|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. For further information, see the recent lecture by Dr. Paula Cohen, given as part of Cornell University's 150th Anniversary Lecture Series.
|2. Maintenance of genome integrity in the mammalian germline||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):
A new study from Andrew Grimson's lab, in collaboration with Paula Cohen's lab, has identified a key pathway required for maintenance of sex chromosome telomere integrity. Using conditional knockout mice for Dicer and Dgcr8, two key enzymes required for small RNA processing, Modzelewski et al (2015) show that loss of small RNAs during prophase I leads to telomere fusion events specifically involving the X and Y chromosomes. For further information, see the May edition of Journal of Cell Science
A recent publication by Dabaja et al (2015) has identified key cell:cell interactions that are necessary to establish normal profiles of one key microRNA, miR202-5p, in Sertoli cells. This is the first example of a germ cell regulatory interaction that is necessary for miR expression in neighboring somatic cells of the testis
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.