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Biochemistry and Molecular Biology

The 26th Annual Larry Ewing Lectureship

November 14, 2016

ewingDr. Ewing joined the School of Public Health in 1972 and over his time here his lab developed a method for the isolation of highly purified, steroidogenically active Leydig cells that is now used around the world.

He was the founder and later president of the Society for the Study of Reproduction, had over 130 major publications and held a patent on the sustained release of steroids for male contraception. Dr. Ewing had a significant impact on Reproductive Biology at Johns Hopkins University and we continue to build on his science today.

 

The Department of Biochemistry and Molecular Biology celebrated 26th Annual Larry Ewing Lectureship given by Dr. William Wright and entitled “The Spermatogonial Stem Cell Niche in the Fertile and Infertile Testis.”

 

wrightThe primary focus of Bill Wright’s career has been the study of interactions between spermatogenic cells and the somatic cells to which they bind, the Sertoli cells. Bill’s interests in reproduction and development began at Hamilton College where he studied with A. Duncan Chiquoine, the discoverer of the blood-testis barrier. Bill earned his Ph.D. in Biology from the State University of New York at Binghamton, working in the laboratory of Arthur Frankel. With Frankel, Bill performed some of the first analyses of androgen receptors in the testis. For a brief period, Bill also studied with Yves Clermont of McGill University. With Clermont, Bill became fascinated with the coordinated development of the different generations of the spermatogenic cells that surround a Sertoli cell. He pursued this interest as a postdoctoral fellow at the Population Council in New York, under the mentorship of C. Wayne Bardin. He also worked with Martti Parvinen of the University of Turku, investigating how Sertoli cell function changes as the adjacent spermatogenic cells progress through the stages of the cycle of the seminiferous epithelium. Stage-specific changes in Sertoli cell function remain a significant interest of Bill’s lab.

In 1982, Bill was appointed Assistant Professor in the Division of Reproductive Biology of the Department of Population Dynamics at what was then called the Johns Hopkins School of Hygiene and Public Health. He was promoted to Associate Professor in 1988 and to Professor with tenure in 1997. In 1998, the Division became part of the Department of Biochemistry and Molecular Biology. In 2008, Bill became Head of the Division of Reproductive Biology.

Bill’s research remains focused on the regulation and consequences of cell-cell interactions in the mammalian testis. His laboratory isolated a major stage-specific secretory product of rodent Sertoli cells, Cathepsin L, and demonstrated its involvement in sperm production. His laboratory identified the promoter that drives stage-specific transcription of the Cathepsin L gene in vivo, and proved that this pattern of transcription was due primarily to transcriptional repression at most states of the cycle. Additionally, his laboratory collaborated with Dan Johnston at Wyeth Pharmaceuticals to identify, by array analysis, all genes whose expressions varied in a stage-specific manner. A second important line of research for the Wright laboratory was the characterization of sperm surface receptors for the murine zona pellucida, the glycoprotein coat of mammalian eggs. In collaboration with Joel Shaper, two different sperm surface receptors were identified that bound with high affinity and in a structure – specific manner oligosaccharides. They also proved that in vitro, occupation of one of these receptors by oligosaccharides clustered on a polypeptide backbone triggered an essential step in fertilization, the acrosome reaction. Currently, the Wright laboratory is focused on how in the mature testis Sertoli cells regulate the numbers, replication and differentiation of spermatogonial stem cells (SSCs). These studies use an in vivo chemical-genetic approach that allows for the transient inhibition of signaling from the Sertoli cell product, glial cell line-derived neurotrophic factor (GDNF). His lab has demonstrated that GDNF stimulates replication and suppresses the differentiation of SSCs and their immediate progeny, progenitor spermatogonia. They have also shown that sustained inhibition of GDNF signaling produces a testis whose histology mimics that of infertile, Sertoli cell-only human testes.

In addition to his research, Bill has played important roles in his scientific community and in the university. He has served on a number of different study sections, including Reproductive Biology and has chaired the Contraceptive Development Study Section. He has served as a member of the editorial boards of the journals Endocrinology and Biology of Reproduction, and was program chair for the 2013 North American Testis Workshop and the 2015 Annual Meeting of the American Society of Andrology.

PHOTOS COURTESY OF  TARA BISER 
 
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