个人简介
Dr. Schatz has made fundamental contributions to our understanding of the mechanisms that assemble and diversify antigen receptor genes that encode antibodies and T cell receptors. He is best known for the discovery of RAG1 and RAG2, subsequent biochemical insights into RAG function and evolutionary origins, and the discovery of two distinct levels of regulation of somatic hypermutation.
As a graduate student with David Baltimore, Schatz established an assay for the detection of V(D)J recombination activity and, in collaboration with Marjorie Oettinger, used this assay to isolate the Recombination Activating Genes RAG1 and RAG2, whose gene products constitute the vital, lymphocyte-specific components of the V(D)J recombination machinery. This discovery transformed the field of V(D)J recombination and stands as a seminal event in the field of Immunology. Schatz has since provided important insights into the mechanism of V(D)J recombination. Schatz and Martin Gellert co-discovered the ability of RAG1/2 to perform DNA transposition, with implications for our understanding of the evolution of the adaptive immune system and the mechanism of V(D)J recombination. Schatz has made important contributions to the field of somatic hypermutation, including the discovery of strand asymmetric spreading of mutations and the existence of two distinct levels of targeting of the reaction, one of which relies on gene-specific DNA repair: error-prone at immunoglobulin genes and high-fidelity at numerous proto-oncogenes. His laboratory remains interested in understanding the mechanism of regulation of V(D)J recombination and somatic hypermutation.
Schatz has co-authored over 110 articles, many in prestigious journals, and has been the recipient of numerous prizes and awards, including the Rhodes Scholarship, the Snow Prize (Yale University's top award to a graduating senior), the National Science Foundation Presidential Faculty Fellows Award, and the American Association of Immunologists-BD Biosciences Investigator Award. He has been active as an editor and reviewer, serving as Co-Editor of the journal Immunity, as a member of the editorial board of a number of journals, and as a member and Chair of the NIH study section Cellular and Molecular Immunology-A. Schatz has also been very interested in graduate education, serving for many years as the Director of Graduate Studies and Graduate Admissions for Immunobiology and as a member of the Executive Committee of the Biological and Biomedical Sciences (BBS) Program.
Schatz received B.S. and M.S. degrees in Molecular Biophysics and Biochemistry from Yale University in 1980, and a M.A. degree in Philosophy and Politics from Oxford University in 1982. His Ph.D. degree (1990) and postdoctoral training were done with Dr. David Baltimore at the Massachusetts Institute of Technology and the Whitehead Institute for Biomedical Research.
PhD Massachusetts Institute of Technology (1990)
Postdoctoral Fellow Whitehead Institute and MIT
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Discovery of an Active RAG Transposon Illuminates the Origins of V(D)J Recombination
Huang, S., Tao, X., Yuan, S., Zhang, Y., Li, P., Beilinson, H.A., Zhang, Y., Yu, W., Pontarotti, P., Escriva, H., Le Petillon, Y., Liu, X., Chen, S., Schatz, D.G., and Xu, A. (2016). Cell 166, 102-114.
Collaboration of RAG2 with RAG1-like proteins during the evolution of V(D)J recombination
Carmona, L.M., Fugmann, S.D., and Schatz, D.G. (2016). Genes Dev 30, 909-917.
RAG Represents a Widespread Threat to the Lymphocyte Genome.
Teng, G., Maman, Y., Resch, W., Kim, M., Yamane, A., Qian, J., Kieffer-Kwon, K.R., Mandal, M., Ji, Y., Meffre, E., Clark, M.R., Cowell, L.G., Casellas, R., and Schatz, D.G. (2015). Cell 162, 751-765.
Targeting of somatic hypermutation by immunoglobulin enhancer and enhancer-like sequences.
Buerstedde, J.M., Alinikula, J., Arakawa, H., McDonald, J.J., and Schatz, D.G. (2014). Targeting of somatic hypermutation by immunoglobulin enhancer and enhancer-like sequences. PLoS Biol 12, e1001831.
The in vivo pattern of binding of RAG1 and RAG2 to antigen receptor loci
Ji, Y., Resch, W., Corbett, E., Yamane, A., Casellas, R., and Schatz, D.G. (2010). The in vivo pattern of binding of RAG1 and RAG2 to antigen receptor loci. Cell 141, 419-431.
Two levels of protection for the B cell genome during somatic hypermutation.
