# Do Changes in Thiol Metabolism Mediate Osteoarthritis Progression?

> **NIH NIH R00** · UNIVERSITY OF IOWA · 2020 · $249,000

## Abstract

This career development project is focused on orthopedic training and conducting novel research into the
role of thiol metabolism during chronic oxidative stress after mechanical injury to establish an independent
line of research. This will be done under the guidance of: primary mentor, Dr. James Martin, an expert in
orthopedic cell biology with over 30 years’ experience in research and training; co-mentor for redox biology,
Dr. Douglas Spitz, an expert in redox biology with 30 years of continuous independent NIH funding and
training experience including an NIH T32 and several K-award mentorships; and clinical co-mentor, Dr.
Larry Marsh, a world class trauma surgeon and clinical researcher with experience training clinical and
basic scientists. These mentors will guide the acquisition of preliminary data to characterize chondrocyte
thiol metabolism and redox signaling, the search and negotiation for a tenure track position, the execution
of the R00 research into thiol metabolism after injury, and final R01 composition to establish independence.
The training goal of the K99 phase of this project is to provide critical knowledge and experience for
operation as an independent orthopedic researcher via incorporation into resident training. Resident
conferences will be attended including no fewer than three days a week, 1-2 hours each day. The
distinguished University of Iowa Department of Orthopedics and Rehabilitation provides a powerful
research environment for pursuit of research goals during the K99 phase, highlighted by large animal
models of orthopedic disease. Concurrent with their funded projects and using the same animals, the redox
status of intracellular thiols including glutathione and mitochondrial thioredoxin/peroxiredoxin, NRF2/Bach-1
interplay, GPx4 content, and mitochondrial redox function during disease development after intraarticular
fracture will be measured. These endpoints have not been explored as a unified pathway, and have not
been described in these disease settings. Observing these pathways over three different time points
corresponding to early, intermediate, and late stages of disease in a large animal model will allow for a
comprehensive understanding of the status of intracellular thiols over time. Taken together with the clinical
training described, this will result in an enhanced orthopedic skill set, and development of novel research
ideas in well characterized orthopedic models. Detailed description of thiol redox responses during disease
will enable logical design of an adeno-associated virus seeking to disrupt thiol metabolism similar to
chronic orthopedic disease processes. As the R00 phase commences, data from the K99 phase will guide
construction and characterization of the viral tool described. Once this tool has been validated, it will be
applied in a rabbit model of post-traumatic injury and complimented with a transgenic mouse resistant to
oxidative stress. By comparing responses to injury from control ra...

## Key facts

- **NIH application ID:** 9988157
- **Project number:** 5R00AR070914-04
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Mitchell Carl Coleman
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2018-09-14 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988157

## Citation

> US National Institutes of Health, RePORTER application 9988157, Do Changes in Thiol Metabolism Mediate Osteoarthritis Progression? (5R00AR070914-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9988157. Licensed CC0.

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