expertise

Genetic basis of immune deficiency disorders

Clinical Interest

Laboratory and Genomic Medicine - Immunology

Selected Publications

Khor B, Bredemeyer AL, Huang C, Turnbull IR, Evans R, Maggi LB, White JM, Walker LM, Carnes K, Hess. Proteasome activator PA200 is required for normal spermatogenesis. Mol. Cell. Biol. 2006; 26: 2999-3007, 2006 Abstract

Bredemeyer AL, Sharma GG, Huang C, Helmink BA, Walker LM, Khor KC, Nuskey B, Sullivan KE, Pandita TK, Bassing CH, Sleckman BP. ATM stabilizes DNA double strand break complexes during V(D)J recombination. Nature 2006 442:466-470, 2006 Abstract

Huang CY, Sleckman BP, Kanagawa O. Revision of TCRa chain genes is required for normal T lymphocyte development. Proc. Natl. Acad. of Sci. (USA). 2005; 102:14356-1, 2005 Abstract

Kim J, White JM, Shaw AS, Sleckman BP. MAP Kinase p38 is Dispensable for Lymphocyte Development and Proliferation. J Immunol 174:1239-1244, 2005, 2005 Abstract

Khor B, Sleckman BP. Intra- and Inter-allelic ordering of T cell receptor chain gene assembly. Eur J Immunol 35:964-970, 2005, 2005 Abstract

Jackson A, Kondilis HD, Khor B, Sleckman BP, Krangel M. Regulation of T cell receptor b allelic exclusion at a level beyond accessibility. Nat Immunol 6:189-197, 2005, 2005 Abstract

Khor B, Wehrly TD, Sleckman BP. Chromosomal excision of TCRd chain genes is dispensable for ab T cell lineage commitment. Int Immunol Jan 10 [Epub ahead of print], 2005, 2005 Abstract

Hughes MM, Tillman RE, Wehrly TD, White JM, Sleckman BP. The B12/23 restriction is critically dependent on the recombination signal nonamer and spacer sequences. J Immunol 171:6604-6610, 2003, 2003 Abstract

Hughes MM, Yassai M, Sedy JR, Wehrly TD, Huang CY, Kanagawa O, Gorski J, Sleckman BP. T cell receptor CDR3 loop length repertoire is determined primarily by features of the V(D)J Recombination reaction. Eur J Immunol 33:1568-1575, 2003 Abstract

Tillman RE, Wooley AL, Khor B, Wehrly TD, Little CA, Sleckman BP. Cutting Edge: Targeting of V to D rearrangement by RSSs can be mediated by the V(D)J recombinase in the absence of additional lymphoid specific factors. J Immunol 170:5-9, 2003 Abstract

Tillman RE, Wooley AL, Hughes MM, Wehrly TD, Swat W, Sleckman BP. Restrictions limiting the generation of DNA double stranded breaks during chromosomal V(D)J Recombination. J Exp Med 195:309-316, 2002 Abstract

Khor B, Sleckman BP. Allelic exclusion at the TCRb locus. Curr Opin Immunol 14:230-234, 2002 Abstract

Bassing CH, Alt FW, Hughes MM, D'Auteuil M, Wehrly TD, Woodman BB, Gartner F, White JM, Davidson L,. Recombination signal sequences restrict chromosomal V(D)J recombination beyond the 12/23 rule. Nature 405:583-586, 2000 Abstract

Sleckman BP, Bassing CH, Hughes MM, Okada A, D'Auteuil M, Wehrly T, Woodman BB, Davidson L, Chen J,. Mechanisms that direct ordered assembly of T cell receptor b locus V, D, and J gene segments. Proc Natl Acad Sci USA 97:7975-7980, 2000 Abstract

Pappu R, Cheng AM, Li B, Gong Q, Chiu C, Griffin N, White M, Sleckman BP, Chan AC. Requirement for B Cell linker protein (BLNK) in B cell development. Science 286:1949-1954, 1999 Abstract

Hernandez-Munain C, Sleckman BP, Krangel MS. A developmental switch from TCR d to TCR a enhancer function during thymocyte development. Immunity 10:723-733, 1999 Abstract

Sleckman BP, Khor B, Monroe R, Alt FW. Assembly of T cell receptor variable region genes exhibits allelic inclusion. J Exp Med 188:1465-1471, 1998 Abstract

Sleckman BP, Bardon CG, Ferrini R, Davidson L, Alt FW. Function of the TCR enhancer in and T cells. Immunity 7:505-515, 1997 Abstract


Current Trainees

Eric Gapud
Beth Helmink
Andrea Wooley

Past Trainees

Maureen Hughes
Bernard Khor
Robert Tillman
Graduate Students
Grace Kao

Postdoctoral Fellows
Ching-Yu Huang, PhD