Faculty and Staff
Nutritional and Metabolic Doctoral Training Faculty
Debra J. Wolgemuth, PhD
Professor of Genetics and Development
Professor of Obstetrics and Gynecology
Director, Nutritional and Metabolic Biology PhD program
Associate Director for Research, Institute of Human Nutrition
B.A. - 1969, Gettysburg College
M.A. - 1971, Vanderbilt University
Ph.D. - 1978, Columbia University
Genetic control of mammalian germ cell differentiation
The research interests of the Wolgemuth lab focus on understanding the genetic control of gametogenesis and embryogenesis using mouse models and gene targeting, transgenic, and molecular and cell biological approaches. The first of the three major projects involves understanding the function of the A and E-type cyclins during the mitotic and meiotic cell cycles mainly during spermatogenesis but also in oogenesis. We have demonstrated that cyclin A1 is essential for the progression of spermatocytes into the first meiotic division, that cyclin A2 is required for mitotic divisions of male germ cell stem cells, and that the E-type cyclins have unexpected function during meiosis, notably in the maintenance of telomere integrity. A second area of research involves elucidating the function of the BET family of double bromodomain-containing proteins, proteins that read epigenetic marks, during germ cell differentiation and neural development. We showed that the BET family member BRDT is essential for proper chromatin remodeling and transcriptional regulation during meiotic prophase and again during spermiogenesis and that BRD2 is essential for embryonic survival and neural differentiation and function, in particular in the etiology of seizure susceptibility. We have recently generated a conditional knockout model of Brd2 which will allow determining its function in adult tissues, including the germ line. Finally, the lab is pursuing studies on the role of retinoid signaling during male germ cell differentiation, again in using molecular genetic approaches in the mouse model, and more recently, pharmacologic intervention. We have used a pan-antagonist of the retinoic acid receptors (RARs) to disrupt spermatogenesis and induce sterility, importantly in a reversible manner. Long-term efforts in this project will involve developing RAR-alpha specific antagonists, identifying the target genes of RAR-alpha, and discerning their function in germ cell-Sertoli cell interactions.
Selected Publications - Pubmed
Liu, D., M.M. Matzuk, W.K. Sung, Q. Guo, P. Wang and D.J. Wolgemuth. (1998). Cyclin A1 is required for meiosis in the male mouse. Nat. Genet. 20, 377-380. [No PMCID; PMID: 9843212].
Shang, E., H.D. Nickerson, D. Wen, X. Wang and D.J. Wolgemuth. (2007). The first bromodomain of Brdt, a testis-specific member of the BET sub-family of double-bromodomain-containing proteins, is essential for male germ cell differentiation. Development. 134, 3507-3515. [No PMCID; PMID: 17728347]
Shang, E., X. Wang, D. Wen, D.A. Greenberg and D.J. Wolgemuth. (2009). Double bromodomain-containing gene Brd2 is essential for embryonic development in mouse. Dev. Dyn. 238, 908-917. [PMCID: 2771124; PMID: 19301389].
Chung, S.S., X. Wang, S.S. Roberts, S.M. Griffey, P.R. Reczek and D.J. Wolgemuth. (2011). Oral administration of a retinoic Acid receptor antagonist reversibly inhibits spermatogenesis in mice. Endocrinology. 152, 2492-2502. [PMCID: 3100616; PMID: 21505053].
Our studies were highlighted as a feature article in Endocrine News, the official newsletter of the Endocrine Society and have been the subject of attention in the public media world-wide (since June, 2011). The work was also highlighted in a leading edge previews article in Cell (Bremner WJ Cell, 150, 1-2, 2012) and in a news focus article in Science 338, 318-320 (2012).
Berkovits, B.D., L. Wang, P. Guarnieri and D.J. Wolgemuth. (2012). The testis-specific double bromodomain-containing protein BRDT forms a complex with multiple spliceosome components and is required for mRNA splicing and 3'-UTR truncation in round spermatids. Nucleic Acids Res. 40, 7162-7175. [PMCID: 3424537; PMID: 22570411].
Martinerie, L., M. Manterola, S.S. Chung, S.K. Panigrahi, M. Weisbach, A. Vasileva, Y. Geng, P. Sicinski and D.J. Wolgemuth. (2014). Mammalian E-type cyclins control chromosome pairing, telomere stability and CDK2 localization in male meiosis. PLoS Genet. 10, e1004165. [PMCID: 3937215; PMID: 24586195].
Complete List of Published Work in MyBibliography: