# Understanding How Ciliary Hedgehog Signaling Causes Medulloblastoma

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $177,124

## Abstract

PROJECT SUMMARY/ABSTRACT
The objective of this proposal is to train David R. Raleigh, MD, PhD, a candidate with an
excellent foundation for basic science research, to become an independent investigator of brain
tumor biology. The proposed research also aims to improve treatments for patients with
medulloblastoma, a common pediatric brain cancer. The proposed research addresses
limitations that have hindered therapeutic advancements for patients with medulloblastoma by
identifying novel, druggable targets that transduce oncogenic Hedgehog signaling via the
primary cilium. The candidate's central hypothesis is that the oxysterol synthase Hsd11β2
generates ciliary oxysterols that activate Hedgehog signaling and induce Cdk6 to drive
uncontrolled cell proliferation. This work will elucidate (1) how oncogenic Hh signaling is
transduced to cause cell growth; and (2) whether blocking this signaling is an effective
therapeutic strategy for Hh-associated medulloblastoma. Toward those goals, the following
specific aims are proposed: (1) determine how Hsd11β2 contributes to ciliary Hedgehog
signaling; and (2) define how Hedgehog signaling misactivates Cdk6 in medulloblastoma. The
candidate's training and research plan incorporates a combination of coursework, workshops,
mentoring, and hand-on research experience set in the outstanding academic environment of
UCSF, a center of excellence in medicine and research endowed with a well-integrated
community of clinicians and scientists. The candidate's mentor is Dr. Jeremy Reiter, a
recognized expert and pioneer in mouse genetic models and the molecular mechanisms of
vertebrate Hedgehog signaling through the primary cilium., both in development and in cancer.
The candidate's multidisciplinary advisory committee includes distinguished scientists with
expertise in all areas covered by the research strategy of this award. Successful completion of
the proposed research will produce compelling preclinical rationale for testing specific targeted
inhibitors in patients within biomarker-defined subsets of Hedgehog-associated
medulloblastoma. The intermediate-term goal is for the candidate to acquire the knowledge,
technical skill and expertise necessary to submit a successful R01 proposal. Long-term goals
are for the integrated, preclinical platform of Hedgehog-associated medulloblastoma developed
in this proposal to inform treatment decisions and improve survival of medulloblastoma patients.

## Key facts

- **NIH application ID:** 9966908
- **Project number:** 5K08CA212279-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** David R Raleigh
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $177,124
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9966908

## Citation

> US National Institutes of Health, RePORTER application 9966908, Understanding How Ciliary Hedgehog Signaling Causes Medulloblastoma (5K08CA212279-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9966908. Licensed CC0.

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