# Mechanistic study of Hedgehog signaling in the cilium

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, MERCED · 2022 · $384,752

## Abstract

PROJECT SUMMARY
Defects in Hedgehog (Hh) signaling is widely implicated in various birth defects and cancers. The
transduction of Hh signaling relies on the primary cilium, a miniature cell surface organelle viewed as
a signaling hub. Smoothened (Smo), the core switch of Hh signaling, translocates to the cilium to turn
on the Hh signaling. At the molecular level, the signaling mechanisms downstream of Smo are poorly
understood. This creates a large barrier to the development of pathway specific treatments for Hh-
related disorders. Our overarching goal is to elucidate mechanistic insights into Smo-related signaling
events during Hh transduction. To achieve this goal, we have established a proteomic flatform to
systematically identify Smo interacting proteins. Our pilot study in this flatform identified the catalytic
subunit of PKA as a Smo interacting proteins. We will innovate into the unknown areas of Hh signaling
by achieving two objectives: 1) systematically defining the Smo interacting proteins over the course of
Hh signal transduction with functional proteomics; 2) deciphering the mechanistic link between Smo
and PKA in the cilium during Hh signal transduction and Hh-related tumorigenesis. Our approach is
innovative because it employs cutting-edge molecular tools to answer a long-standing question in the
Hh pathway. Its significance is underlined by the expectation that it will shed light on long-standing
questions about Smo signaling in the Hh pathway, which will ultimately provide clues for the
development of new therapeutical methods for Hh-related cancers. This grant will give me opportunity
to engage students from underrepresented groups. My goal is to build solid research foundations for
these students for their future pursuit of careers in cancer field, helping to diversify the workforce in
basic study of cancers research.

## Key facts

- **NIH application ID:** 10527729
- **Project number:** 1R21CA274595-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, MERCED
- **Principal Investigator:** Xuecai Ge
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $384,752
- **Award type:** 1
- **Project period:** 2022-09-22 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10527729

## Citation

> US National Institutes of Health, RePORTER application 10527729, Mechanistic study of Hedgehog signaling in the cilium (1R21CA274595-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10527729. Licensed CC0.

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