# The Role of DNAJB6 in Muscle and the Impact of LGMD1D Mutations

> **NIH NIH K08** · WASHINGTON UNIVERSITY · 2022 · $139,134

## Abstract

The goal of this mentored career development award is to facilitate the PI’s transition to independence as a
physician-scientist with clinical expertise in neuromuscular medicine and a research emphasis in the molecular
mechanisms of myopathies. The candidate is an MD neuromuscular neurologist with a background in genetics,
myology, and molecular mechanisms and therapeutic strategies for hereditary myopathies. The award will
help the candidate achieve his short-term goal, to gain experience in advanced muscle degeneration research
methods, including in-vivo imaging, integrative physiology techniques as well as stem cell skeletal muscle
culture. The award will also help facilitate his transition to an independent investigator with an independent
laboratory. It will also help position the candidate to achieve his long-term goal of becoming a successful and
productive physician scientist and establishing a muscular dystrophy center focused on accelerating the pace
of scientific discovery and its application to the care of individuals with myodegenerative diseases.
The environment in which the proposed research will be conducted is outstanding. The candidate’s primary
mentors, Drs. Chris Weihl and Alan Pestronk, are internationally respected scientists and neuromuscular
neurologists with proven track records of excellence in training junior faculty. The merger of these two diverse
scientists fosters an environment that will allow the candidate to become an independent investigator. The
proposed research will delineate the pathomechanism of DNAJB6 disease mutations and develop treatment
strategies for limb girdle muscular dystrophy type 1D (LGMD1D) patients. Muscular dystrophies are a
heterogeneous group of untreatable muscle diseases. Protein chaperones, or heat shock proteins (HSPs) are
critical for skeletal muscle health. Recently mutations in DNAJB6, an HSP40 co-chaperone, were found to
cause limb girdle muscular dystrophy 1D (LGMD1D), an adult onset progressive myopathy with vacuolar and
aggregate myopathology. DNAJB6’s role in normal muscle, and how mutations cause myopathy, is unknown.
The central hypotheses to be tested are: LGMD1D mutations in DNAJB6 alter its baseline localization and
kinetics within skeletal muscle (1), suppress downstream myogenic signaling pathways (2), and impair their
response to myofibrillar stress (3).
Clarifying DNAJB6’s role as a central hub linking sarcomeric protein homeostasis with gene expression will
provide insights into LGMD1D pathogenesis and therapeutic strategies as well as for other primary
chaperonopathies and common disorders of skeletal muscle chaperone dysfunction. This career development
award is an ideal mechanism to provide the candidate with valuable research training to complement his
clinical focus in neuromuscular disorders and help develop a skill set for translating basic science discoveries
into effective therapies for patients with myopathies.

## Key facts

- **NIH application ID:** 10450670
- **Project number:** 5K08AR075894-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Andrew Findlay
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $139,134
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10450670

## Citation

> US National Institutes of Health, RePORTER application 10450670, The Role of DNAJB6 in Muscle and the Impact of LGMD1D Mutations (5K08AR075894-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10450670. Licensed CC0.

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