# Developing Tools to Probe DnaJB6 Dynamics in Spinobulbular Muscular Atrophy

> **NIH NIH K99** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $118,800

## Abstract

PROJECT SUMMARY/ABSTRACT
 Spinobulbar Muscular Atrophy (SBMA) is an incurable neurodegenerative disorder that is characterized
by the toxic accumulation of mutated androgen receptor (polyQ-AR) proteins. The molecular chaperone protein
DnaJB6 is specialized to prevent polyQ-AR aggregation in cells and suppress disease phenotypes by preventing
polyQ-AR aggregation and recruiting another chaperone protein, Hsp70 to polyQ-AR. While DnaJB6 represents
an exciting target for developing SBMA chemotherapeutics, its dynamic protein-protein interactions and complex
structure present significant challenges for efforts to discover and design DnaJB6 chemical ligands.
 DnaJB6 associates with itself to form complexes that appear to exchange between larger and smaller
oligomeric states over time. I hypothesize that binding to either polyQ-AR or Hsp70 causes changes in the
stability of DnaJB6 complexes, and that these changes in DnaJB6 dynamics can be exploited to discover
chemical probes. DnaJB6 chemical probes could then be used to probe pathological aggregation in SBMA. To
test this hypothesis, I will characterize DnaJB6 complex stability and discover chemical matter that tunes DnaJB6
activity in the K99 phase of this award. In the R00 phase, I will use these molecules to probe SBMA in cell and
animal models. This work is significant because the tools resulting from my studies will not only have applicability
for studying SBMA, but also for other neurodegenerative disease where DnaJB6 can suppress protein
aggregation (i.e. Huntington's Disease, Spinocerebellar Ataxias, and Parkinson's Disease) and chaperone
biology more broadly. My proposed studies are innovative, as they will yield the first DnaJB6-targeted chemical
probes and a novel strategy to understand the molecular underpinnings of SBMA.

## Key facts

- **NIH application ID:** 10515844
- **Project number:** 1K99NS128717-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Oleta Tanitrea Johnson
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $118,800
- **Award type:** 1
- **Project period:** 2022-08-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10515844

## Citation

> US National Institutes of Health, RePORTER application 10515844, Developing Tools to Probe DnaJB6 Dynamics in Spinobulbular Muscular Atrophy (1K99NS128717-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10515844. Licensed CC0.

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