My research interests are to understand the transcription regulation and signal transduction pathways involved in normal development, stem cell maintenance and differentiation, in cancers and other human diseases at molecular level. The importance of maintaining correctly controlled transcription is emphasized by the observation that various pathologies arise due to the mutation of genes encoding components of transcription machinery or pathways, which modify their activity. As a Research Associate scientist at University of Washington and now at The Jackson Laboratory I have been studying the role of genes involved in self-renewal and differentiation of germline stem cells. I have address the role of Ztbt16, Gfra1, Eomes, Lin28, Gdnf, and Sin3a genes in maintaining the stem cell properties.
Adult germline stem cells are capable of self-renewal, tissue regeneration and production of large numbers of differentiated progeny. We show here that the classical mouse mutant luxoid affects adult germline stem cell self-renewal. Young homozygous luxoid mutant mice produce limited numbers of normal spermatozoa and then progressively lose their germ line after birth. Transplantation studies showed that germ cells from mutant mice did not colonize recipient testes, suggesting that the defect is intrinsic to the stem cells. We determined that the luxoid mutant contains a nonsense mutation in the gene encoding Plzf, a transcriptional repressor that regulates the epigenetic state of undifferentiated cells, and showed that Plzf is coexpressed with Oct4 in undifferentiated spermatogonia. This is the first gene shown to be required in germ cells for stem cell self-renewal in mammals.