People

P. Jeremy Wang, M.D., Ph.D.

Ralph L. Brinster President's Distinguished Professor
Director, Center for Animal Transgenesis & Germ Cell Research

 

School of Veterinary Medicine University of Pennsylvania
Dept of Biomedical Sciences
390EC Rosenthal Bldg
3800 Spruce Street

My research focuses on the study of spermatogonial stem cells and meiosis. Spermatogonial stem cells are the adult germline stem cells and responsible for life-long production of sperm. Meiosis, a cell division unique to germ cells, allows the reciprocal exchange of genetic material between paternal and maternal genomes. In the past 20 years, my laboratory has focused on understanding the regulation of meiosis by assessing the function of a number of novel meiosis-specific proteins identified in my lab. On one hand, our studies provide molecular insights into the development of germ cells in mice. On the other hand, these mouse studies have important implications for understanding the genetic causes of male infertility in humans. We have performed two innovative cost-effective genome-wide screens, which represent significant contributions to the field of reproduction. In the first screen, we employed a cDNA subtraction approach and identified 36 germ cell-specific genes expressed in mouse spermatogonia, 24 of which were novel at that time. Since then, my lab has published genetic and functional studies on more than 10 of these genes including the X-linked gene TEX11. This study demonstrated that the X chromosome plays a disproportionately eminent role in male fertility, challenging the dogma that the X chromosome is a female chromosome. Indeed, we have shown that TEX11, an X-linked gene, is essential for male fertility in mice and men. In the second genome-wide screen, we undertook a proteomics approach and identified 51 meiotic chromatin-associated proteins in mouse, 32 of which were uncharacterized. To date, we have published functional studies of MEIOB, SCML2, UTF1, YTHDC1, YTHDC2, and SKP1, six of the proteins identified in our proteomics screen. In addition, we have shown that DOT1L, histone H3K79 methyltransferase, is essential for self-renewal of spermatogonial stem cells. These functional and mechanistic studies have had high impacts on our understanding of spermatogonial stem cell renewal, meiotic recombination, piRNA biogenesis, retrotransposon silencing, and male infertility in humans. Therefore, these two genome-wide screens and many functional studies represent significant contributions to the field of mammalian reproduction. In the future, we are interested in the biochemical, molecular, and genetic functions of these proteins in transcription, meiotic recombination, and epigenetic reprogramming in germ cells.

Research Interest

The research in the Wang laboratory focuses on epigenetics in reproduction, spermatogonial stem cell self-renewal, silencing of transposable elements, regulation of meiosis, DNA double-strand break repair, piRNA biogenesis, and male infertility in humans.