# Accelerating Muscle Recovery in Critical Illness

> **NIH NIH K08** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2021 · $178,200

## Abstract

PROJECT SUMMARY
 The candidate, D. Clark Files, MD, is a critical care physician-scientist seeking a K08 Mentored Clinical
Scientist Research Career Development Award to develop and apply his skills to assess the mechanisms
underlying skeletal muscle wasting in older patients experiencing a critical illness, such as acute respiratory
distress syndrome (ARDS) or sepsis. Dr. Files' career goal is to become an independent translational research
leader focused on discovering mechanisms and developing therapies to reduce the morbidity and mortality of
critical illnesses in older patients. The strategies outlined in this proposal provide the foundation to accomplish
this goal.
 Skeletal muscle weakness has recently been identified as a major contributor to death and long-term
disability from ARDS and sepsis. Older patients have increased mortality and muscle weakness from these
conditions compared to younger patients. In order to understand these age-related differences in outcomes,
the candidate developed mouse models of ARDS and sepsis in older animals, optimized for studying muscle
function. In these models, older critically ill mice exhibit increased mortality and muscle wasting coupled to
increased muscle proteolysis and impaired fatty acid metabolism. The goals of the studies outlined in the
Research Plan (RP) are to identify mechanisms underlying these age-related differences and to attenuate
muscle wasting in old critically ill mice through manipulation of the ubiquitin proteasome (UPP) and fatty acid
oxidation pathways in skeletal muscle. To facilitate translation of these mechanisms into humans, the
candidate will evaluate key mediators of these pathways in the muscles of patients with critical illness.
 The Career Development Plan (CDP) of this proposal outlines a detailed strategy for educational and
experiential learning in the areas of muscle physiology and biology, metabolism, clinical research and
leadership. The mentorship team, with individual strengths in each of these areas, seeks to facilitate
development of Dr. Files' basic science skills in a translational context and provide the foundations for future
clinical research to become an independent investigator in critical care research. Key institutional resources
include the Wake Forest Critical Illness Injury and Recovery Research Center, the Wake Forest Claude D.
Pepper Older Americans Independence Center, and the Wake Forest Bioenergetics Core Facility.
 In summary, execution of the RP and the CDP of this proposal will fill a gap in knowledge about the
physical function impairment associated with post-intensive care syndrome and will position Dr. Files to
become a leader in this important area of emerging research.

## Key facts

- **NIH application ID:** 10168565
- **Project number:** 5K08GM123322-04
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Daniel Clark Files
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $178,200
- **Award type:** 5
- **Project period:** 2018-06-10 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10168565

## Citation

> US National Institutes of Health, RePORTER application 10168565, Accelerating Muscle Recovery in Critical Illness (5K08GM123322-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10168565. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*