William Walker, PhD

Associate Professor of Obstetrics, Gynecology and Reproductive Sciences

Research

The major focus of the Walker Research Group is to define how hormonal and environmental signals are transduced into the signals that maintain spermatogenesis and male fertility. Dr. Walker studies the regulation of spermatogenesis by the Sertoli cell in the mammalian testis as well as the maintenance of spermatogonial stem cells. Mouse, rat and rhesus monkey testes are used as model systems to determine how follicle-stimulating hormone, testosterone, and other hormones alter cellular signaling pathways to regulate the genes, enzymes and structural proteins that are required for male fertility. Dr. Walker uses biochemical, cell biological, transgenic and bioinformatics techniques. These strategies are used to study 1) the signals acting on Sertoli cells that are required to support the development of sperm 2) the mechanisms by which the SHP2 tyrosine phosphatase functions in spermatogonial stem cells to maintain self-renewal and fertility 3) the signals produced at the initiation of puberty that permit spermatogonial stem cell differentiation and sperm production.

The classical and non-classical pathways of testosterone signaling in Sertoli cells.

The classical and non-classical pathways of testosterone signaling in Sertoli cells.

 

Specific Areas of Research Include:

  • The molecular mechanisms by which testosterone acts in the Sertoli cells to support male fertility.
  • The regulation of Sertoli cell differentiation.
  • Signals that determine whether male germ line stem cells in the testis self-renew or differentiate.
  • Evaluation of candidate male contraceptive and sterilant drugs
SHP2 expression (red) in a mouse testis cross-section.

SHP2 expression (red) in a mouse testis cross-section.

 

Selected Publications

  • Walker WH, Easton E, Moreci RS, Toocheck C, Anamthathmakula P, Jeyasuria P. Restoration of Spermatogenesis and Male Fertility Using an Androgen Receptor
    Transgene. PLoS ONE (2015) 10(3): e0120783.
  • Toocheck C, Clister T, Shupe, J, Crum C, Ravindranathan R, Lee T-K, Ahn J-M, Raj GV, Sukwani M, Orwig KE, Walker WH. Classical and non-classical testosterone signaling are required for spermatogenesis. Biology of Reprod. (2015) 94(1):11.
  • Smith LB, Walker WH. Hormone Signaling in the Testis. In: Plant TM, Zeleznik AJ, editors-n-chief. Albertini DF, Goodman RL, Herbison AE, McCarthy MM, Muglia LJ, Richards JS, associate editors. Knobil and Neill’s Physiology of Reproduction (Fourth Edition). Vol. 1. Oxford: Elsevier Academic Press; 2014. p. 632-90.
  • Smith LB, Walker WH. The regulation of spermatogenesis by androgens. Semin Cell Dev Biol. 2014;30-2-13.
  • Puri P, Phillips BT, Suzuki H, Orwig KE, Rajkovic A, Lapinski P, King P, Feng G-S, Walker WH. The Transition From Stem Cell to Progenitor Spermatogonia and Male Fertility Requires the SHP2 Protein Tyrosine Phosphatase. Stem Cells. 2014;32:741-53.
  • Puri P and Walker WH. The tyrosine phosphatase SHP2 regulates Sertoli cell junctional complexes. Biol Reprod. 2013;88:59, 1-11.
  • Shupe J, Cheng J, Puri P, Kostereva N, Walker WH. Regulation of Sertoli-germ cell adhesion and sperm release by FSH and non-classical testosterone signaling. Mol Endocrinol. 2011 Feb;25(2):238-52.
  • Walker WH. Non-classical actions of testosterone and spermatogenesis. Philos Trans R Soc Lond B Biol Sci. 2010 May 27;365(1546):1557-69. Review.
  • Gassei K, Ehmcke J, Wood MA, Walker WH, Schlatt S. Immature rat seminiferous tubules reconstructed in vitro express markers of Sertoli cell maturation after xenografting into nude mouse hosts. Mol Hum Reprod. 2010 Feb;16(2):97-110.
  • Viswanathan P, Wood MA, Walker WH. Follicle-stimulating hormone (FSH) transiently blocks FSH receptor transcription by increasing inhibitor of deoxyribonucleic acid binding/differentiation-2 and decreasing upstream stimulatory factor expression in rat Sertoli cells. Endocrinology. 2009 Aug;150(8):3783-91.
  • Walker WH. Molecular mechanisms of testosterone action in spermatogenesis. Steroids. 2009 Jul;74(7):602-7. Review.
  • Wood MA, Walker WH. USF1/2 transcription factor DNA-binding activity is induced during rat Sertoli cell differentiation. Biol Reprod. 2009 Jan;80(1):24-33.

For additional publications, see: http://www.ncbi.nlm.nih.gov/sites/myncbi/williamh.walker.1/bibliograpahy/41976244/public/?sort =date&direction=ascending

 

Patents pending:

Patent PAC/US2014/0344800. “Sterilization Method” This patent is for the use of inhibitors of the SHP2 phosphatase to sterilize male companion animals including dogs and cats.

 

The SHP2 inhibitor NSC 87877 permanently eliminates sperm production in pig testis.

The SHP2 inhibitor NSC 87877 permanently eliminates sperm production in pig testis.