# Mechanisms of RNA and Protein Dysregulations in ALS/FTD Associated with FUS and Ubiquilin 2

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $417,888

## Abstract

Project Summary
Neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal
dementia (FTD) are increasing public health challenges, for which effective treatment is still
lacking. At least two major themes that have emerged from the studies of ALS/FTD, concerning
etiology related to both RNA metabolism and protein homeostasis. However, the mechanisms of
RNA and protein homeostasis are not completely independent. UBQLN2 is a protein quality
control factor that has been linked to ALS/FTD. Mutations in UBQLN2 have been linked to
ALS/FTD, and UBQLN2 immunoreactivity is found in ALS/FTD and other neurodegenerative
conditions. We have identified a role for UBQLN2 in antagonizing the aberrant phase transition
and stress granule formation of mutant FUS, behaviors that potentially disrupt the RNA-
processing functions of FUS and lead to neurodegeneration. The induced pluripotent stem cells
(iPSC)-derived models have become instrumental experimental systems for study the
pathological mechanisms and therapeutic interventions for neurodegenerative diseases
including Alzheimer’s disease and related dementias (ADRD). Here we will characterize iPSC
lines that harbor ADRD-related mutations in order to develop better ADRD disease models. The
project is aimed at deep quality control and molecular phenotyping of the iPSC lines to generate
predictable and reliable models. The outcome of the studies will not only provide clinically
relevant models for this form of neurodegeneration diseases such as ALS/FTD but also
generate insights into the pathogenic mechanisms as well as therapeutic applications for the
devasting diseases.

## Key facts

- **NIH application ID:** 10401555
- **Project number:** 3R01NS110098-03S1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Jiou Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $417,888
- **Award type:** 3
- **Project period:** 2019-02-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401555

## Citation

> US National Institutes of Health, RePORTER application 10401555, Mechanisms of RNA and Protein Dysregulations in ALS/FTD Associated with FUS and Ubiquilin 2 (3R01NS110098-03S1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10401555. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*