Professor and Chair
Department of Cell Biology Georgetown University Medical Center
SW209 Basic Science Building, Box 571436
4000 Reservoir Road, NW
Washington, DC 20057
Phone: 202 687-1157
Fax: 202 687-9864
Male germ line stem cells
Germ line genetic engineering is one of the last frontiers in medicine to be conquered. The concept that is being developed is to change the male human genome in a heritable way; i.e., to fix all known errant genes in the sperm. These would be permanent repairs to be passed from one generation to the next. Type A spermatogonia are the male germ-line stem cells. Our laboratory has succeeded in isolating, purifying, and characterizing these stem cells. With the long-term goal of germ cell gene therapy, we are currently focusing on the understanding of the factors that regulate the renewal and differentiation of the spermatogonial stem cells. In recent years, we have demonstrated the presence of c-kit receptor and LIF receptor on the spermatogonial stem cells. Signal transduction pathways are being characterized upon activation of these receptors with specific ligands. As a preliminary effort, modification of the genome of type A spermatogonia is being attempted using modern approaches to gene modification and transfer, i.e., retroviral transfer of specific genes. Using similar molecular approaches, we immortalized the spermatogonial stem cells. The overall interest of our laboratory is to understand the process of mammalian spermatogenesis with special focus on spermatogonial stem cell regulation, genetic modification and transplantation.
- Feng LX, Ravindranath N, Dym M. SCF/c-kit up-regulates cyclin D3 and promotes cell cycle progression through the PI3-K/AKT/mTOR/p70S6K pathway in spermatogonia. J Biol Chem 275:25572-25576, 2000.
- Dirami G, Ravindranath N, Achi MV, and Dym M. Expression of Notch pathway components in spermatogonia and Sertoli cells of neonatal mice. J Androl 22:944-952, 2001
- Feng LX, Dettin L, Chan Y, Dettin L, Reijo Pera RA, Herr JC, Goldberg E and Dym M. Generation and in vitro differentiation of a spermatogonial cell line. Science 297:392-395, 2002 [June 20 epub ahead of print].
- Anway MD, Ravindranath N, Dym M, and Griswold MD. Identification of a murine testis complementary DNA encoding a homologue to human a-kinase anchoring protein-associated sperm protein. Biol Reprod 66:1755-1761, 2002.
- Hofmann MC, van der Wee K, Dargart J, Dirami G, Dettin L, and Dym M. Establishment and Characterization of a Mouse Sertoli Cell Line. J Androl 24:120-130, 2003.