# DNA methylation in the development of multiple sclerosis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $658,512

## Abstract

Summary
This application is concerned with the study of epigenetics events affecting multiple sclerosis (MS) risk
and progression. We present preliminary results consistent with widespread differential
hypomethylation in peripheral CD19+ B cells at the time of diagnosis, posing a mechanistic link to the
clinical efficiency of anti-CD20 antibody treatment for this disease. We build on these results and
access to informative and diverse data- and sample-sets to propose in Specific Aim 1 the simultaneous
assessment of single-cell gene expression (scRNA-seq), chromatin accessibility (scATAC-seq), and
cell surface markers in paired cerebrospinal fluid (CSF) and peripheral blood mononuclear cells from
treatment naïve MS patients at the time of clinical onset and well matched controls, and link in Aim 2 to
the individuals’ DNA variance to develop global and cell-specific genetic burdens associated with
disease expression. In Aim 3 we connect the emerging epigenetic and transcriptome signatures with
cell function using the Beacon® system optofluidic platform to visualize and assess cellular phenotypes
at the single-cell level. In Aim 4 we implement a targeted trimodal single-cell assay to describe the
epigenetic landscape of the principal MS susceptibility locus, the Major Histocompatibility Complex in
chromosome 6p21. By systematically integrating single cell chromatin states, DNA variance, and gene
expression data, we expect to gain important novel information about pathogenesis. Moreover, we will
identify cell-specific epigenetic signatures associated with MS clinical onset, potentially serving as
biomarkers of affectation status. The meticulous clinical follow up of study participants offers an
opportunity to assess their prognostic potential.

## Key facts

- **NIH application ID:** 10660209
- **Project number:** 1R01NS128277-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Jorge R. Oksenberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $658,512
- **Award type:** 1
- **Project period:** 2023-05-15 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10660209

## Citation

> US National Institutes of Health, RePORTER application 10660209, DNA methylation in the development of multiple sclerosis (1R01NS128277-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10660209. Licensed CC0.

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