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John C. Herr
Education Grinnell College, B.A., 1970 University of Iowa , Ph.D.1978 ResearchOur 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. Representative Publications 1. P. Prabhakara Reddi, Marko Kalio, and John C. Herr 1999 Green flourescent protein as a reporter for promoter analysis of testis-specific genes in transgenic mice. Methods in Enzymology 302: 272-284. 2. Jagathpala Shetty, Soren Naaby-Hansen, Hiroaki Shibahara, Richard Bronson, Charles Flickinger, and John C. Herr 1999 Human Sperm Proteome Immunodominant sperm antigens identified with sera from infertile men and women. Biol. Reproduction 61: 61-69. 3. Charles J. Flickinger, Leigh Ann Bush, Mollie V. Williams, Soren Naaby-Hansen, Stuart S. Howards, and John C. Herr 1999 Post-obstruction rat sperm autoantigens identified by two-dimensional gel electrophoresis and western blotting. J. Reprod. Immunol. 43: 35-53. 4. John C. Herr, David Thomas, Leigh Ann Bush, Scott Coonrod, Vrinda Khole, Stuart S. Howards, and Charles J. Flickinger 1999 Sperm mitochondria-associated cysteine-rich protein [SMCP] is autoantigen in Lewis rats. Biol. Reprod. 61: 428-435. 5. Charles J. Flickinger, Mark Vagnetti, Stuart S. Howards and John C. Herr 2000 Antisperm autoantibody response is reduced by early repair of a severed vas deferens in the juvenile rat. Fertility and Sterility 73: 229-237. 6. John C. Herr, Kenneth L. Klotz, Peggy Anderson , Edward Adams, Norman Moore, and Stuart S. Howards 1999 Progress in developing an immunochromatographic device for seprm detection. Clinical Immunology Newsletter Vol. 19 (4/5): 52-58. 7. E.J. Norton, A.B. Diekman, V.A. Westbrook, C.J. Flickinger and John C. Herr 2001 RASA: An anti-sperm ScFv directed against the human sperm surface: Implications for novel contraceptives. Human Reprod. 16, (#9) 1854-1860. 8. Scott A. Coonrod, Paul W. Wright and John C. Herr. 2001 Oolemmal Proteomics. J. Reprod. Immunol. [in press] |