Sklar, Jeffrey L - Yale University - Biological & Biomedical Sciences

个人简介

Jeffrey Sklar, M.D., Ph.D., received a B.A. in Biology from Haverford College, an M.D. from Yale School of Medicine, and a Ph.D. in Molecular Biophysics/Biochemistry from Yale University. He completed his residency in pathology at Stanford University Medical Center and his post-doctoral fellowship (in Biochemistry) at Stanford University. He served as Assistant Professor and then Associate Professor of Pathology with tenure at Stanford University School of Medicine, 1981-89; then as Associate Professor and then Professor of Pathology at Harvard Medical School, 1989-2003. Currently, he is Professor of Pathology and Laboratory Medicine at Yale School of Medicine (2003-present). Clinical interests: Molecular diagnostics. Research Interests: Molecular biology of human disease, especially cancer; gene regulation; chromosome structure and chromosomal aberrations in human disease; trans-splicing of RNA; genetic predisposition to type 2 diabetes; immunogenetics. The lab is presently particularly interested in two genes, JAZF1 and JJAZ1/SUZ12, which we discovered to be fused in the cells of certain uterine tumors. JJAZ1 is a Polycomb group gene, the product of which is essential for histone methylations that regulate chromatin remodeling and activity. We have investigated how the JAZF1-JJAZ1 fusion functions in oncogenesis and found that its action has features not previously described in cancer. Recently, we discovered that JAZF1-JJAZ1 RNA is produced by hormonally regulated trans-splicing between the pre-mRNAs for the two genes in normal endometrium. This discovery has led us to explore other examples of recombination between RNAs, which is much more common than previously thought. Relative to JJAZ1, little is known about the function of JAZF1, although single nucleotide polymorphisms in this gene are associated with altered risk for type 2 diabetes and prostate cancer. We are currently investigating the mechanisms of these associations. PhD Yale University (1977) MD Yale University School of Medicine (1977) Resident Stanford University School of Medicine Fellow Stanford University School of Medicine

研究领域

Chromosomes; Genetics; Immunogenetics; Neoplasms by Site; Pathology; Medical Laboratory Science; Diagnostic Techniques and Procedures; Molecular Diagnostic Techniques

近期论文

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Effects of rearrangement and allelic exclusion of JJAZ1/SUZ12 on cell proliferation and survival Li H, Ma X, Wang J, Koontz J, Nucci M, Sklar J. (2007). Effects of rearrangement and allelic exclusion of JJAZ1/SUZ12 on cell proliferation and survival. Proc Natl Acad Sci USA. 104: 20001-20006. A neoplastic gene fusion mimics trans-splicing of RNAs in normal cells Li H, Wang J, Mor G, Sklar J. A neoplastic gene fusion mimics trans-splicing of RNAs in normal cells. Science, in press. Immunoglobulin gene rearrangement as a diagnostic criterion of B cell lymphoma Cleary ML, Chao J, Warnke R, Sklar J. Immunoglobulin gene rearrangement as a diagnostic criterion of B cell lymphoma. Proc Natl Acad Sci USA 1984 81:593-597. Clonal rearrangements of T cell receptor genes in mycosis fungoides and dermatopathic lymphadenopathy Weiss LM, Hu E, Wood GS, Moulds C, Cleary ML, Warnke R, Sklar J. Clonal rearrangements of T cell receptor genes in mycosis fungoides and dermatopathic lymphadenopathy. New Engl J Med 1985 313:537-544. Detection of Epstein-Barr viral DNA in Reed-Sternberg cells of Hodgkin's disease Weiss LM, Movahed LA, Warnke RA, Sklar J. Detection of Epstein-Barr viral DNA in Reed-Sternberg cells of Hodgkin's disease. New Engl J Med 1989 320:502-506. T-cell receptor gene trans-rearrangements: Chimeric gamma-delta genes in normal lymphoid tissues Tycko B, Palmer JD, Sklar J. T-cell receptor gene trans-rearrangements: Chimeric gamma-delta genes in normal lymphoid tissues. Science 1989 245:1242-1246. TAN-1, the human homolog of the Drosophila Notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms Ellisen LW, Bird J, West DC, Soreng AL, Reynolds TC, Smith SD, Sklar J. TAN-1, the human homolog of the Drosophila Notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell 1991 66:649-661. Frequent fusion of the JAZF1 and JJAZ1 genes in endometrial stromal tumors Koontz JI, Soreng AL, Nucci M, Kuo FC, Pauwels P, van den Berghe H, Dal Cin P, Fletcher JA, Sklar J. Frequent fusion of the JAZF1 and JJAZ1 genes in endometrial stromal tumors. Proc Natl Acad of Sci USA 2001 98: 6348-6353. Lih CJ, Harrington RD, Sims DJ, Harper KN, Bouk CH, Datta V, Yau J, Singh RR, Routbort MJ, Luthra R, Patel KP, Mantha GS, Krishnamurthy S, Ronski K, Walther Z, Finberg KE, Canosa S, Robinson H, Raymond A, Le LP, McShane LM, Polley EC, Conley BA, Doroshow JH, Iafrate AJ, Sklar JL, Hamilton SR, Williams PM: Analytical Validation of the Next-Generation Sequencing Assay for a Nationwide Signal-Finding Clinical Trial: Molecular Analysis for Therapy Choice Clinical Trial. J Mol Diagn. 2017 Mar; 2017 Feb 7. PMID: 28188106 Ma X, Wang J, Wang J, Ma CX, Gao X, Patriub V, Sklar JL: The JAZF1-SUZ12 fusion protein disrupts PRC2 complexes and impairs chromatin repression during human endometrial stromal tumorogenesis. Oncotarget. 2017 Jan 17. PMID: 27845897