# Investigating Pathogenic Mechanisms of Frontotemporal Dementia Caused by Mutations in CHMP2B and TBK1

> **NIH NIH R37** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2022 · $654,088

## Abstract

ABSTRACT
Frontotemporal dementia (FTD) is a progressive neurodegenerative disease associated with focal atrophy of
the prefrontal and/or temporal lobes. FTD is the second most common form of dementia among people under
the age of 65. Many FTD-causing genes have been identified during the last decade, including CHMP2B,
GRN, C9ORF72, and TBK1. Some of these genes are also implicated in the motor neuron disease
amyotrophic lateral sclerosis (ALS), paving the way for in-depth mechanistic investigation of pathogenic
processes in both disorders. In order to reveal common pathogenic mechanisms in different forms of FTD, it is
critically important to investigate both common and rare genetic mutations. To this end, in this application, we
will focus on the effects of FTD-causing mutations in CHMP2B and TBK1 on the functions of the endosomal-
lysosomal and autophagy pathways, two closely linked cellular pathways for degradation of transmembrane
and intracellular cargos. We will take advantage of strengths of different experimental systems including fruitfly
Drosophila, mouse models of FTD and cortical neurons differentiated from CRISPR-engineered induced
pluripotent stem cells (iPSCs). This multidisciplinary approach will greatly enhance our understanding of
pathogenic mechanisms of FTD and reveal novel targets for therapeutic intervention.

## Key facts

- **NIH application ID:** 10536397
- **Project number:** 4R37NS057553-16
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Fen-Biao Gao
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $654,088
- **Award type:** 4N
- **Project period:** 2018-01-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10536397

## Citation

> US National Institutes of Health, RePORTER application 10536397, Investigating Pathogenic Mechanisms of Frontotemporal Dementia Caused by Mutations in CHMP2B and TBK1 (4R37NS057553-16). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10536397. Licensed CC0.

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