# Molecular mechanisms underlying vocal communication

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $390,056

## Abstract

Project Summary
The molecular pathways underlying cognition and vocal communication remain largely unknown. The genes and
mechanisms governing these processes are disrupted in many neurodevelopmental disorders, including
intellectual disability and autism spectrum disorder. The long-term goal of our laboratory is to study the normal
function of genes disrupted in disorders with deficits in cognition, communication, and social behavior, to gain
mechanistic understanding that can be leveraged for treatment opportunities. Mutations in the gene encoding
the ubiquitin ligase UBE3B have been identified in patients with intellectual disability and lack of speech. The
specific mechanism(s) that give rise to the neurodevelopmental phenotypes and the UBE3B substrates that
mediate these mechanisms are completely unknown. Our preliminary studies suggest a role for UBE3B in brain
development and vocalization. In addition, we identified the branched-chain a-ketoacid dehydrogenase kinase
(BCKDK) as a substrate for UBE3B. We propose to dissect the molecular networks regulated by UBE3B
and its role in mediating vocalization, through the following three specific aims: 1) Determine the role of
UBE3B in vocalization; 2) Identify the neuronal substrates of UBE3B through quantitative proteomics and
biochemical validation experiments; 3) Rescue the neurodevelopmental phenotypes associated with UBE3B loss
of function by targeting its substrate BCKDK. Together, these aims will identify the molecular networks regulated
by UBE3B that may underlie the lack of speech and other neurodevelopmental phenotypes observed in patients
with UBE3B disruption. Successful completion of the proposed aims will provide new insights into pathways
regulating vocalization, increase our knowledge of the specific pathogenic mechanism underlying
neurodevelopmental disorders with communication deficits, and examine new therapeutic approaches.

## Key facts

- **NIH application ID:** 10737609
- **Project number:** 5R01HD099162-05
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Maria Chahrour
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $390,056
- **Award type:** 5
- **Project period:** 2019-12-15 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10737609

## Citation

> US National Institutes of Health, RePORTER application 10737609, Molecular mechanisms underlying vocal communication (5R01HD099162-05). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/10737609. Licensed CC0.

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