# Single-Cell Transcriptional and Epigenomic Dissection to Identify Therapeutic Targets for ALS and FTD

> **NIH NIH R56** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2020 · $753,520

## Abstract

Abstract
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are devastating and fatal
neurodegenerative diseases that strike middle-aged adults just as they reach full familial, financial and career
potential. Initially thought to be quite distinct, ALS and FTD are now recognized to share many clinical,
pathological, and genetic signatures, but the mechanistic basis of their shared and distinct circuitry remains
unknown at the molecular level. Genome-wide association studies (GWAS) have uncovered multiple common
weak-effect variants, but the vast majority are non-coding, making it difficult to identify their target genes and
the cell types where they act. To address this challenge, we systematically profile the transcriptional and
epigenomic alterations of ALS and FTD patients at single-cell resolution using post-mortem brain samples from
ALS and FTLD patients (Aim 1). We integrate the resulting datasets to study the link between genetic,
epigenomic, transcriptional, and cellular signatures of ALS and FTD, and to study the common and distinct
genes and pathways altered in each, to predict new therapeutic targets (Aim 2). We validate the molecular and
cellular effects of these targets using high-throughput directed perturbation experiments, and disseminate all
our results to the community (Aim 3). The resulting datasets, analyses, and validated targets will provide an
invaluable resource to understand the mechanisms of action of ALS and FTD, and the common and unique
circuitry towards new therapeutic targets.

## Key facts

- **NIH application ID:** 10238537
- **Project number:** 1R56AG067151-01
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Manolis Kellis
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $753,520
- **Award type:** 1
- **Project period:** 2020-09-04 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10238537

## Citation

> US National Institutes of Health, RePORTER application 10238537, Single-Cell Transcriptional and Epigenomic Dissection to Identify Therapeutic Targets for ALS and FTD (1R56AG067151-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10238537. Licensed CC0.

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