Positions

Overview

  • Barry Sleckman completed his M.D. and a Ph.D. in immunology at Harvard Medical School, followed by a residency in internal medicine and a fellowship in infectious diseases at Brigham and Women's Hospital. After completing his post-doctoral training in molecular immunology in the laboratory of Dr. Frederick Alt at Boston Children's Hospital, Sleckman started his own laboratory in 1998 as an Assistant Professor in the Department of Pathology and Immunology at the Washington University School of Medicine and moved to Weill Cornell in 2015. Then in 2020, Barry relocated his laboratory to UAB, where he now serves as the Director of the O’Neal Comprehensive Cancer Center.

    Sleckman’s laboratory has focused on elucidating the molecular pathways required for normal lymphocyte development and on understanding how DNA repair and DNA damage response pathways regulate lymphocyte development and function, preserve genome stability and prevent lymphocyte transformation. His laboratory was the first to show that DNA damage responses provide signals that regulate cell-type specific processes that are not required for DNA repair. In addition, his lab discovered DNA damage response pathways that do not function in normal DNA repair. Rather, they function to prevent unrepaired DSBs from being aberrantly repaired as potentially dangerous chromosomal translocations and deletions. Sleckman has been elected to the American Society of Clinical Investigation and the Association of American Physicians, and he is a fellow in the American Academy for the Advancement of Science.
  • Selected Publications

