# Gaining insight into psychiatric disease by engineering piece by piece the human brain in vitro.

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $650,516

## Abstract

ABSTRACT
A critical challenge in understanding the intricate programs underlying development, assembly,
function, and dysfunction of the human nervous system is the lack of direct access to intact,
functioning human brain tissue for detailed investigation by imaging, recording, and stimulation.
My laboratory has been developing methods for directed differentiation of region-specific brain
organoids and we have shown that these can combined two by two to study cell-cell interactions
and circuit formation in preparations called brain assembloids. However, current in vitro brain
models derived from stem cells do not capture neuromodulatory input, which restrict broader
applications in neuroscience and modeling of disease. Here, we propose to develop a human 3D
cellular platform that includes neuromodulatory projections. More specifically, we will derive
from pluripotent stem cells regionalized brain organoids resembling the nucleus raphe in the
brainstem and containing serotonergic neurons, and subsequently assemble them with cortical
organoids. Using state-of-the-art live imaging, transcriptomics, pharmacology, viral tracing and
electrophysiological methods, we plan to study serotonergic input into the cerebral cortex and use
this platform to investigate defects in neuronal cross-talk in a severe genetic form of
neurodevelopmental disease.

## Key facts

- **NIH application ID:** 10052640
- **Project number:** 2R01MH107800-06
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Sergiu Pasca
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $650,516
- **Award type:** 2
- **Project period:** 2015-08-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10052640

## Citation

> US National Institutes of Health, RePORTER application 10052640, Gaining insight into psychiatric disease by engineering piece by piece the human brain in vitro. (2R01MH107800-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10052640. Licensed CC0.

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