Debra J. Wolgemuth, PhD

Profile Headshot

Overview

Academic Appointments

  • Professor of Genetics & Development

Administrative Titles

  • Associate Director for Research, Institute of Human Nutrition
  • Director, Nutrition and Metabolic Biology PhD Program

Credentials & Experience

Education & Training

  • PhD, Human Genetics and Development , Columbia University
  • Fellowship: Rockefeller University
  • Fellowship: Sloan-Kettering Institute for Cancer Research

Honors & Awards

Damon Runyon-Walter Winchell Cancer Fund Post-doctoral Fellowship
American Cancer Society Post-doctoral Fellowship--declined
Irma T. Hirschl Research Career Development Award
Distinguished Speakers Symposium, American Society for Human Genetics
International Human Frontiers of Science Program
Distinguished Alumna Award, Gettysburg College
Mayent Rothschild Visiting Scholar, Institut Curie, Paris
Board of Trustees, Gettysburg College, Gettysburg, PA
Bohan Visiting Professor, University of Kansas  

Research

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 also 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 us to determine 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 of this project will involve developing RAR-alpha selective antagonists, identifying the target genes of RAR-alpha, and determining their function in germ cell-Sertoli cell interactions.

Research Interests

  • Contraceptive Development
  • Development and Behavioral Research

Grants

RETINOID RECEPTOR ANTAGONISTS AS NOVEL MALE CONTRACEPTIVES (Federal Gov)
Feb 15 2009 - Mar 31 2019

CONTRACEPTIVE DISCOVERY, DEVELOPMENT AND BEHAVIORAL RESEARCH CENTER – PROJECT #1-NOVEL RETINOIC ACID RECEPTOR ALPHA-SELECTIVE ANTAGONISTS (Federal Gov)
Sep 15 2017 - Mar 31 2021

CONTRACEPTIVE DISCOVERY, DEVELOPMENT AND BEHAVIORAL RESEARCH CENTER - PROJECT # 2 (Federal Gov)
Sep 15 2017 - Mar 31 2021

CONTRACEPTIVE DISCOVERY, DEVELOPMENT AND BEHAVIORAL RESEARCH CENTER - PROJECT # 3 (Federal Gov)
Sep 15 2017 - Mar 31 2021

FUNCTION OF THE BROMODOMAIN PROTEIN BRDT IN SPERMATOGENESIS (Federal Gov)
Sep 15 2008 - Jul 31 2018

GRADUATE  TRAINING IN NUTRITION (Federal Gov)
Sep 1 1995 - Aug 31 2020

CONTRACEPTIVE DISCOVERY, DEVELOPMENT AND BEHAVIORAL RESEARCH CENTER - PROJECT # 2 (Federal Gov)

Sep 15 2017 - Mar 31 2021

CONTRACEPTIVE DISCOVERY, DEVELOPMENT AND BEHAVIORAL RESEARCH CENTER - PROJECT # 3 (Federal Gov)

Sep 15 2017 - Mar 31 2021

NOVEL RETINOIC ACID RECEPTOR ALPHASELECTIVE ANTAGONISTS--PROJECT 1 (Federal Gov)

Sep 15 2017 - Mar 31 2021

RETINOID RECEPTOR ANTAGONISTS AS NOVEL MALE CONTRACEPTIVES (Federal Gov)

Feb 15 2009 - Mar 31 2019

FUNCTION OF THE BROMODOMAIN PROTEIN BRDT IN SPERMATOGENESIS (Federal Gov)

Sep 15 2008 - Jul 31 2018

ROLE OF CYCLIN AS IN MAMMALIAN GAMETOGENESIS (Federal Gov)

Sep 1 1997 - Mar 31 2018

INTERDISCIPLINARY TRAINING IN NUTRITIONAL AND POPULATION HEALTH SCIENCES (Federal Gov)

Aug 1 2011 - Jul 31 2017

THE MRAD9 RADIORESISTANCE GENE (Federal Gov)

Dec 1 2000 - Mar 31 2014

FUNCTIONS OF BRDT AND ITS BROMODOMAIN MOTIFS DURING SPERMATO GENESIS (Private)

Aug 1 2011 - Jul 31 2013

MECHANISMS OF GENETIC SEIZURE SUSCEPTIBITLITY IN JUVENLLE MYOCLONIC EPILEPSY (Federal Gov)

Jul 1 2012 - Jun 30 2013

ROLE OF INTRONIC VARIANTS AFFECTING SPLICING IN JUVENILE MYO CLONIC EPILEPSY (Federal Gov)

