Jacquetta Trasler, MD, PhD
Our long term goal is to better understand normal and abnormal mammalian development. More specifically, we are using molecular and cell biology techniques to study the epigenome and how gene expression is regulated in developing germ cells and embryos and the implications for the resulting offspring. The epigenetic modification, DNA methylation, of specific gene sequences is an important component of a multi-level system that controls gene expression in mammalian cells. DNA methylation is first established during gametogenesis and has been implicated in genomic imprinting. Abnormalities in DNA methylation have been associated with abnormal development, genetic disease and cancer. Major differences in DNA methylation have been found between certain genes in the testis compared to those in the ovary and provide a way of marking the mother's and father's genes differently. We are testing the hypothesis that the establishment and maintenance of DNA methylation patterns in the germline and early embryo are essential for normal development; thus, altering these patterns is likely to interfere with cellular development and alter the function of germ cells in fertilization and early embryo development. Pharmacologic and genetic tools are used to alter DNA methylation during gametogenesis.
A second interest is to determine the molecular and cellular target for drug effects on developing male germ cells. In collaboration with other investigators, we are developing methods to monitor and prevent drug damage to the germ cells of patients treated for infertility and with anticancer drugs.
