Thursday, August 7, 2025 8/7/2025

Unraveling the Genetic Programs Engaged in ASD Neurons Through Coupled Transcriptomic and Phenotypic Readouts

Award Number: R01MH128366
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/10/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2027

Group Awards By:

View Award Description

Unraveling the Genetic Programs Engaged in ASD Neurons Through Coupled Transcriptomic and Phenotypic Readouts - Autism spectrum disorders (ASD) are genetically diverse, characterized by both rare variants of large effect size and common variants of small effect size. Identifying the molecular mechanisms resulting from these variants presents a key challenge for the development of clinical interventions. Human pluripotent stem-cell derived neurons (hPSC-Ns) allow studies against a human genetic background, and show altered morphology and electrophysiology in ASD conditions. However, identifying mechanisms remains difficult with small numbers of lines, especially for common genetic variants. To overcome this challenge, we will leverage multi-omic characterization of hPSC-Ns perturbed with CRISPRi knockdown of both large effect size ASD risk genes and genes related to neuronal morphology (Aim 1) and electrophysiology (Aim 2). We will complement these screens with a characterization (Aim 3) of a larger, diverse cohort of 46 ASD lines and 46 matched controls which do not harbor coding variants in the genes perturbed in the previous Aims. An integrative analysis of this data (Aim 4) will generate interpretable genetic signatures related to each of these phenotypes and will show how these signatures interact with ASD risk genes. This approach is made possible by new techniques for pooled stem cell culture developed in Dr. Ralda Nehme’s lab, high content optical profiling methods developed by Dr. Samouil Farhi’s team, and data integration tools developed by Dr. Ernest Fraenkel’s group. The overall project will provide a basic neurobiological understanding of hPSC-Ns; provide valuable insight into how both common and rare variants induce observed cell-intrinsic phenotypes; and define an analytic framework and genetic signatures which can be used to understand mechanistic recruitment of new genetic risk loci and other psychiatric diseases.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $738,884 )
2025	2025	THE BROAD INSTITUTE, INC	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Mental Health Research Grants	000	4	7/8/2025	NON-COMPETING CONTINUATION	$738,884
														Subtotal = $738,884

Issue Date FY: 2024 ( Subtotal = $754,423 )
2024	2024	THE BROAD INSTITUTE, INC	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Mental Health Research Grants	000	3	7/2/2024	NON-COMPETING CONTINUATION	$754,423
														Subtotal = $754,423

Issue Date FY: 2023 ( Subtotal = $731,446 )
2023	2023	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Mental Health Research Grants	000	2	6/28/2023	NON-COMPETING CONTINUATION	$731,446
														Subtotal = $731,446

Issue Date FY: 2022 ( Subtotal = $761,381 )
2022	2022	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Mental Health Research Grants	000	1	8/9/2022	NEW	$761,381
														Subtotal = $761,381

Grand Total All Awards = $2,986,134

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Unraveling the Genetic Programs Engaged in ASD Neurons Through Coupled Transcriptomic and Phenotypic Readouts

Award Number: R01MH128366

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/10/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer