# Analysis of autophagy risk genes in inflammation and tissue homeostasis

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $547,355

## Abstract

PROJECT SUMMARY/ABSTRACT
Advancements in human genetics now poise the field to illuminate the pathophysiology of inflammatory
pathologies and infectious disease. Although the mechanisms of immune-mediated tissue homeostasis are
incompletely understood, genetic analyses of inflammatory disease and primary immunodeficiencies have
implicated shared proteins and pathways representing key immune checkpoints. Efforts to map the genetic
architecture of inflammatory bowel disease (IBD) have been particularly fruitful, leading to the discovery of
ATG16L1 T300A, which revealed the importance of autophagy in innate immunity. We have since shown that
the ATG16L1 T300A allele conspires with environmental triggers to induce several cell type-specific
phenotypes resulting in tissue dys-homeostasis and predisposition to inflammatory pathology. Thus,
mechanistic characterization of a pathogenic autophagy variant has provided fundamental insights into
mucosal immunity. The focus of this application is to understand how genetic perturbation of autophagy
checkpoints impacts inflammation control and tissue homeostasis in the context of mucosal immunity. Towards
this end, we propose to: (1) Define the role of autophagy checkpoints in intestinal inflammation, (2) Identify the
molecular mechanisms by which autophagy controls antigen presentation and tissue homeostasis, and (3)
Perform a comprehensive genetic dissection of the Inflammation-Autophagy link.

## Key facts

- **NIH application ID:** 9906895
- **Project number:** 5R01DK097485-07
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Ramnik J Xavier
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $547,355
- **Award type:** 5
- **Project period:** 2013-01-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9906895

## Citation

> US National Institutes of Health, RePORTER application 9906895, Analysis of autophagy risk genes in inflammation and tissue homeostasis (5R01DK097485-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9906895. Licensed CC0.

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