# High-spatial-resolution multi-omics sequencing of brain lesions in multiple sclerosis

> **NIH NIH DP2** · UNIVERSITY OF PENNSYLVANIA · 2024 · $465,818

## Abstract

Project Summary
Multiple sclerosis (MS) is a neuroinflammatory autoimmune disease of the CNS that results in demyelination,
axonal injury, and neuronal loss. Abnormal immune responses involving the trafficking of peripherally activated
immune cells into the CNS are major drivers of inflammatory disease activity in relapsing multiple sclerosis, as
underscored by the success of immune-targeting therapies. By contrast, the biology of non-relapsing
progressive disease is thought to involve CNS-compartmentalized inflammation and degenerative disease
mechanisms, which remains more refractory to therapy, due in part to the complexity of gene regulatory network
coupled with cell-type-specific mechanisms of MS lesion progression. What types or subtypes of cells are
affected by this process and their spatial heterogeneity in the tissue context as well as how these cells impact
the tissue environments remain poorly understood, which precludes the development of strategies to target
these cells to improve healthspan/lifespan or harnessing these cells or secreted factors to promote tissue
remodeling and repair, highlighting a pressing need for tools to map cells and the surround environments in the
tissues lesion and generate biomarkers to define spatial and phenotypic heterogeneity. This project aims to
develop novel molecular barcoding scheme and downstream biochemistry in combination with novel
microdevices for spatial multi-omics that allows simultaneous profiling of multi epigenomic modalities, whole
transcriptome, and a panel of proteins at tissue scale and cellular level in a spatially resolved manner. We will
apply the spatial multi-omics to map human brain tissue dissected from the edge of demyelinated white matter
MS lesions at different stages of inflammation as well as the demyelinated lesion core, the white matter
periplaque and normal white matter from neurologically healthy brains. Spatial omics data will be integrated with
single-cell data to identify signatures of different affected cells and perform the tissue neighborhood analysis to
define the cellular composition and molecular signatures in MS lesions. The expected outcomes and the major
contributions include: (1) Fundamental knowledge on diverse cell types and their epigenomic, transcriptional
and phenotypic (protein) characteristics in the context of 3D tissue organization in the MS brain lesions and (2)
Offer the possibility of testing new therapeutic approaches for MS that are not targeted by currently approved
treatments. The resulting data will lead to a better understanding of the relationship between tissue organization,
function, and gene regulatory networks in MS.

## Key facts

- **NIH application ID:** 10908636
- **Project number:** 5DP2AI177913-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Yanxiang Deng
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $465,818
- **Award type:** 5
- **Project period:** 2023-08-16 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10908636

## Citation

> US National Institutes of Health, RePORTER application 10908636, High-spatial-resolution multi-omics sequencing of brain lesions in multiple sclerosis (5DP2AI177913-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10908636. Licensed CC0.

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