Research TopicsDepartment of Veterinary Biosciences
Ph.D. (1982) University of Pennsylvania
Research Topics
Research Interests
The overall aim of my research is to elucidate the mechanism(s) of cellular differentiation at the level of gene regulation. We use mammalian spermatogenesis, a unique cellular differentiation pathway, to study the processes that control the expression or repression of cell-stage specific genes. Starting at the stem cell stage, spermatogenesis proceeds through a series of defined cell types. The germ cells undergo mitosis, meiosis, and morphological restructuring of the terminal cell stages to produce mature spermatozoa. During this process the cell exhibit a differential temperature sensitivity and many testis-specific genes, somatic genes, and testis-specific variants of somatic genes become differentially expressed. Groups of genes are activated while others are turned off. These changes in stage-specific gene transcriptional control mechanisms governing the activation or inactivation of temporally expressed genes.
To study the transcriptional regulation of post-meiotic expressed genes, we developed in vitro transcription system derived from mouse or rat testis. Fractionation and reconstitution of the transcription extract is being used to characterize and isolate a gene repressor activity and a testis-specific temperature sensitive component of RNA polymerase II. We are interested in extending the use of the in vitro system to study regulatory mechanisms in mitotic and meiotic germ cell stages as well. To augment this work on gene transcription we are additionally involved in the cloning and characterization of genes novel to the process of spermatogenesis.
Other pursuits of my laboratory involve a collaborative study on the role of locally synthesized estrogen in the development and maturation of the male germ cell. We expect that our research will in the future provide basic new information on how transitions in gene regulation are brought about in a differentiating cell system. This work also could have important consequences for specifically controlling germ cell differentiation at various stages of spermatogenesis, positively or negatively.
Key Words Recombinant DNA, Introduction of DNA into Animal Cells, Gene
Expression Systems, DNA-Protein Interactions, Animal Cell and/or Tissue Culture,
Transgenic Animals, Site-Directed Mutagenesis, Protein Purification and Characterization
Current Research Funding
NIH