1972 B.A., Rutgers College
1982 Ph.D., University of Pennsylvania
Mechanisms of Fertilization
Fertilization is the process by which sperm and egg fuse and the program of development is initiated. This is controlled in mammals at two steps: 1) sperm first undergo “capacitation”, a physiological reprogramming that occurs within the female reproductive tract and that is essential for the expression of fertility; and 2) capacitated sperm interact with the egg. Our work has focused on the molecular and cellular mechanisms that control these two events. To this end, we apply a range of biophysical (single cell fluorescence imaging, patch clamp electrophysiology), biochemical and molecular techniques.
Studies of capacitation address the control of sperm signal transduction pathways that lead to fertility. Ion fluxes are important regulators of this process and we have identified key roles of sperm membrane potential and pH. In addition, we recently recognized a role of polycystic kidney disease proteins in capacitation. Ongoing and future studies address the mechanisms by which factors from the female reproductive tract regulate these and other pathways, leading to sperm fertility.
Sperm-egg interaction begins when sperm contact the egg extracellular matrix (the zona pellucida). ZP3, a protein component of the zona pellucida, activates sperm and triggers a secretory event known as the acrosome reaction. This is an obligatory event in gamete interaction that must be completed if sperm are to fuse with eggs, and disruption of the zona pellucida-evoked acrosome reaction is linked to several types of male infertility. We have worked on the signal transduction cascade that is regulated by ZP3. Specifically, we have focused on the intersecting roles of Ca2+ and Ca2+ channels, of phosphatidylinositol pathways, and protein kinases in the control of the acrosome reaction.