Overview
In mammals, the primary step in male sex determination is the initiation of testis development in the bipotential gonad primordium. This step depends on the Y-linked male sex-determining gene, Sry. Expression of Sry in the XY gonad, or as a transgene in an XX gonad, leads to the differentiation of Sertoli cells. Failures in Sertoli cell differentiation in the XY gonad result in sex reversal and ovary formation. We are also interested in the biology of germ cells -- the cells that give rise to eggs and sperm. I have had a longstanding interest in the communication between Sertoli cells and germ cells in fetal life and afterwards, once the seminiferous epithelium is established. In adult life, each Sertoli cell communicates with germ cells at multiple stages of development from spermatogonial stem cells located at their base to elongated spermatids, released at their apical surface. How can Sertoli cells direct specific information to each of the germ cells wedged between their cell membranes? This problem previously seemed unapproachable, because it was so difficult to figure out where to anchor the analysis, and the cost of transgenics seemed prohibitive. However, recently we have been collaborating with a colleague in my department (Scott Soderling) who has designed an AAV system to deliver CRISPR and tag genetic loci in vivo with BioID for proximity protein labeling. We found that we can deliver the backbone AAV to Sertoli cell within seminiferous tubules with high efficiency by injection into the rete testis. Combining expertise of our labs provides an opportunity to do a similar analysis in Sertoli cells with the goal of identifying localized communication between Sertoli cells and the germ cells they support.
Current Appointments & Affiliations
James B. Duke Distinguished Professor of Cell Biology
·
2010 - Present
Cell Biology,
Basic Science Departments
Professor of Cell Biology
·
2005 - Present
Cell Biology,
Basic Science Departments
Member of the Duke Cancer Institute
·
1993 - Present
Duke Cancer Institute,
Institutes and Centers
Affiliate of the Duke Regeneration Center
·
2021 - Present
Duke Regeneration Center,
Basic Science Departments
Recent Publications
KDM6B is a conserved activator at the top of the male sex determination pathway.
Journal Article Development · June 15, 2025 In mammals, commitment to the testis fate is controlled by the gene Sry on the Y chromosome; however, how Sry is regulated is not well understood. In the red-eared slider turtle, Dmrt1 acts as the primary activator of the testis pathway. Removal of the rep ... Full text Link to item CiteIron deficiency in pregnant mice causes XY embryos to develop with female characteristics.
Journal Article Nature · June 2025 Full text CiteGranulosa cell death is a significant contributor to DNA-damaging chemotherapy-induced ovarian insufficiency†.
Journal Article Biol Reprod · May 13, 2025 Typically, DNA-damaging chemotherapy (CTx) regimens have a gonadotoxic effect and cause premature ovarian insufficiency (POI), characterized by infertility and estrogen deficiency. However, whether loss of granulosa cells killed directly by CTx contributes ... Full text Link to item CiteRecent Grants
Double Strand Break Repair in Fetal Male Germ Cells
ResearchSponsor · Awarded by National Institutes of Health · 2025 - 2027Building Interdisciplinary Research Careers in Women's Health - BIRCWH
Inst. Training Prgm or CMEMentor · Awarded by National Institutes of Health · 2002 - 2027Training Program in Developmental and Stem Cell Biology
Inst. Training Prgm or CMEMentor · Awarded by National Institutes of Health · 2001 - 2027View All Grants
Education, Training & Certifications
University of Pennsylvania ·
1989
Ph.D.