The CRG was founded in 2006 with a mission to promote state-of-the-art research in reproductive health and fertility. Our area of expertise focuses on, but is not limited to, gamete biology, with an emphasis on the genetic and epigenetic mechanisms that regulate the formation of viable gametes for sexual reprodution. The strength of the center lies in its strong ties between the basic scienes, based largely on the Ithaca campus of Cornell, and the clinical sciences, focussed in Manhattan, NY, within the Weill Cornell Medical College. In addition, the translational aspects of research extend to our strong interests in animal health, due in part to the home college for the CRG being the College of Veterinary Medicine. Research in the CRG spans many aspects of reproductive health, but its funding base is centered on three distinct missions, all focussed on reproduction, fertility, and women's health:
|1. Non-coding RNAs and their role in the regulation of gametogenesis (sponsored by an NICHD-funded P50 award)||In April 2014, we were awarded a U54 Center grant as part of the NICHD Specialized Co-operative Centers Program in Reproduction (SCCPIR). This program has since been converted to a P50-sponsored mechanism and is now entitled The National Centers in Translational Research in Reproduction and Infertility (NCTRI). Our Center funding focuses on our research involving small RNA-mediated regulation of gametogenesis, but we have several lines of research focus beyond this.|
|2. Maintenance of genome integrity in the mammalian germline (a P01 proposal has recently been submitted)||Our studies seek to characterize the important genetic quality control mechanisms that operate during different stages of mammalian gametogenesis in both sexes, using genomic, proteomic and transgenic technologies in the mouse model. The projects are led by 4 highly interactive investigators, Drs. Schimenti, Weiss, Smolka, and Cohen, each specializing in the areas of reproductive biology, DNA replication and repair, meiosis, proteomics of DNA damage signaling, and mouse genetics. Studies are aimed at understanding key molecular mechanisms preserving the genetic integrity of our germlines, enabling us to detect, prevent, and possibly reverse risk factors that could perturb these mechanisms and predispose to reproductive health issues or transmission of birth defects to offspring.|
|3. Reproductive Genomics Training Grant (sponsored by the NICHD)||We are in the 9th year of our NICHD-funded T32.We support both predoctoral fellows and postdoctoral fellows. The Principal Investigator of the T32 is Mark Roberson.|
Our areas of research focus include (amongst others):
The Smolka Lab have developed a novel strategy for monitoring Mec1/Tel1 (ATR/ATM) signaling in budding yeast, and show that Mec1 has distinct "replication-correlated" activity that is distinguishable from its action during canonical damage-induced checkpoint activation. This research is published in the March 2015 issue of Molecular Cell
Members of the Center for Reproductive Genomics were awarded a U54 grant to study the role of small RNAs in gametogenesis. Paula Cohen is PI of this grant (which was recently converted to a P50), and the grant includes projects from Drs. Andrew Grimson and Darius Paduch, together with a pilot project from Dr. John Schimenti. An RNA Sequencing Core has been established and is led by Drs. Andrew Grimson and Jen Grenier.
The lab of Center member John Schimenti recently identified the DNA damage checkpoint pathway responsible for culling oocytes that fail to repair double stranded breaks (DSBs) that occur during meiosis or which arise in a female's oocyte pool (Bolcun-Filas et al, Science 343:533-536, 2014). Using combinations of mutants involved in recombination and DNA damage responses, they found that this pathway involves signaling of checkpoint kinase 2 (CHK2) to both p53 and p63. Disruption of this checkpoint pathway restored fertility to females that normally would be deficient of all oocytes due to defects in meiotic recombination or exposure to radiation. This discovery opens the way to using available CHK2 inhibitors to protect the oocytes of women undergoing cancer therapy that would normally cause infertility.