    Academic Article

    Year Title Altmetric
    2020 Loss of H3K36 Methyltransferase SETD2 Impairs V(D)J Recombination during Lymphoid DevelopmentiScience.  23. 2020
    2020 Erratum: The Histone Chaperones ASF1 and CAF-1 Promote MMS22L-TONSL-Mediated Rad51 Loading onto ssDNA during Homologous Recombination in Human Cells (Molecular Cell (2018) 69(5) (879–892.e5), (S1097276518300601), (10.1016/j.molcel.2018.01.031))Molecular Cell.  77:1153. 2020
    2020 DNA damage responses in murine Pre-B cells with genetic deficiencies in damage response genesCell Cycle.  19:67-83. 2020
    2019 Regional gene repression by DNA double-strand breaks in G1 phase cellsMolecular and Cellular Biology.  39. 2019
    2019 At the intersection of DNA damage and immune responsesNature Reviews Immunology.  19:231-242. 2019
    2019 XLF and H2AX function in series to promote replication fork stability 2019
    2018 A Path(way) to Keeping Your Synapses on an Even KeelNeuron.  100:1013-1014. 2018
    2018 Cell circuits between B cell progenitors and IL-7+ mesenchymal progenitor cells control B cell developmentJournal of Experimental Medicine.  215:2586-2599. 2018
    2018 Erratum for Franco et al., “A novel secreted protein, myr1, is central to toxoplasma’s manipulation of host cells” (mBio, (2018) 7(1), e02231-15, 10.1128/mBio.02231-15)mBio.  9. 2018
    2018 High-Throughput Screening Approach for Identifying Compounds That Inhibit Nonhomologous End Joining 2018
    2018 MRI Is a DNA Damage Response Adaptor during Classical Non-homologous End JoiningMolecular Cell.  71:332-342.e8. 2018
    2018 The histone chaperone ASF1 regulates the activation of ATM and DNA-PKcs in response to DNA double-strand breaksCell Cycle.  17:1413-1424. 2018
    2018 The Histone Chaperones ASF1 and CAF-1 Promote MMS22L-TONSL-Mediated Rad51 Loading onto ssDNA during Homologous Recombination in Human CellsMolecular Cell.  69:879-892.e5. 2018
    2018 Corrected and republished from: BCL11A is a critical component of a transcriptional network that activates RAG expression and V(D)J recombinationMolecular and Cellular Biology.  38. 2018
    2017 Retraction: "The BCL11A transcription factor directly activates RAG gene expression and V(D)J recombination." [Molecular and Cellular Biology, 33, 9, (2013), (1768-1781)] doi: 10.1128/MCB.00987-12Molecular and Cellular Biology.  37. 2017
    2017 A type I IFN-dependent DNA damage response regulates the genetic program and inflammasome activation in macrophageseLife.  6. 2017
    2017 Deficiency of XLF and PAXX prevents DNA double-strand break repair by non-homologous end joining in lymphocytesCell Cycle.  16:286-295. 2017
    2016 DNA Breaks and End Resection Measured Genome-wide by End SequencingMolecular Cell.  63:898-911. 2016
    2016 Modeling altered T-cell development with induced pluripotent stem cells from patients with RAG1-dependent immune deficienciesBlood.  128:783-793. 2016
    2016 Unique epigenetic influence of H2AX phosphorylation and H3K56 acetylation on normal stem cell radioresponses 2016
    2016 RAG-mediated DNA double-strand breaks activate a cell type-specific checkpoint to inhibit pre-B cell receptor signalsJournal of Experimental Medicine.  213:209-223. 2016
    2016 A novel secreted protein, MYR1, is central to Toxoplasma’s manipulation of host cellsmBio.  7. 2016
    2015 DNA damage responses: Beyond double-strand break repairCurrent Biology.  25:R45-R46. 2015
    2015 Functional analysis of naturally occurring DCLRE1C mutations and correlation with the clinical phenotype of ARTEMIS deficiencyJournal of Allergy and Clinical Immunology.  136:140-150.e7. 2015
    2014 ATM deficiency: Revealing the pathways to cancerCell Cycle.  13:2992. 2014
    2014 KAP-1 promotes resection of broken DNA ends not protected by γ-H2AX and 53BP1 in G₁-phase lymphocytes.Molecular and Cellular Biology.  34:2811-2821. 2014
    2014 Catalytic and Noncatalytic Roles of the CtIP Endonuclease in Double-Strand Break End ResectionMolecular Cell.  54:1022-1033. 2014
    2014 Posttranscriptional regulation of c-Myc expression in adult murine HSCs during homeostasis and interferon-α-induced stress responseBlood.  123:3909-3913. 2014
    2014 β-Catenin induces T-cell transformation by promoting genomic instability 2014
    2014 HCoDES Reveals Chromosomal DNA End Structures with Single-Nucleotide ResolutionMolecular Cell.  56:808-818. 2014
    2014 L-Myc expression by dendritic cells is required for optimal T-cell primingNature.  507:243-247. 2014
    2013 Functional intersection of ATM and DNA-dependent protein kinase catalytic subunit in coding end joining during V(D)J recombinationMolecular and Cellular Biology.  33:3568-3579. 2013
    2013 Metabolic sensor AMPK directly phosphorylates RAG1 protein and regulates V(D)J recombination 2013
    2013 53BP1 mediates productive and mutagenic DNA repair through distinct phosphoprotein interactionsCell.  153:1266-1280. 2013
    2013 Cutting Edge: Cell-autonomous control of IL-7 response revealed in a novel stage of precursor B cellsJournal of Immunology.  190:2485-2489. 2013
    2013 DNA damage activates a complex transcriptional response in murine lymphocytes that includes both physiological and cancer-predisposition programsBMC Genomics.  14. 2013
    2013 The Ataxia telangiectasia mutated kinase controls Igκ allelic exclusion by inhibiting secondary Vκ-to-Jκ rearrangementsJournal of Experimental Medicine.  210:233-239. 2013
    2013 The bcl11a transcription factor directly activates RAG gene expression and V(D)J recombinationMolecular and Cellular Biology.  33:1768-1781. 2013
    2012 Integrated signaling in developing lymphocytes: The role of DNA damage responsesCell Cycle.  11:4129-4134. 2012
    2012 The cell-cycle regulator c-Myc is essential for the formation and maintenance of germinal centersNature Immunology.  13:1092-1100. 2012
    2012 Loss of ATM kinase activity leads to embryonic lethality in mice 2012
    2012 Redundant and nonredundant functions of ATM and H2AX in αβ T-lineage lymphocytesJournal of Immunology.  189:1372-1379. 2012
