# Transcriptional Checkpoints Of Autoimmune Encephalomyelitis

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $499,613

## Abstract

The overall objective of this research proposal is to elucidate a new pathological mechanism
underlying autoimmune diseases such as multiple sclerosis (MS) and to test a new class of
therapeutic compounds in models of MS. The proposal is inspired by two lines of recent
discoveries: (i) in humans, several genome-wide association studies independently established
that c-Rel, the lymphoid and myeloid member of the Rel/nuclear factor-kB (Rel/NF-kB) family, is
a risk factor for six autoimmune diseases including MS; (ii) in mice, c-Rel deficiency renders them
resistant to autoimmune encephalomyelitis, arthritis, and colitis while having limited impact on
infections. We therefore theorized that c-Rel is both a risk factor and a pathogenic factor for
human autoimmune diseases and that drugs targeting it should be effective for treating the
diseases. To test this theory, we have developed a new class of small molecules that specifically
inhibits c-Rel function by preventing its binding to DNA. In mice, these compounds are highly
effective in suppressing autoimmune responses and in ameliorating ongoing experimental
autoimmune encephalomyelitis, an animal model for MS. The specific goals of this proposal are
to elucidate the mechanism(s) through which c-Rel controls autoimmune encephalomyelitis, and
to test the theory that inhibition of c-Rel in both inflammatory and regulatory T cells is required to
cure autoimmune encephalomyelitis. Specifically, we will test the hypotheses that (i) c-Rel serves
as a transcriptional checkpoint of autoimmune encephalomyelitis; (ii) c-Rel controls autoimmune
encephalomyelitis in a cell- and gene-specific manner; and (iii) c-Rel blockade diminishes anti-
myelin immune responses of multiple sclerosis patients.

## Key facts

- **NIH application ID:** 9901072
- **Project number:** 1R01AI143676-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Youhai H Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $499,613
- **Award type:** 1
- **Project period:** 2019-12-20 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9901072

## Citation

> US National Institutes of Health, RePORTER application 9901072, Transcriptional Checkpoints Of Autoimmune Encephalomyelitis (1R01AI143676-01A1). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/9901072. Licensed CC0.

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