# Spermatogenic gene regulation and infertility > **NIH NIH P50** · CORNELL UNIVERSITY · 2024 · $1,614,188 ## Abstract The Cornell Center for Reproductive Genomics (CRG) was founded in 2007 with the goal of leveraging state-of- the-art genomics technologies for understanding the biology of the mammalian germ cell. More specifically, our goal has been to understand the genetic, epigenetic, and epitranscriptomic basis for the generation of viable healthy gametes and to explore how alterations in these events could contribute to human infertility. It is well known that disruption of genes required for regulating all aspects of gene expression, including chromatin modifiers, the transcription machinery, and components of post-transcriptional regulatory pathways, leads to the formation of spermatozoa with abnormal head morphology in the mouse, while sperm from men with increased abnormal sperm morphology significantly higher rates of chromosomal aneuploidy, chromatin compaction defects, and altered transcriptome profiles compared to sperm from fertile men. Thus, in this application, we seek to understand how transcriptional, post-transcriptional, and epitranscriptomic regulation of gene expression and chromatin state contributes to the differentiation of haploid germ cells into mature spermatozoa. Three projects are proposed and three cores are proposed. PROJECT I (Danko and Cohen) will focus on the importance of transcriptional regulation of gene expression at the exit from meiosis and entry into spermiogenesis, with a focus on the role of the bromodomain protein, BRDT in facilitating transcriptional shutdown and thus permitting appropriate histone-to-protamine replacement and nuclear compaction. PROJECT II (Grimson, Schimenti, Hwang) will focus on mechanisms and functions of post-transcriptional processing and regulation of mRNAs during spermiogenesis and whether defects in these processes can underlie defects in sperm morphology in patients seeking assisted reproductive technologies. PROJECT III (Jaffrey) will explore the dynamics of N6-methyladenosine (M6A) and N6, 2’-O-dimethyladenosine (m6Am) modifications on RNA through spermatogenesis in mice and in men, and the importance of these epitranscriptomic changes for the production of healthy sperm in mice and men. These studies will be supported by a well-established ADMINISTRATIVE CORE (Cohen) that will facilitate close interactions through regular meetings, trainee events, pilot and seed grants, and our popular “Tri-Repro” Annual Symposium. Our state-of- the-art GENOME INNOVATION CORE (Grenier) will serve as an Innovation Hub for exploring all aspects of gene regulation in reproduction, specializing in a range of next generation sequencing technologies to support the projects. Finally, our OUTREACH CORE (Lin) will provide lab opportunities for nearby, and traditionally underserved, school districts throughout upstate New York, at the same time sending our trainees and faculty out to these communities as role models for young budding scientists. Our center will benefit from the strong research and clinical integra... ## Key facts - **NIH application ID:** 10828818 - **Project number:** 5P50HD104454-04 - **Recipient organization:** CORNELL UNIVERSITY - **Principal Investigator:** Paula Elaine Cohen - **Activity code:** P50 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $1,614,188 - **Award type:** 5 - **Project period:** 2021-05-01 → 2026-03-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10828818 ## Citation > US National Institutes of Health, RePORTER application 10828818, Spermatogenic gene regulation and infertility (5P50HD104454-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10828818. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*