Jeffrey L. Sklar MD, PhD

Professor of Pathology and of Laboratory Medicine; Director, Molecular Diagnostics Program; Director, Molecular Genetics Pathology Fellowship; Director, Molecular Tumor Profiling Laboratory; Director of Molecular and Genomic Pathology

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Departments & Organizations

Biological and Biomedical Sciences (BBS): Molecular Medicine, Pharmacology, and Physiology

Yale Medical Group

Cancer Center, Yale: Hematology Program

Vascular Biology and Therapeutics Program

Pathology: Autopsy | Surgical Pathology | Molecular Diagnostics | Pathology Research

Laboratory Medicine: Molecular Diagnostics

Gene Regulation and Functional Genomics

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Biography

B.A. (Biology) Haverford College
M.D. School of Medicine, Yale University
Ph.D. Molecular Biophysics/Biochemistry, Yale University
Residency, Pathology, Stanford University Medical Center
Post-doctoral Fellowship (Biochemistry), Stanford University

Assistant Professor to Associate Professor of Pathology, Stanford University Sch of Med, 1981-89
Associate Professor to Professor of Pathology, Harvard Medical School, 1989-2003
Professor of Pathology and Laboratory Medicine, Yale University Sch of Med, 2003-

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 discoverd 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.

Selected publications:

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.

Li H, Ma X, Wang J, Koontz J, Nucci M, Sklar J. Effects of rearrangement and allelic exclusion of JJAZ1/SUZ12 on cell proliferation and survival. Proc Natl Acad Sci USA 2007; 104: 20001-20006.

Li H, Wang J, Mor G, Sklar J. A neoplastic gene fusion mimics trans-splicing of RNAs in normal cells. Science 2008; 321: 1357-1361.