Marvin L. Meistrich, Ph.D.
1967, Cornell University
The University of Texas M. D. Anderson Cancer Center
Department of Experimental Radiation Oncology
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Marvin L. Meistrich, Ph.D. 1967, Cornell University The University of Texas M. D. Anderson Cancer Center |
Research Interests:
Research in the Meistrich laboratory is in the area of male reproductive biology. Our major focus is on understanding the molecular events of the differentiation of the spermatogonia. The spermatogonial stem cells self-renew and give rise to differentiating spermatogonia that eventually develop into sperm. The differentiation of the spermatogonia is sensitive to disruption by toxicological exposure (e.g. radiation and chemotherapy) and genetic mutations and can result in sterility. We have made a very exciting discovery that testosterone, the hormone that is usually responsible for the stimulation of production of sperm in the normal male, can inhibit the initial stages of spermatogenesis in these pathological situations. We have shown that we can reverse this inhibitory process and restore fertility by hormone treatments that suppress testosterone levels. Based on our current data, we propose that testosterone stimulates the synthesis of a protein in Leydig cells that inhibits spermatogonial differentiation. We are currently elucidating the mechanisms, using different hormone treatments, in vitro culture, isolation of specific cell types, transplantation of specific testis cells between animals, analysis of differential mRNA expression, and modeling these effects in genetically engineered (transgenic, knockdown, and knockout) rodents.
Clinical applications of this research include restoration of fertility after radiation or chemotherapy for cancer (possibly with spermatogonial transplantation) and reversible contraception by blocking an early stage of sperm development.
Selected Publications:
Zhang Z, Shao S, Meistrich ML (2007) The radiation-induced block in spermatogonial differentiation is due to damage to the somatic environment, not the germ cells. J Cellular Physiol 211: 149-158.
Zhao M, Rohozinski J, Sharma M, Ju J, Braun RE, Bishop CE, Meistrich ML (2007) Utp14b: A unique retrogene within a gene that has acquired multiple promoters and a specific function in spermatogenesis. Develop. Biol., 304: 848-859.
Bolden-Tiller OU, Chiarini-Garcia H, Poirier C, Alves-Freitas D, Weng CC, Shetty G, Meistrich, ML (2007) Genetic factors contributing to defective spermatogonial differentiation in juvenile spermatogonial depletion (Utp14b/jsd) mice. Biol. Reprod. 77: 237-246.