Small RNA Pathways in Mammalian Gametogenesis
| Status: | Recruiting |
|---|---|
| Conditions: | Women's Studies, Infertility |
| Therapuetic Areas: | Reproductive |
| Healthy: | No |
| Age Range: | 18 - 90 |
| Updated: | 5/9/2018 |
| Start Date: | April 2014 |
| End Date: | March 2019 |
| Contact: | Lauren H Chen |
| Email: | luc2013@med.cornell.edu |
| Phone: | 2127465706 |
Basic and clinical research is revealing that various noncoding and small RNAs play important
and diverse roles in germ cell development and quality, including X/Y silencing during
meiosis, gene regulation, DNA damage responses, and protection of the genome against
transposable elements. Indeed, mammalian germ cells are known to harbor multiple small RNA
species, including small interfering RNAs (siRNA), microRNAs (miRNA), and germline- specific
PIWI- interacting RNAs (piRNA). However, their mechanistic roles in gametogenesis and human
infertility are largely uncharacterized. The goal of this study is to elucidate the role of
small RNA pathways in the events that give rise to viable euploid gametes. Four projects and
three cores are included in this study.
and diverse roles in germ cell development and quality, including X/Y silencing during
meiosis, gene regulation, DNA damage responses, and protection of the genome against
transposable elements. Indeed, mammalian germ cells are known to harbor multiple small RNA
species, including small interfering RNAs (siRNA), microRNAs (miRNA), and germline- specific
PIWI- interacting RNAs (piRNA). However, their mechanistic roles in gametogenesis and human
infertility are largely uncharacterized. The goal of this study is to elucidate the role of
small RNA pathways in the events that give rise to viable euploid gametes. Four projects and
three cores are included in this study.
Project 2 (PI: Dr. Darius Paduch): Role of Small RNAs in male infertility. The leading
hypothesis of this project is based on extensive preliminary results obtained by this group
showing that 70% of miRNA expressed from human testis are highly conserved in humans and
rodents. The investigators hypothesize that differentially expressed miRNAs in men with
infertility lead to changes in levels of target messenger RNAs (mRNAs) involved in key
regulatory pathways in cell biology. The results of this project will lead to better
understanding of miRNAs' role in male reproduction and have strong potential to enable the
development of new miRNA-based or miRNA-regulating therapies. This project will help to
develop new transgenic animals to study miRNA in vivo with implications not only for
infertility, but also biology of testicular cancer. Derived RNA based therapies have the
potential to be less invasive, less toxic, and more effective in treating these serious and
increasingly prevalent conditions.
Core A (PI: Dr. Paula E. Cohen): Administration Core. The main objective of the
Administrative Core (Core A) is to provide a structure and support mechanism to the entire
Center for Reproductive Genomics (CRG). The Admin core will facilitate interactions across
the Ithaca and Manhattan campuses of Cornell University, will encourage research in small RNA
biology, both in reproductive medicine and across clinical disciplines, and will promote
strong training in reproductive medicine that encourages a translational focus. In general,
the Admin core will focus efforts on three major philosophies: translational and innovative
research, teaching, and outreach.
Core B (PI: Dr. Andrew Grimson): RNA Sequencing Core. The main objective of the RNA
Sequencing Core (RSC) is to provide users with efficient and high quality access to
cutting-edge sequencing technologies. These sequencing technologies will be used by all
members of this P50-proposal, and made available to other P50-centers. Importantly, all
members of this P50 are relying on access to these technologies to achieve their project
goals. By centralizing sequencing at the RSC, sequencing will be performed at a lower cost
and with greater efficiency that would be possible for individual users.
Core C (PI: Dr. Peter Schlegel): Outreach Core 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.
hypothesis of this project is based on extensive preliminary results obtained by this group
showing that 70% of miRNA expressed from human testis are highly conserved in humans and
rodents. The investigators hypothesize that differentially expressed miRNAs in men with
infertility lead to changes in levels of target messenger RNAs (mRNAs) involved in key
regulatory pathways in cell biology. The results of this project will lead to better
understanding of miRNAs' role in male reproduction and have strong potential to enable the
development of new miRNA-based or miRNA-regulating therapies. This project will help to
develop new transgenic animals to study miRNA in vivo with implications not only for
infertility, but also biology of testicular cancer. Derived RNA based therapies have the
potential to be less invasive, less toxic, and more effective in treating these serious and
increasingly prevalent conditions.
Core A (PI: Dr. Paula E. Cohen): Administration Core. The main objective of the
Administrative Core (Core A) is to provide a structure and support mechanism to the entire
Center for Reproductive Genomics (CRG). The Admin core will facilitate interactions across
the Ithaca and Manhattan campuses of Cornell University, will encourage research in small RNA
biology, both in reproductive medicine and across clinical disciplines, and will promote
strong training in reproductive medicine that encourages a translational focus. In general,
the Admin core will focus efforts on three major philosophies: translational and innovative
research, teaching, and outreach.
Core B (PI: Dr. Andrew Grimson): RNA Sequencing Core. The main objective of the RNA
Sequencing Core (RSC) is to provide users with efficient and high quality access to
cutting-edge sequencing technologies. These sequencing technologies will be used by all
members of this P50-proposal, and made available to other P50-centers. Importantly, all
members of this P50 are relying on access to these technologies to achieve their project
goals. By centralizing sequencing at the RSC, sequencing will be performed at a lower cost
and with greater efficiency that would be possible for individual users.
Core C (PI: Dr. Peter Schlegel): Outreach Core 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.
Inclusion Criteria:
- Men between the ages of 18-90 who have testicular cancer and underwent surgery at
Weill Cornell Medicine.
Exclusion Criteria:
- Women, men outside of the age parameters
We found this trial at
1
site
New York, New York 10065
Principal Investigator: Darius A Paduch, M.D., Ph.D.
Phone: 212-746-5706
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