# High-throughput disease modeling to uncover shared and unique characteristics among neurodegenerative diseases

> **NIH NIH F31** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $45,520

## Abstract

Project Summary
 Neurodegenerative diseases (NDDs) present a large clinical and financial strain on the US healthcare
system. We currently lack effective FDA approved therapeutics that halt or reverse the course of disease for
many diseases in this class. Through modeling NDDs, we have begun to dissect the pathological impact of
genes and proteins implicated in NDD development. We have discovered perturbations of core cellular
processes such as protein folding and protein turnover are central to many NDDs. However, understandings of
mechanisms and pathways governing disease development awaits for many NDDs. To approach this challenge,
we propose a novel technology that using next generation DNA sequencing methods to examine multiple
neurodegenerative disease models within a single experiment, thereby increasing throughput and limiting inter-
experimental variation. To capture fundamental cellular perturbations imposed by each NDD model, we will
characterize each model’s response to a wide range of genetic perturbations. Subsequent analysis of these data
will reveal cellular pathways impacted by disease gene expression.
 We will apply this platform towards the study of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal
Dementia (FTD), which occur on a clinical spectrum. Mutations in different genes implicated in ALS/FTD can
bias patients towards either end of this spectrum. Additionally, there are many genetic variants implicated in
ALS/FTD which remain functionally uncharacterized. The genes implicated in ALS/FTD have been shown to play
a role in many cellular processes, including RNA metabolism, nucleocytoplasmic shuttling, and autophagosome
maturation. Our technological platform will allow us to capture the scope of cellular responses to dozens of genes
and alleles implicated in the development of ALS/FTD and also identify cellular targets for further study in human
neurons.
 The goals of this project are to: leverage our multiplexed disease modeling platform on a genome-wide
scale to identify of genes that enhance or ameliorate pathological consequences of genes implicated in ALS/FTD
(Aim 1), and to harness these findings to validate potential therapeutic leads in iPSC cortical neurons (Aim 2).

## Key facts

- **NIH application ID:** 10012778
- **Project number:** 5F31NS111851-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Samuel Jackson Resnick
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2019-09-15 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10012778

## Citation

> US National Institutes of Health, RePORTER application 10012778, High-throughput disease modeling to uncover shared and unique characteristics among neurodegenerative diseases (5F31NS111851-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10012778. Licensed CC0.

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