# Effects of Extracellular Mechanics on Mechanosensory and Central Neuron Function

> **NIH NIH K00** · DANA-FARBER CANCER INST · 2024 · $94,230

## Abstract

DESCRIPTION (provided by applicant): Cerebrovascular dysfunction accompanies nearly all of the
known forms of tauopathies--a form of neurodegenerative disorders that result in impaired memory,
executive function, and general cognitive decline. Recent efforts to understand the mechanisms
underlying traumatic brain injury (TBI) have revealed several startling similarities between the
pathologies associated with neurodegenerative diseases and those following TBI. Combined, these
findings suggest a potential relationship between aberrant neural mechanical and stress cognitive
decline. Neurovasculature and the network of ventricles and aqueducts within the brain are known to
fluctuate in volume with changes in blood flow and age--both of which are risk factors for dementia.
Central neurons surrounding these dynamic structures are hypothesized to possess multiple types of
molecular protein sensors that respond to physical environmental changes, though few studies have
directly studied these receptors and their role in health and disease. To address this knowledge gap,
the work proposed here aims to quantify the effects of the extracellular mechanical environment on
neural function. To achieve this aim, the candidate will achieve two proposed scientific aims first as a
PhD student during the F-99 phase of the award, and then as a postdoctoral scholar during the K-00
phase of the award. The first aim of this proposal presents dissertation research completed to date by
the candidate in the sponsor’s lab. This completed research demonstrates the feasibility of the work
proposed in Aims 2 and 3. In Aim 2, the candidate will continue their research studying the effects of
extracellular mechanics on mechanosensory neuron function in an invertebrate model, C. elegans,
whose touch sensation mirrors touch receptors in the human peripheral nervous system. This work
combines state-of-the-art, correlative force spectroscopy and fluorescence microscopy with neuronal
culture in three-dimensional, tunable, viscoelastic substrates. For the K-00 phase of this award, as
described in Aim 3, the candidate will extend the clinical relevance of this work by studying i n vitro
neural mechanics in vertebrate models of disease. Broadly, the candidate’s research interest for the
postdoctoral scholarship is to (1) identify intracranial sources of mechanical strain, (2) address how
these strains alter central neuron function, and (3) use these findings as a springboard for identifying
novel classes of mechanoreceptors in central neurons. The training support provided by this award will
serve as a springboard with which the candidate will launch their career as an independent
neuroscientist, working at the interface of engineering and neuroscience to identify
mechanotransduction signalling pathways in central neurons and their role in neurodegeneration. The
candidate’s long-term career goal is to establish a research program that will employ an understanding
of basic neurobiology t...

## Key facts

- **NIH application ID:** 10760267
- **Project number:** 5K00AG078230-05
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Joy Ann Franco
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $94,230
- **Award type:** 5
- **Project period:** 2019-09-23 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10760267

## Citation

> US National Institutes of Health, RePORTER application 10760267, Effects of Extracellular Mechanics on Mechanosensory and Central Neuron Function (5K00AG078230-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10760267. Licensed CC0.

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