Research in my Laboratory is focused on:
I.) Regulation of Large-Scale Chromatin Structure and Epigenetic Control of Gene Expression during Oogenesis
Chromatin configuration in the nucleus or germinal vesicle (GV) of mammalian oocytes undergoes dynamic epigenetic modifications during oocyte growth. A crucial developmental transition at the culmination of oogenesis, large-scale chromatin remodeling in the GV is essential to confer the female gamete with meiotic and developmental potential. Using several models for the experimental manipulation of chromatin structure and function in combination with cell and molecular biology approaches our current work seeks to determine the cellular pathways and factors that are involved in remodeling chromatin in the mammalian oocyte genome.
II). Role of Chromatin Modifications during Meiosis
Centromeric heterochromatin formation is essential for chromosome architecture, transcriptional silencing and chromosome segregation.
However, little is known concerning the epigenetic control of heterochromatin formation in the mammalian germ line. Using RNA interference (RNAi) we have begun to explore the role of ATRX, (a heterochromatin binding protein with chromatin remodeling activity) during meiosis. ATRX is present at centromeric domains in the germinal vesicle of mouse oocytes and becomes exclusively associated with centromeres of chromosomes at metaphase I or metaphase II of meiosis, where it is required to mediate chromosome-microtubule interactions in the female gamete. Moreover, we currently study the role of the lymphocyte-specific helicase (LSH) on meiotic chromosome synapsis, heterochromatin formation and maintenance of genomic stability in the female germ line.
"Mice that are homozygous for the poly(ADP-ribose) polymerase-1 null mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Although a shortened transcript is generated, no enzymatic activity is detected in tissues. Proliferation of homozygous fibroblasts and thymocytes is impaired following gamma-radiation in comparison to cells derived from wildtype mice. Older mice are susceptible to spontaneous development of skin disease. A significant portion of older mice (~30%) can be expected to exhibit epidermal hyperplasia. Null mice are also less susceptible to damage induced by the neurotoxin MPTP."