# Investigating Dysregulation of Stress-related Ribonucleoprotein Granules and Functions of Associated RNA-binding Proteins in ALS/FTD

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $634,358

## Abstract

Project Summary
Protein and RNA homeostasis are two major themes in the study of neurodegenerative
diseases, as exemplified by the implications of many RNA-binding proteins (RBPs) in
amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other
neurodegenerative conditions. As a major pathology in ALS/FTD, protein misfolding and
aggregation, including those initiated by RBPs, manifest as a common thread among many
neurodegenerative diseases. Additionally, a large collection of genetic, biochemical, and
pathological evidence underscores the importance of RBPs in ALS/FTD and other
neurodegenerative disease and calls for a better understanding of the functions of these RBPs
and their associated cellular processes. A prominent feature of RBPs is their involvement in the
formation of ribonucleoprotein (RNP) granules, including stress granules that are formed by a
variety of RNAs and proteins under stress conditions. Stress-induced RNP granules are
considered to play important roles as part of normal stress responses in the cell and in the
pathological cascades underlying a range of human diseases including neurodegeneration.
However, the molecular basis of RNP granule formation and the full spectrum of RBP functions
remain to be elucidated. The goal of the proposed project is to investigate the molecular
mechanism of protein and RNA homeostasis related to stress-induced RNP granules and
disease-associated RBPs. The specific aims include understanding the diversity and functions
of stress-induced granules in physiological and disease-relevant conditions, elucidate the
mechanism of context-dependent granule assembly, and uncover novel functions of disease-
associated RBPs such as TIA1. We propose a series of fundamental studies that combine
biochemical, molecular, and genetic approaches and usage of state-of-art cellular and animal
models to shed light on the novel structures and pathways related to protein and RNA
homeostasis and ALS/FTD pathogenesis. Successful completion of the project is expected to
provide insights into fundamental mechanisms of neurodegeneration in ALS/FTD that may
ultimately lead to development of novel interventions to treat ALS/FTD and other relevant
neurodegenerative diseases.

## Key facts

- **NIH application ID:** 10744950
- **Project number:** 2R01NS110098-06
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Jiou Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $634,358
- **Award type:** 2
- **Project period:** 2019-02-01 → 2028-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10744950

## Citation

> US National Institutes of Health, RePORTER application 10744950, Investigating Dysregulation of Stress-related Ribonucleoprotein Granules and Functions of Associated RNA-binding Proteins in ALS/FTD (2R01NS110098-06). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10744950. Licensed CC0.

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