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Faculty Appointment:
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Department of Obstetrics and Gynecology
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| Research Interests: |
My research examines the function of novel phosphatase-related proteins involved in reproduction and disease. Each of the proteins under study can be classified within the large superfamily of protein tyrosine phosphatases (PTPs). However, we have discovered a phospho-serine, -threonine or -tyrosine interaction protein, STYX, as the archetype of a new class of so-called, dead-phosphatases, which structurally mimic PTPs except for the endogenous substitution of catalytically essential amino acids. Rather than simply being the non-catalytic relic of an active phosphatase, STYX serves as an adapter to phosphorylated protein targets and plays an essential role in spermatogenesis. Our knockout model of Styx function in mouse leads to male infertility due to the disruption of the differentiation of spermatids into spermatozoa. Endogenous expression of Styx in round spermatids and its coimmunoprecipitation with a multiply phosphorylated spermatid RNA-binding protein suggests that together they form a translational checkpoint governing germ cell differentiation.
Our work with Styx has led to the identification of another dead-phosphatase, Sbf-1, whose loss of expression in mouse results in Sertoli cell dysfunction and azoospermia. We can show that Sbf-1 physically interacts with a catalytically active lipid phosphatase found in Sertoli cells, through which Sbf-1 likely modulates intracellular phosphoinositide signaling and vesicular trafficking. Finally, we have also discovered a new
egg-derived lipid phosphatase, EDP, which is involved in vesicular sorting of lysosomes and autophagic vesicles. Our recent knockout of EDP in mouse and ongoing characterization of Styx and Sbf-1 function, promises to expand our basic understanding of normal reproduction and reproductive pathophysiology, as well as reveal new targets for contraceptive intervention in humans.
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Education and Credentialing: |
| Degree: |
Ph.D., 2000, University of Michigan
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