# Structural Mechanisms of Hedgehog Autoprocessing in Physiology and Disease

> **NIH NIH R01** · RENSSELAER POLYTECHNIC INSTITUTE · 2020 · $433,541

## Abstract

The Hedgehog (Hh) signaling pathway plays important roles in development and in cancer. The Hh ligand,
which activates the pathway, is derived from the autoprocessing of the Hh precursor protein. Hh
autoprocessing is at the very beginning of the Hh signaling pathway and likely plays crucial roles in both
physiology and disease. However, the basic mechanisms of Hh autoprocessing and its role in diseases are
poorly understood. Using an interdisciplinary approach, we will define the catalytic mechanism of Hh
autoprocessing with atomic resolution and study two novel roles for Hh autoprocessing in prostate cancer. We
will first define the catalytic mechanism of Hh autoprocessing with solution NMR; we will then study a new
mechanism of tumorigenesis involving zinc deficiency and Hh activation in prostate cancer; lastly we will
establish Hh autoprocessing of cancer drugs as a novel means of drug resistance in prostate cancer.

## Key facts

- **NIH application ID:** 9830627
- **Project number:** 5R01CA206592-04
- **Recipient organization:** RENSSELAER POLYTECHNIC INSTITUTE
- **Principal Investigator:** Brian Patrick Callahan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $433,541
- **Award type:** 5
- **Project period:** 2016-12-15 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9830627

## Citation

> US National Institutes of Health, RePORTER application 9830627, Structural Mechanisms of Hedgehog Autoprocessing in Physiology and Disease (5R01CA206592-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9830627. Licensed CC0.

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