university of pittsburgh
center for research in reproductive physiology
 
university of pittsburgh school of medicine
 
 

Faculty and Research Interests

William H. Walker
Ph.D., University of Texas Health Science Center at Houston

The goal of the Walker laboratory is to identify the genes and their regulatory factors in the testis that are critical for the initiation and progression of spermatogenesis.

One focus is to define how the CREB transcription factor controls the expression of Sertoli cell genes that are essential for germ cell survival. Our recent studies demonstrate that the introduction of an inactive CREB mutant into Sertoli cells results in the near complete elimination of sperm production. To identify CREB dependent genes in vivo, we are injecting rat testes with adenovirus vectors designed to modulate CREB transcriptional activity. Laser capture microscopy is used to specifically isolate adenoviral infected Sertoli cells and extracted RNA is assayed for altered gene expression by quantitative, real time PCR as well as gene microarray technology.

A second goal is to characterize the function of the NF-kB transcription factor in Sertoli cells. Originally identified in our lab as an activator of CREB gene transcription, we have also found that NF-kB stimulates androgen receptor expression and thus NF-kB likely contributes to the maintenance of spermatogenesis by androgen. Studies are underway to determine the mechanisms responsible for the relatively high levels of NF-kB activity that are displayed by Sertoli cells and to identify additional NF-kB-regulated genes.

A third objective is to identify targets for male contraception mechanisms using a naturally occurring model of aspermatogensis. Sertoli cells from male neonate monkeys, that have adult levels of all essential reproductive hormones yet produce no sperm, are being studied to identify possible deficiencies in the follicle-stimulating hormone and testosterone mediated signaling pathways.

Representative Publications

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