In the past fifteen years, since the discovery of RNA interference (RNAi), it has become clear that small RNA pathways play essential roles in the regulation of gene expression across the animal and plant kingdoms. Nowhere is this more true than in the germline, where specific small RNAs, the PIWI-interacting RNAs (piRNA), reside alongside small interfering RNAs (siRNA) and microRNAs (miRNA). The field has evolved at an alarmingly fast pace, and it is now apparent that small RNAs are likely to be key to many human diseases, the etiology of which have hitherto been unclear. The field of reproductive medicine is likely to lead the way in such studies, both because of the huge interest in piRNAs, and also because of the availability of human gametes for study. In this regard, researchers and physician-scientists within Cornell Center for Reproductive Genomics (CRG) represent an outstanding resource to the clinical community at large for providing tools, techniques, and knowledge to their colleagues interested in small RNA biology in different physiological systems. At the same time, given that RNAi mechanisms are at the cutting edge of medical research, CRG researchers can provide an essential conduit for the flow of information from the research lab to the patient. Thus, the goals of this outreach core are two-fold: (1) to provide a scientific and technical resource for clinicians interested in embarking on research involving small RNA biology in their physiological system of interest, and (2) to provide outreach to the community by means of a state-of-the-art lecture series, The Innovation Seminars in Reproductive Technologies Series (InSeRT), in order to educate patients about the latest advances in our understanding of the genetic and epigenetic basis for human disease. In both aims, investigators from Weill Cornell Medical College and from the Colleges of Cornell University in Ithaca, NY, will join forces to provide comprehensive education to scientists, physicians, and the public alike.
The Outreach Core is headed by Dr. Peter Schlegel, with Drs. Paula Cohen and Darius Paduch serving as co-Directors. Dr. Cohen will co-ordinate all requests for training from outside of Cornell, and will host visitors from Weill Cornell Medical College and beyond on the Ithaca campus, which serves as the home of the RNA sequencing core along with many CRG-affiliated labs. Drs. Schlegel and Paduch will co-ordinate training on the Weill Cornell campus. For enquiries and training opportunities, please contact Elena Cestero.
Seminars are held in the evening at the campus of Weill Cornell Medical College, on the Upper East Side in Manhattan. Speakers are selected for their worldwide recognition as leaders in the field of stem cell biology and human fertility. Our first speaker in 2014 was Dr. Renee Reijo Pera from Montana State University. Stay tuned for more seminars in 2015.
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.