Associate Professor
University of Pittsburgh
Dr. Walker has extensive experience in hormonal regulation of testis function, spermatogenesis and male fertility. His laboratory was the first to discover that testosterone can act via two mechanisms in Sertoli cells to support spermatogenesis. In the classical pathway, testosterone interacts with androgen receptor (AR) to directly regulate gene expression. In the non-classical pathway, testosterone acts via AR to activate numerous kinases, their target proteins and downstream gene expression in Sertoli cells.
Most recently, using pathway selective transgenic mouse models created by Dr. Walker, it was found that nonclassical activity allowed completion of meiosis and the production of haploid germ cells. Also, the first gene targets of AR-mediated signaling in meiotic germ cells that are essential for fertility were identified including classical pathway regulated cohesion and synaptonemal complex proteins that are essential for chromosome synapsis. The classical pathway was sufficient to produce sperm and fertility. However, added nonclassical activity contributed to maintaining the blood-testis barrier, plus correct migration and orientation of maturing spermatids needed for fully efficient sperm production. Classical activity alone partially restores male fertility, but nonclassical signaling is obligatory to maximize fertility.
Dr. Walker is using his mouse models and experience in characterizing hormonally regulated cellular pathways and communication to identify the altered intracellular factors present in benign prostate hyperplasia (BPH) and lower urinary tract symptoms (LUTS) that occur in association with aging. This information will be used to develop treatments for men with these disease states.