Sep 30 2009 - Aug 31 2012

MECHANISMS OF GENETIC SEIZURE SUSCEPTIBILITY IN JUVENILE MYOCLONIC EPILEPSY (Federal Gov)

Jul 15 2009 - Jun 30 2012

REGULATION OF CELLULAR CYCLE DURING SPERMATOGENESIS: ROLE OF CYCLIN E IN MALE INFERTILITY (Private)

Nov 1 2010 - Oct 31 2011

Selected Publications

  1. 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].
  2. Liu, D., C. Liao and D.J. Wolgemuth. (2000). A role for cyclin A1 in the activation of MPF and G2-M transition during meiosis of male germ cells in mice. Dev. Biol. 224, 388-400. [No PMCID; PMID: 10926775].
  3. Liao, C., X.Y. Wang, H.Q. Wei, S.Q. Li, T. Merghoub, P.P. Pandolfi and D.J. Wolgemuth. (2001). Altered myelopoiesis and the development of acute myeloid leukemia in transgenic mice overexpressing cyclin A1. Proc. Natl. Acad. Sci. U.S.A. 98, 6853-6858. [PMCID: 34442; PMID: 11381140].
  4. Chung, S.S., W. Sung, X.Y. Wang and D.J. Wolgemuth. (2004). Retinoic acid receptor alpha is required for synchronization of spermatogenic cycles and its absence results in progressive breakdown of the spermatogenic process. Dev. Dyn. 230, 754-766. [PMCID: 3785309; PMID: 15254909].
  5. Chung, S.S., X.Y. Wang and D.J. Wolgemuth. (2005). Male sterility in mice lacking retinoic acid receptor alpha involves specific abnormalities in spermiogenesis. Differentiation. 73, 188-198. [PMCID: 3785313; PMID: 15901285].
  6. Nickerson, H.D., A. Joshi and D.J. Wolgemuth. (2007). Cyclin A1-deficient mice lack histone H3 serine 10 phosphorylation and exhibit altered aurora B dynamics in late prophase of male meiosis. Dev. Biol. 306, 725-735. [PMCID: 2701158; PMID: 17498682].
  7. 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].
  8. 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].
  9. Chung, S.S., X. Wang and D.J. Wolgemuth. (2009). Expression of retinoic acid receptor alpha in the germline is essential for proper cellular association and spermiogenesis during spermatogenesis. Development. 136, 2091-2100. [PMCID: 2685727; PMID: 19465599].
  10. Kalaszczynska, I, Y. Geng, R. Iino, S. Mizuno, Y. Choi, I. Kondratiuk, D.P. Silver, D.J. Wolgemuth, K. Akashi, and P. Sicinski. (2009). Cyclin A is required for proliferation of embryonal and hematopoietic stem cells. Cell. 138, 352-365. [PMCID: PMC2745999; PMID: 19592082].
  11. 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].
  12. Berkovits, B.D. and D.J. Wolgemuth. (2011). The first bromodomain of the testis-specific double bromodomain protein Brdt is required for chromocenter organization that is modulated by genetic background. Dev. Biol. 360, 358-368. [PMCID: 3217133; PMID: 22020252].
  13. 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].
  14. 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].
  15. Chung, S.S.W., X.Y. Wang, D.J. Wolgemuth. (2016) Prolonged oral administration of pan-retinoic acid receptor antagonist inhibits spermatogenesis in mice with a rapid recovery and changes in the expression of influx and efflux transporters. Endocrinology. 157(4), 1601-12. [PMCID: PMC4816726; PMID:26812157].
  16. Wang, L., Wolgemuth, D.J. (2016) BET protein BRDT complexes with HDAC1, PRMT5, and TRIM28 and functions in transcriptional repression during spermatogenesis. J Cell Biochem. 117(6):1429-38. [PMCID: PMC4916496; PMID:26565999].
  17. Manterola, M., Sicinski, P., Wolgemuth,D.J.  (2016). E-type cyclins modulate telomere integrity in mammalian male meiosis. Chromosoma 125, 253-264. [PMCID: PMC4833587; PMID: 26712234].
  18. Manterola, M., T.M. Brown, M. Young Oh, C. Garyn, B.J. Gonzalez, and D.J. Wolgemuth. (2018) BRDT is an essential epigenetic regulator for proper chromatin organization, silencing of sex chromosomes and crossover formation in male meiosis. PLoS Genetics.  [PMID: 29513658; PMCID: PMC5841650].