    2012 The response to and repair of RAG-mediated DNA double-strand breaksAnnual Review of Immunology.  30:175-202. 2012
    2012 Lymphocyte Development: Integration of DNA Damage Response SignalingAdvances in Immunology.  116:175-204. 2012
    2012 Preparing targets for V(D)J recombinase: Transcription paves the wayJournal of Immunology.  188:7-9. 2012
    2012 RAG-induced DNA double-strand breaks signal through Pim2 to promote pre-B cell survival and limit proliferationJournal of Experimental Medicine.  209:11-17. 2012
    2011 Regulation of TCRβ allelic exclusion by gene segment proximity and accessibilityJournal of Immunology.  187:6374-6381. 2011
    2011 Repair of chromosomal RAG-mediated DNA breaks by mutant RAG proteins lacking phosphatidylinositol 3-like kinase consensus phosphorylation sitesJournal of Immunology.  187:1826-1834. 2011
    2011 Out-of-frame T cell receptor beta transcripts are eliminated by multiple pathways In VivoPLoS ONE.  6. 2011
    2011 Unique and redundant functions of ATM and DNA-PKcs during V(D)J recombinationCell Cycle.  10:1928-1935. 2011
    2011 Congenital bone marrow failure in DNA-PKcs mutant mice associated with deficiencies in DNA repair 2011
    2011 H2AX prevents CtIP-mediated DNA end resection and aberrant repair in G1-phase lymphocytes (Nature 469 (2010) (245-249))Nature.  472:247. 2011
    2011 Ataxia telangiectasia mutated (Atm) and DNA-PKcs kinases have overlapping activities during chromosomal signal joint formation. 2011
    2011 H2AX prevents CtIP-mediated DNA end resection and aberrant repair in G1-phase lymphocytesNature.  469:245-250. 2011
    2010 Erratum: RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning of immunoglobulin loci (Nature Immunology (2009) 10 (655-664))Nature Immunology.  11:356. 2010
    2010 Erratum: RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning of immunoglobulin loci (Nature Immunology (2009) 10 (655-664))Nature Immunology.  11:355-356. 2010
    2010 Regulation of hematopoietic stem cell differentiation by a single ubiquitin ligase-substrate complexNature Immunology.  11:207-215. 2010
    2009 Aberrantly resolved RAG-mediated DNA breaks in Atm-deficient lymphocytes target chromosomal breakpoints in cis 2009
    2009 Histone H2AX stabilizes broken DNA strands to suppress chromosome breaks and translocations during V(D)J recombinationJournal of Experimental Medicine.  206:2625-2639. 2009
    2009 Erratum: RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning of immunoglobulin loci (Nature Immunology (2009) vol. 10 (655-664))Nature Immunology.  10:1034. 2009
    2009 Novel roles for A-type lamins in telomere biology and the DNA damage response pathway 2009
    2009 Chimeric IgH-TCR/ translocations in T lymphocytes mediated by RAGCell Cycle.  8:2408-2412. 2009
    2009 Intrathymic proliferation wave essential for Vα14+ natural killer T cell development depends on c-Myc 2009
    2009 RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning of immunoglobulin lociNature Immunology.  10:655-664. 2009
    2009 Formation of Dynamic γ-H2AX Domains along Broken DNA Strands Is Distinctly Regulated by ATM and MDC1 and Dependent upon H2AX Densities in ChromatinMolecular Cell.  34:298-310. 2009
    2009 MRN complex function in the repair of chromosomal Rag-mediated DNA double-strand breaksJournal of Experimental Medicine.  206:669-679. 2009
    2009 Functional overlap in the cis-acting regulation of the V(D)J recombination at the TCRβ locusMolecular Immunology.  46:321-326. 2009
    2008 Collateral Damage from Antigen Receptor Gene DiversificationCell.  135:1009-1012. 2008
    2008 DNA double-strand breaks activate a multi-functional genetic program in developing lymphocytesNature.  456:819-824. 2008
    2008 53BP1 facilitates long-range DNA end-joining during V(D)J recombinationNature.  456:529-533. 2008
    2008 A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cellsNature.  456:259-263. 2008
    2008 Aberrant V(D)J recombination in ataxia telangiectasia mutated-deficient lymphocytes is dependent on nonhomologous DNA end joiningJournal of Immunology.  181:2620-2625. 2008
    2008 Dynamic regulation of c-Myc proto-oncogene expression during lymphocyte development revealed by a GFP-c-Myc knock-in mouseEuropean Journal of Immunology.  38:342-349. 2008
    2007 SWI-SNF: Promoter of accessibilityNature Immunology.  8:795-796. 2007
    2007 ATM Prevents the Persistence and Propagation of Chromosome Breaks in LymphocytesCell.  130:63-75. 2007
    2007 Developmental stage-specific regulation of TCR-α-chain gene assembly by intrinsic features of the TEA promoterJournal of Immunology.  179:449-454. 2007
    2007 γ-Herpesvirus Kinase Actively Initiates a DNA Damage Response by Inducing Phosphorylation of H2AX to Foster Viral ReplicationCell Host and Microbe.  1:275-286. 2007
    2007 Defects in coding joint formation in vivo in developing ATM-deficient B and T lymphocytesJournal of Experimental Medicine.  204:1371-1381. 2007
    2006 Autoreactive marginal zone B cells are spontaneously activated but lymph node B cells require T cell helpJournal of Experimental Medicine.  203:1985-1998. 2006
    2006 ATM stabilizes DNA double-strand-break complexes during V(D)J recombinationNature.  442:466-470. 2006
    2006 Selective requirement of p38α MAPK in cytokine-dependent, but not antigen receptor-dependent, Th1 responsesJournal of Immunology.  176:4616-4621. 2006
    2006 Proteasome activator PA200 is required for normal spermatogenesisMolecular and Cellular Biology.  26:2999-3007. 2006
    2005 Revision of T cell receptor α chain genes is required for normal T lymphocyte development 2005
    2005 Lymphocyte antigen receptor gene assembly: Multiple layers of regulationImmunologic Research.  32:253-258. 2005
    2005 Chromosomal excision of TCRδ chain genes is dispensable for αβ T cell lineage commitmentInternational Immunology.  17:225-232. 2005
    2005 Intra- and inter-allelic ordering of T cell receptor β chain gene assemblyEuropean Journal of Immunology.  35:964-970. 2005
    2005 MAPK p38α is dispensable for lymphocyte development and proliferationJournal of Immunology.  174:1239-1244. 2005
