# Toward 3D human brain-like tissues for targeting dysregulated synapse and proteostasis mechanisms in autism spectrum disorder

> **NIH NIH F32** · TUFTS UNIVERSITY MEDFORD · 2020 · $70,310

## Abstract

TOWARD 3D HUMAN BRAIN-LIKE TISSUES FOR TARGETING DYSREGULATED SYNAPSE AND
 PROTEOSTASIS MECHANISMS IN AUTISM SPECTRUM DISORDER
Autism spectrum disorder (ASD) is a neurodevelopmental disease affecting nearly 1/50 children in US with an
estimated $268 billion in annual costs. The disease is characterized by significant behavioral abnormalities that
are often devastating to the quality of life for these patients. Behavior is directly related to the underlying changes
of the central nervous system (CNS) brain tissue. Alterations in synapse maintenance and proteostasis pathways
are found across ASD model systems, implicating a potential unifying approach for treating ASD. However, our
knowledge of these two processes in both healthy and diseased, human relevant conditions is still limited. To
deepen our understanding of the interconnectedness between these two fundamental processes in humans, the
present application seeks to bioengineer 3D, human brain-like tissues. In addition to providing insight into the
biology underlying disease, these tissues can be utilized to develop novel approaches to target identified
aberrant mechanisms. As an initial starting point into building 3D ASD brain-like models, we propose to begin
with cells from donors with a well-studied monogenetic, ASD-related disorder, Fragile-X syndrome (FXS). This
approach will allow us to validate our model with a disorder which results in well documented phenotypic features.
Our models will incorporate induced pluripotent stem cell (iPSC) derived neurons, astrocytes, and microglia
(iNeurons, iAstrocytes, iMicroglia) to recapitulate 3D cell-cell interactions important for synapse maintenance.
As such, we propose the following two Specific Aims:
Aim 1: Develop a long-term 3D culture system compatible with relevant CNS cell types and outcomes (tissue
level functionality, synapse/dendritic spine analyses, and proteostasis pathway biochemical analyses).
Aim 2: Compare FXS-iPSC-based neuronal cultures vs. “healthy”, genetically corrected iPSC neuronal cultures
with respect to synapse maintenance and proteostasis.

## Key facts

- **NIH application ID:** 9998745
- **Project number:** 5F32MH118678-03
- **Recipient organization:** TUFTS UNIVERSITY MEDFORD
- **Principal Investigator:** Joshua Dean Erndt-Marino
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $70,310
- **Award type:** 5
- **Project period:** 2018-09-17 → 2021-09-16

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9998745

## Citation

> US National Institutes of Health, RePORTER application 9998745, Toward 3D human brain-like tissues for targeting dysregulated synapse and proteostasis mechanisms in autism spectrum disorder (5F32MH118678-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9998745. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*