Our laboratory is focused on the structural characterization of sperm proteins and their encoding genes. Two fundamental concepts underlie this work. First, during spermatogenesis, the expression of genes unique to the spermatogenic lineage, results in sperm-specific polypeptides being incorporated into the sperm's cyto architecture. Such testis-specific genes provide good models for understanding the regulation of gene expression during the differentiation of spermatids into mature sperm. Second, the sequestration of sperm from the immune system by the blood-testis barrier allows for many sperm antigens to be recognized immunologically as autoantigens.
The goals of our laboratory are to identify sperm proteins which are testis-specific, to understand which are autoantigens, and to identify when these proteins arise during spermatogenesis and how they are arranged within the mature sperm cell. Particular attention is given to understanding the fate of these proteins during events in the life of a sperm, such as the acrosome reaction and sperm-egg interactions during fertilization. In the process of obtaining primary amino acid sequence data on testis-specific proteins, both cDNA and genomic sequencing is conducted, including analysis of 5' regulatory regions. A basic interest in this work is to identify cis and trans acting factors regulating testis-specific genes at precise stages of spermatogenesis.
A clinical application of this research is the development of multideterminant recombinant contraceptive vaccines based upon testis-specific sperm surface proteins. The laboratory is engaged in formulating contraceptive vaccines based on recombinant sperm proteins expressed in bacteria. Following expression and purification of these recombinant sperm antigens, the immunogenicity and contraceptive effects of these vaccine formulations are studied in mice, baboons and monkeys.
Recent research objectives have involved characterization and testing the efficacy of a contraceptive vaccine based upon the sperm-specific immunogen, SP-10. This immunogen was identified as a primary vaccine candidate by the WHO Task Force on Vaccines for Fertility Regulation.