    2005 Regulation of T cell receptor β allelic exclusion at a level beyond accessibilityNature Immunology.  6:189-197. 2005
    2004 Regulation of T-cell receptor β-chain gene assembly by recombination signals: The beyond 12/23 restrictionImmunological Reviews.  200:36-43. 2004
    2003 The B12/23 Restriction Is Critically Dependent on Recombination Signal Nonamer and Spacer SequencesJournal of Immunology.  171:6604-6610. 2003
    2003 T-cell glucocorticoid receptor is required to suppress COX-2-mediated lethal immune activationNature Medicine.  9:1318-1322. 2003
    2003 T cell receptor CDR3 loop length repertoire is determined primarily by features of the V(D)J recombination reactionEuropean Journal of Immunology.  33:1568-1575. 2003
    2003 T cell receptor (TCR) α/δ locus enhancer identity and position are critical for the assembly of TCR δ and a variable region genes 2003
    2003 Cutting edge: Targeting of Vβ to Dβ rearrangement by RSSs can be mediated by the V(D)J recombinase in the absence of additional lymphoid-specific factorsJournal of Immunology.  170:5-9. 2003
    2002 Analysis of the complex genomic structure of Bcl-x and its relationship to Bcl-xγ expression after CD28-dependent costimulationMolecular Immunology.  39:45-55. 2002
    2002 Thymocyte apoptosis induced by T cell activation is mediated by glucocorticoids in vivoJournal of Immunology.  169:1837-1843. 2002
    2002 Green fluorescent protein-glucocorticoid receptor knockin mice reveal dynamic receptor modulation during thymocyte developmentJournal of Immunology.  169:1309-1318. 2002
    2002 T cell costimulation through CD28 depends on induction of the Bcl-xγ isoform: Analysis of Bcl-xγ-deficient miceJournal of Experimental Medicine.  196:87-95. 2002
    2002 Allelic exclusion at the TCRβ locusCurrent Opinion in Immunology.  14:230-234. 2002
    2002 Restrictions limiting the generation of DNA double strand breaks during chromosomal V(D)J recombinationJournal of Experimental Medicine.  195:309-316. 2002
    2002 Distinct effects of T-bet in Th1 lineage commitment and IFN-γ production in CD4 and CD8 T cellsScience.  295:338-342. 2002
    2002 Knock-ins and conditional knockouts: In vivo analysis of glucocorticoid receptor regulation and functionEndocrine Research.  28:545-551. 2002
    2001 Assessing a role for enhancer-blocking activity in gene regulation within the murine T-cell receptor α/δ locusImmunology.  104:11-18. 2001
    2000 Mechanisms that direct ordered assembly of T cell receptor β locus V, D, and J gene segments 2000
    2000 Cloning and functional characterization of the early-lymphocyte-specific Pb99 geneMolecular and Cellular Biology.  20:4405-4410. 2000
    2000 Recombination signal sequences restrict chromosomal V(D)J recombination beyond the 12/23 ruleNature.  405:583-586. 2000
    1999 Requirement for B cell linker protein (BLNK) in B cell developmentScience.  286:1949-1954. 1999
    1999 Host-parasite relationships between Echinostoma caproni and RAG-2- deficient mice 1999
    1999 Recombination and transcription of the endogenous Ig heavy chain locus is effected by the Ig heavy chain intronic enhancer core region in the absence of the matrix attachment regions 1999
    1999 A developmental switch from TCRδ enhancer to TCRα enhancer function during thymocyte maturationImmunity.  10:723-733. 1999
    1999 Developmental regulation of TCRδ locus accessibility and expression by the TCRδ enhancerImmunity.  10:503-513. 1999
    1999 Immature thymocytes employ distinct signaling pathways for allelic exclusion versus differentiation and expansionImmunity.  10:537-546. 1999
    1998 Assembly of productive T cell receptor δ variable region genes exhibits allelic inclusionJournal of Experimental Medicine.  188:1465-1471. 1998
    1998 Accessibility control of variable region gene assembly during T-cell developmentImmunological Reviews.  165:121-130. 1998
    1997 Function of the TCRα enhancer in αβ and γδ T cellsImmunity.  7:505-515. 1997
    1996 Accessibility control of antigen-receptor variable-region gene assembly: Role of cis-acting elementsAnnual Review of Immunology.  14:459-481. 1996
    1992 Disruption of the CD4-p56(lck) complex is required for rapid internalization of CD4 1992
    1991 Glycolipid-anchored form of CD4 increases intercellular adhesion but is unable to enhance T cell activationJournal of Immunology.  147:428-431. 1991
    1990 Human immunodeficiency virus infection is efficiently mediated by a glycolipid-anchored form of CD4 1990
    1990 The cytoplasmic domain of CD4 is required for stable association with the lymphocyte‐specific tyrosine protein kinase p56lckEuropean Journal of Immunology.  20:1397-1400. 1990
    1989 Requirements for modulation of the CD4 molecule in response to phorbol myristate acetate. Role of the cytoplasmic domainJournal of Immunology.  142:1457-1462. 1989
    1989 The biologic roles of CD2, CD4, and CD8 in T-cell activation.Annual Review of Immunology.  7:579-599. 1989
    1988 Expression and function of CD4 in a murine T-cell hybridomaNature.  328:351-353. 1988
    1988 Inhibition of CD4+ T cell function by the HIV envelope protein, gp120Journal of Immunology.  141:3715-3717. 1988
    1988 Functional Analysis of Cd2, cd4, and cd8 in t‐Cell ActivationAnnals of the New York Academy of Sciences.  532:199-206. 1988
    1988 Functional analysis of a cytoplasmic domain-deleted mutant of the CD4 moleculeJournal of Immunology.  141:49-54. 1988
    1986 Cutaneous acute graft-versus-host disease to minor histocompatibility antigens in a murine model: Histologic analysis and correlation to clinical diseaseJournal of Investigative Dermatology.  86:371-375. 1986
    1983 Determination Of Pulegone In H. Pulegioides And Peppermint Oil By Thin Layer Chromatography With Densitometry 1983
    1983 Separation and quantification of epinephrine, norepinephrine, and dopamine by chromatography on diphenyl thin layers 1983
    1982 A Comparison Of Amino Acid Separations On Silica Gel, Cellulose, And Ion Exchange Thin Layers 1982
    1981 Reversed phase thin layer chromatography of phenols on chemically bonded C18 layers 1981

