# POST-TRANSCRIPTIONAL REGULATION OF CELL FATE IN EARLY MAMMALIAN DEVELOPMENT

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $142,401

## Abstract

Post-transcriptional regulation by RNA-binding proteins (RBPs) and microRNAs (miRNAs) orchestrate diverse
molecular and cellular mechanisms that pattern early mammalian development from embryonic stem cells
(ESCs) through gastrulation and lineage commitment. The RBPs Ago2 (Argonaute-2) and IRP (iron regulatory
proteins) respectively coordinate miRNA-mediated regulation and cellular iron regulation, mechanisms essential
for the proper execution of early embryonic development. In human development, cellular iron regulation is
important for non-hematopoietic tissue development, including neurogenesis and gut development, in addition
to erythropoiesis. However, the identities and functional roles of miRNA- and IRP-bound targets in cell fate
decisions during early embryonic development are largely unknown. A comprehensive understanding of the
dynamic relationships of IRPs, miRNAs, and their functional targets during this critical developmental window is
needed and can provide a roadmap for functional rewiring in stem/progenitor cell-based regenerative therapies.
The central hypothesis of this proposal is that IRP and miRNAs function cooperatively and dynamically on targets
that are important regulators of cell fate transitions during mammalian development. As a molecular biologist
and pathologist, my long-term goal is to understand and use these integrated pathways of post-transcriptional
control to devise new tools and approaches for functional rewiring in stem/progenitor cell-based regenerative
therapies. The objective of this project is to dissect the specific roles of post-transcriptional regulation by miRNAs
and IRPs on cell fate decisions in early mammalian development and to build platforms to model cellular iron
throughout early mammalian development. This project objective will be achieved by 1) determining the impact
of IRP and miR-290-mediated regulation on Profilin-2, a known regulator of ESC differentiation, 2) identifying
and functionally dissecting the global network of bound IRP and miRNA targets, and 3) developing biosensor
platforms that model cellular iron utilization in vitro and in vivo during early embryonic development. The
proposed studies are the core components of the Mentored Clinical Scientist Development Award (K08) for Dr.
Carolyn Sangokoya. Dr. Sangokoya is a board-certified Anatomic Pathologist with subspeciality expertise in
surgical and gastrointestinal/hepatobiliary pathology. This proposal encompasses a five-year plan to address
gaps in specific research and professional skills as she transitions to independence as a physician-scientist. This
grant is a training vehicle for Dr. Sangokoya to 1) build knowledge in statistical methods for functional genomics,
2) learn and expand technical skills in generating mouse models, 3) perform single-cell RNA-sequencing studies,
and 4) develop professional scientific leadership and lab management skills in transition to leading a successful
laboratory. To achieve these goals, Dr...

## Key facts

- **NIH application ID:** 10810771
- **Project number:** 5K08HD105017-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** CAROLYN O SANGOKOYA
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $142,401
- **Award type:** 5
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10810771

## Citation

> US National Institutes of Health, RePORTER application 10810771, POST-TRANSCRIPTIONAL REGULATION OF CELL FATE IN EARLY MAMMALIAN DEVELOPMENT (5K08HD105017-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10810771. Licensed CC0.

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