Scott Coonrod, PhD
Laboratory of Epigenetics and Reproductive Biology
Once ovulated, the terminally differentiated mammalian oocyte will die if it does not bind and fuse with a sperm. If fertilization occurs, however, maternal gene products orchestrate the transformation of the egg into a totipotent zygote within hours. My lab is investigating the role that novel, highly-abundant, and egg-restricted molecules play in this reprogramming process. Currently, we are focusing on one such gene product, peptidylarginine deiminase 6 (PADI6) which we have localized to a poorly characterized egg-restricted structure, the cytoplasmic lattices (CPLs). The CPLs, which occupy about twenty percent of the egg cytoplasm, have been described in the literature for over 40 years, yet their function remains poorly defined. Through use of mouse knockout models, we have discovered that PADI6 is required for CPL formation during oogenesis, thus suggesting that PADI6 is an integral component of the CPL complex. Further, we have found that PADI6 is required for development beyond the two-cell stage, thus indicating that PADI6 represents one of a handful of known mammalian factors that are produced by the mother and then endowed to the embryo to help manage the early stages development. Currently, we are exploring the mechanisms by which PADI6 and the CPLs regulate embryonic reprogramming and, more specifically, are investigating whether PADI6 plays a direct role in the establishment of totipotency during embryonic genome activation at the two-cell stage via cytoplasmic-to-nuclear signaling events.
In order to reduce the incidence of breast cancer, a primary goal of breast cancer research over the last 30 years has been to identify and characterize genes that are mutated in breast tumors. While this research has uncovered numerous gene mutations that play important roles in breast cancer, the incidence and mortality of breast cancer remains relatively high suggesting that other non-genetic factors are likely involved. Epigenetic chromatin modifications such as DNA methylation and histone modifications have been found to play central role in regulating the expression of genes during development. These epigenetic modifications do not alter the DNA sequence yet can be inherited from one cell generation to the next. Recently, scientists have found that dysregulation of the normal epigenetic profile in several different tissue types can lead to cancer. Therefore, another long term goal of my lab is to establish whether the onset of breast cancer is mediated by epigenetic mechanisms. More specifically, we have recently found that another member of the PADI enzyme family, PADI4, can place a novel histone modification, called citrulline, on genes that are normally activated by estrogen, thereby suppressing their activity. Given the strong link between estrogen and some types of breast cancer, our findings suggest that PADI enzymes may play an important role in breast cancer. Thus, major goal of the breast cancer project are to determine how PADI4 regulates the estrogen response in breast cancer cells and to investigate whether PADI4 play a direct role in the formation of breast tumors.
Link to Cornell's CyberTower website which is currently highlighting Dr. Coonrod's research in fertilization and early development.
Link to Dr. Coonrod's powerpoint lecture (with audio) on non-surgical strategies for contraception in companion animals.