O'Brien Lab Rotation Projects

Molecular Regulation of Mammalian Spermatogenesis and Fertilization

My lab investigates molecular and cellular mechanisms that regulate spermatogenesis, sperm function and fertilization. Our studies use the male reproductive system as a model to investigate fundamental processes that control cell proliferation and differentiation. In terms of human health, the long-term goal of these studies is to provide new insights for the development of contraceptives, the clinical management of infertility, and the assessment of reproductive toxicants in the male.

Rotation projects can be developed in several areas, including:

  • Sperm metabolic transitions required for fertilization - Sperm undergo important changes in the female reproductive tract, including the phosphorylation of specific proteins and hyperactivated motility.  These changes also occur when sperm are incubated in medium that mimics the oviduct environment.  We are conducting detailed analyses of mouse and human sperm to determine the metabolic requirements for these physiological  transitions.
  • Male contraceptive development - GAPDHS, a sperm-specific isozymes in the glycolytic pathway, is essential for sperm motility and male fertility.  We are pursuing structure-based drug design to identify potent and selective inhibitors of GAPDHS that impair sperm metabolism and motility.
  • Genetics of male infertility - We are conducting extensive phenotypic and genotypic analyses of mouse lines becoming extinct during the generation of recombinant inbred strains in the Collaborative Cross.  We are also developing high throughput methods for assessing spermatogenesis and sperm motility.