Jeffrey L. Sklar MD

Professor of Pathology and of Laboratory Medicine; Director, Molecular Diagnostics Research Program


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.

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.