Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.


The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.


Export to Word (
Principal Investigator: Sparks, Nicole Renee
Institute Receiving Award University Of California-Irvine
Location Irvine, CA
Grant Number R00ES032486
Funding Organization National Institute of Environmental Health Sciences
Award Funding Period 15 Dec 2020 to 31 Aug 2025
DESCRIPTION (provided by applicant): Every 4.5 minutes, a baby is born with a birth defect in the United States. Skeletal defects of the bony skeleton have been associated with environmental chemical exposure in utero. Our lab has shown that proper development of osteoblasts, the bone forming cells, depends on tight regulation of bone-specific genes. We developed a human embryonic stem cell (hESC) system where toxicant-induced differential gene expression perturbed osteoblast differentiation. MicroRNAs (miRNAs) are small non-coding RNAs that epigenetically regulate gene expression and are actors of skeletal development. There is no knowledge whether miRNAs adversely respond to environmental agents to result in skeletal malformations. In this proposal, I hypothesize that toxicant-induced miRNA changes play a critical role in the manifestation of skeletal birth defects. MiRNA profiling on differentiating hESCs previously identified 10 miRNAs downregulated stemming from chemical exposure that repressed osteoblast differentiation. I propose to 1) validate the functional role of candidate miRNAs during osteogenesis (K99); 2) investigate whether the functional effects of the candidate miRNAs are replicated in vivo (K99); 3) determine the mRNA target genes and signaling pathways affected by the candidate miRNAs (K99); and 4) investigate whether miRNA dysregulation is facilitated through epigenetic machinery that represses miRNA expression (R00). The proposed aims will significantly impact the understanding of environmentally induced epigenetic toxicity during skeletal development. Mentors Drs. Martin Riccomagno (survival surgeries and genome engineering) and Nicole zur Nieden (hESCs, miRNAs and genome engineering) will aid in my training for successful completion of the proposed aims and becoming an independent principal investigator. Additional support will come from Drs. Martin Garcia-Castro (molecular cytogenetic techniques) and Patrick Allard (epigenetic toxicology). The career development plan includes training to enhance my research skills, including Next Generation Sequencing, bioinformatics, in utero electroporation, and in vivo skeletal analysis, as well as scholarly skills and professional development, including but not limited to science communication, writing, mentoring, and management skills. The planned training and research will facilitate the transition to independency and success as a principal investigator.
Science Code(s)/Area of Science(s) Primary: 57 - Bone and Cartilage
Secondary: 03 - Carcinogenesis/Cell Transformation
Publications See publications associated with this Grant.
Program Officer Thaddeus Schug
to Top