# Investigating the Role of Heterotrimeric G Proteins in Craniofacial Development and Auriculocondylar Syndrome

> **NIH NIH K99** · UNIVERSITY OF COLORADO DENVER · 2024 · $133,134

## Abstract

My long-term career goal is to become a productive and impactful independent investigator in the field of
craniofacial development, by conducting cutting-edge, multidisciplinary research to better understand the
genetic, molecular, and cellular mechanisms of craniofacial development and disorders. The goal of my
research is to improve human health by elucidating disease mechanisms and contributing towards efforts to
develop therapeutic strategies. This application will provide the framework to achieve these goals through a
coordinated career development plan that utilizes the expertise of a diverse team of mentors and advisors, and
the supplemental training opportunities provided by coursework and conferences. These factors are woven into
my research strategy addressing important questions in craniofacial development and mechanisms of
disorders and expands my training into new areas that are essential for my transition to an independent
researcher career. This includes becoming an expert in genetic and transgenic models of zebrafish, genome-
wide sequencing approaches like single cell ATAC-seq and ChIP-seq, and human craniofacial anatomy. My
mentor team, led by Drs. Clouthier and Nichols, will provide valuable guidance throughout the training plan,
including the academic job search and career transition process. Moreover, this training will be carried out at in
a stellar research environment in the Department of Craniofacial Biology, and the University of Colorado
Anschutz Medical Campus, that collectively have the resources, core facilities, and faculty members needed to
ensure the success of this career development plan. This application will address important yet unstudied
events in intracellular signaling downstream of the Endothelin receptor type A (EDNRA) that establishes
patterning domains along the dorsal-ventral (D-V) axis of pharyngeal arch 1 (PA1). EDNRA signaling is
required for lower jaw development and is disrupted in a human craniofacial disorder called Auriculocondylar
syndrome (ARCND). EDNRA can signal through all four classes of G proteins, though how dynamic use of
different G proteins by EDNRA to pattern different domains of PA1 is unknown and extremely difficult to study.
This proposal will use three aims to test the hypothesis that the Gq/11 class exclusively patterns the
intermediate domain of PA1, and that Gq/11 regulates patterning gene expression by inducing
genome-wide changes to chromatin accessibility. Aim 1 will use genetic and transgenic approaches to
determine whether Gq/11 is necessary and sufficient for intermediate domain patterning. Aim 2 will use
multimodal single-cell analysis to define cis-regulatory elements and gene regulatory networks controlled by
Gq/11. Aim 3 will use zebrafish models of ARCND to understand how disease alleles impact EDNRA-Gq/11
signaling. Furthermore, this information will be used to better understand human cases of ARCND.
Collectively, this comprehensive research training and career d...

## Key facts

- **NIH application ID:** 10843241
- **Project number:** 5K99DE032428-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Stanley Michinobu Kanai
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $133,134
- **Award type:** 5
- **Project period:** 2023-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10843241

## Citation

> US National Institutes of Health, RePORTER application 10843241, Investigating the Role of Heterotrimeric G Proteins in Craniofacial Development and Auriculocondylar Syndrome (5K99DE032428-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10843241. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*