# Autophagy-mediated defense against inflammation and cancer

> **NIH NIH R01** · WISTAR INSTITUTE · 2021 · $415,844

## Abstract

Project Summary
Mounting evidence from our laboratory and others suggests that a lysosomal degradation pathway, called
autophagy, plays a central role in orchestrating inflammation and cancer biology. Recently, our laboratory
generated UVRAG (UV irradiation resistance associated gene) mutant mice that show normal levels of basal
autophagy but are deficient in stimulus-induced autophagy. With this mouse model, we demonstrate that
autophagy dysregulation could exacerbate inflammation and promote spontaneous cancers. However, major
gaps still exist in our understanding of intricate relationship between autophagy, inflammation and cancer,
including 1) what are the mechanisms by which inadequate autophagy perpetuates inflammasome response
and drives inflammation-associated pathologies? and 2) how does basal autophagy suppression affect tissue
homeostasis and promote cancer susceptibility? This project will fill these gaps by focusing on two Specific
Aims, including 1) investigating molecular mechanism of autophagy dysfunction on inflammatory signaling and
inflammation-associated pathologies; and 2) identifying molecular mechanism of autophagy inhibition in Wnt/b-
catenin signaling activation and spontaneous tumorigenesis. These aims will be addressed using
multidisciplinary innovative approaches that integrate state-of-the-art genetic, biochemistry, single cell analysis,
and physiological assays in cells, 3D organoid culture, and mice with targeted mutations in genes related to
UVRAG function and autophagy deregulation. Together, we anticipate that these studies will elucidate the
mechanisms underlying the intricate dialog between imbalance of autophagy, uncontrolled inflammation, and
spontaneous tumorigenesis, thereby providing important new insights into the functional repertoire of
autophagy and facilitating the development of much-needed new strategies for the treatment of inflammatory
pathologies and cancer, particularly those associated with autophagy defects.

## Key facts

- **NIH application ID:** 10296149
- **Project number:** 2R01CA140964-12A1
- **Recipient organization:** WISTAR INSTITUTE
- **Principal Investigator:** Chengyu Liang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $415,844
- **Award type:** 2
- **Project period:** 2009-09-21 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10296149

## Citation

> US National Institutes of Health, RePORTER application 10296149, Autophagy-mediated defense against inflammation and cancer (2R01CA140964-12A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10296149. Licensed CC0.

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