Liu, M., Duke, J. L., Richter, D. J., Vinuesa, C. G., Goodnow, C. C., Kleinstein, S. H. and Schatz, D. G. Two levels of protection for the B cell genome during somatic hypermutation. Nature 451, 841-845 (2008)
Fisher MR, Rivera-Reyes A, Bloch NB, Schatz DG, Bassing CH: Immature Lymphocytes Inhibit Rag1 and Rag2 Transcription and V(D)J Recombination in Response to DNA Double-Strand Breaks. J Immunol. 2017 Apr 1; 2017 Feb 17. PMID: 28213501
Carmona LM, Schatz DG: New insights into the evolutionary origins of the recombination-activating gene proteins and V(D)J recombination. FEBS J. 2016 Dec 14; 2016 Dec 14. PMID: 27973733
Maman Y, Teng G, Seth R, Kleinstein SH, Schatz DG: RAG1 targeting in the genome is dominated by chromatin interactions mediated by the non-core regions of RAG1 and RAG2. Nucleic Acids Res. 2016 Nov 16; 2016 Jul 19. PMID: 27436288
Brauer PM, Pessach IM, Clarke E, Rowe JH, Ott de Bruin L, Lee YN, Dominguez-Brauer C, Comeau AM, Awong G, Felgentreff K, Zhang YH, Bredemeyer A, Al-Herz W, Du L, Ververs F, Kennedy M, Giliani S, Keller G, Sleckman BP, Schatz DG, Bushman FD, Notarangelo LD, Zúñiga-Pflücker JC: Modeling altered T-cell development with induced pluripotent stem cells from patients with RAG1-dependent immune deficiencies. Blood. 2016 Aug 11; 2016 Jun 14. PMID: 27301863
Huang S, Tao X, Yuan S, Zhang Y, Li P, Beilinson HA, Zhang Y, Yu W, Pontarotti P, Escriva H, Le Petillon Y, Liu X, Chen S, Schatz DG, Xu A: Discovery of an Active RAG Transposon Illuminates the Origins of V(D)J Recombination. Cell. 2016 Jun 30; 2016 Jun 9. PMID: 27293192
Carmona LM, Fugmann SD, Schatz DG: Collaboration of RAG2 with RAG1-like proteins during the evolution of V(D)J recombination. Genes Dev. 2016 Apr 15; 2016 Apr 7. PMID: 27056670
Williams AM, Maman Y, Alinikula J, Schatz DG: Bcl6 Is Required for Somatic Hypermutation and Gene Conversion in Chicken DT40 Cells. PLoS One. 2016; 2016 Feb 22. PMID: 26900682
Hu J, Zhang Y, Zhao L, Frock RL, Du Z, Meyers RM, Meng FL, Schatz DG, Alt FW: Chromosomal Loop Domains Direct the Recombination of Antigen Receptor Genes. Cell. 2015 Nov 5; 2015 Oct 22. PMID: 26593423
Shetty K, Schatz DG: Recruitment of RAG1 and RAG2 to Chromatinized DNA during V(D)J Recombination. Mol Cell Biol. 2015 Nov; 2015 Aug 24. PMID: 26303526
Mandal M, Hamel KM, Maienschein-Cline M, Tanaka A, Teng G, Tuteja JH, Bunker JJ, Bahroos N, Eppig JJ, Schatz DG, Clark MR: Histone reader BRWD1 targets and restricts recombination to the Igk locus. Nat Immunol. 2015 Oct; 2015 Aug 24. PMID: 26301565
Choi J, Goh G, Walradt T, Hong BS, Bunick CG, Chen K, Bjornson RD, Maman Y, Wang T, Tordoff J, Carlson K, Overton JD, Liu KJ, Lewis JM, Devine L, Barbarotta L, Foss FM, Subtil A, Vonderheid EC, Edelson RL, Schatz DG, Boggon TJ, Girardi M, Lifton RP: Genomic landscape of cutaneous T cell lymphoma. Nat Genet. 2015 Sep; 2015 Jul 20. PMID: 26192916
Teng G, Maman Y, Resch W, Kim M, Yamane A, Qian J, Kieffer-Kwon KR, Mandal M, Ji Y, Meffre E, Clark MR, Cowell LG, Casellas R, Schatz DG: RAG Represents a Widespread Threat to the Lymphocyte Genome. Cell. 2015 Aug 13; 2015 Jul 30. PMID: 26234156
Swaminathan S, Klemm L, Park E, Papaemmanuil E, Ford A, Kweon SM, Trageser D, Hasselfeld B, Henke N, Mooster J, Geng H, Schwarz K, Kogan SC, Casellas R, Schatz DG, Lieber MR, Greaves MF, Müschen M: Mechanisms of clonal evolution in childhood acute lymphoblastic leukemia. Nat Immunol. 2015 Jul; 2015 May 18. PMID: 25985233
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