# Tools to evaluate POP2 as a regulator of arthritis

> **NIH NIH R03** · ALBANY MEDICAL COLLEGE · 2020 · $81,292

## Abstract

Project Summary:
Inflammation underlies the disabling manifestations and co-morbidities of rheumatoid arthritis (RA). Genetic
differences in the regulation of inflammatory signaling between individuals are highly relevant and significant as
such differences likely determine those individuals that will progress to RA, the severity of their disease, and
even influence the treatment options that will be palliative. Much of our understanding of the pathophysiology
of RA is based in part on animal models. However, recent work demonstrates that humans posses seven
genes coding Pyrin-only and CARD-only proteins (POPs and COPs) that limit NF-kB signaling and
infammasome activation pathways, events critical for elaboration of the cytokines mediating inflammation. We
have identified an allele of POP2 associated with severe, and likely treatment resistant RA. Evaluating the
function of this RA-associated allele in vivo and in vitro will help reveal the immunological and molecular basis
for the association and provide insight into why some RA patients develop severe RA resistant to otherwise
effective treatment with sophisticated biologics targeting TNF and IL-6. Such knowledge could help guide
clinical decision making and advance efforts to identify new therapeutic modalities. This application proposes
a transgenic mouse model and cellular tools to investigate the nature of the POP2 allele associated with RA.
These tools are a necessary first step towards further investigation of the function of POP2 in RA disease.

## Key facts

- **NIH application ID:** 9979151
- **Project number:** 1R03AI146596-01A1
- **Recipient organization:** ALBANY MEDICAL COLLEGE
- **Principal Investigator:** JONATHAN A HARTON
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $81,292
- **Award type:** 1
- **Project period:** 2020-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979151

## Citation

> US National Institutes of Health, RePORTER application 9979151, Tools to evaluate POP2 as a regulator of arthritis (1R03AI146596-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9979151. Licensed CC0.

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