# Mechanisms of Sonic Hedgehog Signal Transduction

> **NIH NIH R35** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2024 · $500,500

## Abstract

PROJECT SUMMARY
The evolutionarily conserved Sonic Hedgehog (SHH) signaling pathway governs tissue morphogenesis during
development and contributes to tissue homeostasis in adults. Alteration of pathway activity drives
developmental disorders including Holoprosencephaly (HPE), Pallister-Hall Syndrome and Basal Cell Nevus
syndrome. Inappropriate activation of signaling post-developmentally is frequently associated with cancer,
being causative in basal cell carcinoma and medulloblastoma, and implicated as a survival factor in a range of
additional tumor types. As such, there is significant interest and therapeutic potential in defining the
mechanisms governing SHH pathway activity. My laboratory’s long-term goal is to define the regulatory
processes governing SHH pathway activity during development and use this knowledge to identify
opportunities for targeting inappropriate SHH signaling in disease. Over the next 5 years, we will continue to
work toward this goal by interrogating and defining the molecular mechanisms controlling pivotal regulatory
steps of the SHH signal transduction cascade. We are focused on elucidating 1) how SHH ligand release and
transport are controlled to establish a morphogen gradient, 2) how SMO activation is controlled and how it
coordinates its activity with other G protein coupled receptors at the primary cilium, and 3) how GLI
transcriptional activator induction and destabilization are coordinated to assure an appropriate transcriptional
response.

## Key facts

- **NIH application ID:** 10904650
- **Project number:** 5R35GM122546-07
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Stacey Kathryn Ogden
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $500,500
- **Award type:** 5
- **Project period:** 2017-08-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10904650

## Citation

> US National Institutes of Health, RePORTER application 10904650, Mechanisms of Sonic Hedgehog Signal Transduction (5R35GM122546-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10904650. Licensed CC0.

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