# Chemical probes to decipher PAD biology

> **NIH NIH R35** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2021 · $938,000

## Abstract

PROJECT SUMMARY
 Protein citrullination is increased in inflammatory disease and cancer, and the evidence indicates that this
post-translational modification is a major contributor to disease pathogenesis. In fact, inhibition of protein
citrullination decreases disease severity in animal models of rheumatoid arthritis, ulcerative colitis, nerve
damage, and cancer. Thus, the Protein Arginine Deiminases (PADs), which catalyze this PTM, represent novel
therapeutic targets.
 The overall goal of this renewal application is to investigate how protein citrullination impacts human cell
signaling. Specific questions to be addressed include: (1) What proteins are citrullinated?; (2) How does
citrullination affect activity?; (3) Does citrullination impact proteolytic events? and (4) Can we generate
isozyme specific inhibitors? Answers to these questions will be obtained by (1) developing chemoproteomic
platforms to identify citrullination events; (2) developing and using a genetic code expansion platform to
evaluate the functional consequences of individual citrullination events; and (3) developing chemical probes
and isozyme selective PAD inhibitors to modulate cellular citrullination levels. By addressing each of these
questions, the PI expects to provide a holistic understanding for how the PADs contribute to human biology.
 Given the outstanding track record of the PI and his leadership position in the PAD field, combined with his
strong network of collaborators, this project will provide new insights and sorely needed research tools to the
scientific community. Key outcomes include the discovery of new PAD biology, which is predicted to have
major translational impacts on autoimmunity and cancer.

## Key facts

- **NIH application ID:** 10086148
- **Project number:** 2R35GM118112-06
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Paul R Thompson
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $938,000
- **Award type:** 2
- **Project period:** 2016-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10086148

## Citation

> US National Institutes of Health, RePORTER application 10086148, Chemical probes to decipher PAD biology (2R35GM118112-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10086148. Licensed CC0.

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