# Role of mitophagy in age-related respiratory and vascular diseases

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $585,000

## Abstract

PROJECT SUMMARY/ABSTRACT
The overarching theme of my research program is to understand how innate immunity enhances age-
associated cardiovascular and pulmonary diseases. As a physician scientist, I have investigated innate
immunity in different diseases for 20 years. After making several seminal findings on the role of Toll-like
receptors (TLRs), key innate immune receptors, in organ transplantation, I applied my knowledge of innate
immunity to the studies of age-related diseases. My laboratory has made several groundbreaking findings as to
how inflammation promotes diseases during aging, specifically: i) systemic viral infections; ii) influenza lung
infection; iii) vascular diseases; and iv) organ transplant rejection. Our central theme in this proposal is that
alterations in mitophagy, a physiological process to remove damaged mitochondria, underpins the spread of
influenza lung infection and the progression of vascular diseases. We hypothesize that during influenza viral
infection the virus “hijacks” mitophagy to enhance viral spread, reduce anti-viral immunity and further weaken
host defense. During chronic vascular inflammation, we hypothesize that impaired mitophagy leads to the
accumulation of mitochondrial DNA, which activates innate immunity to promote diseases, such as
atherosclerosis, hypertension and abdominal aortic aneurysms (AAA). Based on our prior publications and
novel preliminary data, we will pursue two broad goals in this proposal. The first goal will elucidate the role of
mitophagy during influenza viral infection using novel mitophagy reporter mice and transgenic mice in which
key mitophagy proteins have been conditionally deleted. In our second goal, we will use our novel mice to
elucidate the dynamics of mitophagy and its requirement during atherosclerosis, hypertension and then AAA
development. In both goals, we will leverage key biorepositories at The University of Michigan to translate our
findings to humans. This award mechanism will allow us to reveal novel pathways by which mitophagy impacts
both influenza infection and vascular diseases, such as atherogenesis and AAA. By translating our findings to
humans over the course of this award, our research program has the potential to develop novel therapies to
improve the outcomes of respiratory viral infections and vascular diseases, particularly in the elderly.

## Key facts

- **NIH application ID:** 10103978
- **Project number:** 1R35HL155169-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Daniel Robert Goldstein
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $585,000
- **Award type:** 1
- **Project period:** 2021-01-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10103978

## Citation

> US National Institutes of Health, RePORTER application 10103978, Role of mitophagy in age-related respiratory and vascular diseases (1R35HL155169-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10103978. Licensed CC0.

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