    Research Overview

  • Research in the Sleckman Lab focuses on discovering novel cellular pathways that maintain the fundamental integrity of the mammalian genome through the repair of damaged DNA. The lab is primarily focused on how genomic DNA double-stranded breaks (DSBs) are generated and repaired. These studies are particularly focused on cancer and how the corruption of DSB repair pathways in cancer cells leads to genomic lesions and a genomic evolution that improves cancer cell fitness. It is these pathways that will be important targets for the development of novel cancer therapeutics. The lab is currently employing cell-based, cutting-edge CRISPR-Cas9 screening approaches to identify novel DNA DSB repair pathways and their components. In addition, we develop and utilize mouse models to establish the role of these pathways in maintaining genome stability in normal and cancer cells in vivo. We are currently active in three specific areas:

    1. Identifying pathways that prevent aberrant DNA DSB repair
    2. Normal cellular functions regulated by the DNA damage response
    3. DNA DSB repair and cancer fitness
  • Education And Training

  • Doctor of Medicine in Laboratory Medicine Residency Program, Harvard University 1989
  • Doctor of Philosophy in Immunology, Harvard University 1989
  • Bachelor of Science or Mathematics in Biology, Lafayette College 1983
  • Brigham and Women's Hospital, Residency 1992
  • Harvard Medical School, Postdoctoral Fellowship 1998
  • Dana–Farber Cancer Institute, Postdoctoral Fellowship 1992
  • Full Name

  • Barry Sleckman