# UCLA High-Throughput Neuropsychiatric Disorder Phenotyping Center (UCLA HT-NPC)

> **NIH NIH RM1** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $1,882,490

## Abstract

Project Summary/Abstract
Human genetic studies have identified hundreds of genes contributing to Neuropsychiatric and Neurodevelop-
mental Disease (NPD) risk. But for most genes, their normal function or the consequences of their absence or
reduction on neurodevelopment and neural function are not known. Here, we propose to address the substantial
challenges of discerning potential functions of hundreds of NPD genes through the development of a High
Throughput Neuropsychiatric Disease Phenotyping Center (UCLA HT-NPC), driven by the activity of 9 highly
collaborative investigators (Aharoni, Bhaduri, Damoiseaux, Geschwind, Golshani, Kitai, Luo, Novich, and Wells)
and two substantial core facilities (UCLA Molecular Screening Shared Resource and the Human Stem Cell and
Genome Engineering Center). Through a tiered approach, we combine high throughput and high value,
quantitative phenotyping with stem cell engineering to characterize the functional consequences of NPD gene
knockouts (null alleles), a key initial step that will inform our understanding of disease pathways. In the first step,
we will rapidly generate null alleles for 250 genes chosen by the Consortium using a rapid, high throughput
lentiviral based system in hESCs. Viability and neural induction potential will be assessed, and quantitative
phenotyping conducted using RNA-seq on all lines. Those genes passing viability and neural induction tests will
be used in the production of clonal null hiPSC lines (male and female) for downstream phenotyping and wider
distribution to the community. Subsequently, we will perform high throughput, quantitative, multi-scale
phenotyping at the molecular, morphological, and physiological levels in both 2D and 3D hiPSC-based models
of human cortical development. We leverage the relative strengths and scalability of each model to enable us to
perform both snRNA and bulk RNA-seq, measure the maturation, morphology, and synaptic density of neural
cells using automated imaging, including the multiplexed, protein-based CODEX (Phenocycler) platform, and
characterize neuronal activity and synchronization through optical recordings using custom-built mini-scope
arrays (STIMscope). By using multiple systems (e.g. hESC/hiPSC; gene editing, 2D and 3D cultures), we test
biological reproducibility across systems and technical reproducibility through replication. The use of
experimentally validated, quantitative phenotypes across multiple scales of analysis facilitates data sharing and
comparisons with other SSPsyGene investigators and provides a template for the field more broadly.

## Key facts

- **NIH application ID:** 10833176
- **Project number:** 5RM1MH132651-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** DANIEL H GESCHWIND
- **Activity code:** RM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,882,490
- **Award type:** 5
- **Project period:** 2023-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10833176

## Citation

> US National Institutes of Health, RePORTER application 10833176, UCLA High-Throughput Neuropsychiatric Disorder Phenotyping Center (UCLA HT-NPC) (5RM1MH132651-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10833176. Licensed CC0.

---

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