# ASH1L mediated transcription networks in autism spectrum disorders > **NIH NIH R01** · BROWN UNIVERSITY · 2024 · $398,332 ## Abstract PROJECT SUMMARY / ABSTRACT Chromatin modifiers and transcription factors regulating neuronal development are strongly implicated in autism spectrum disorders (ASD). ASH1L encodes a histone methyl transferase that activates developmental gene transcription. Despite being a high-confidence ASD risk gene, ASH1L- targets and functional mechanisms that underlie neurodevelopmental disorders are unknown. Our preliminary data indicates that ASH1L regulates brain development, neuronal arborization and synaptic function in human cortical excitatory neurons. Our data further suggests that during neuronal development, ASH1L antagonizes the repressor activity of Polycomb repressor complex 2 (PRC2), thereby de-repressing PRC2 target genes that are themselves high-risk ASD genes (e.g., FOXP1, RIMS1, and NRXN1α). Both ASH1L and PRC2 have been associated with the control of neuronal ar- borization and are broadly express in the developing brain. However, the extent to which the ASH1L/PRC2 axis modulate cell fate transitions and cell type specific gene programs in the human developing brain is a gap in knowledge. Our central hypothesis is that ASH1L counteracts PRC2 activity to orchestrate neuronal de- velopment by modulating cell lineage decisions and gene programs that are cell type specific. We will leverage brain organoid technology and extend the original focus of the parent grant to define how the ASH1L/PRC2 axis modulates cell fate transitions and cell type specific gene programs that will be relevant to ASD pathogenesis using human brain organoids. Specifically, we will: (1) Define how the ASH1L/PRC2 axis impacts cell fate transitions in human brain organoids and (2) Define cell type specific transcriptional programs that are modulated by the ASH1L/PRC2 axis. Completion of these aims will expand the current focus of the parent grant and will provide pre-clinical evidence and rationale for mechanism-based therapeutics. Additionally, in response to NOT-OD-24-001 we propose the following DEI activities as part of this adminis- trative supplement: (1) A high school outreach program which targets students from diverse backgrounds at the center for translational neuroscience in Brown University (see DEI statement). Our goal for this summer program is to contribute to the diversification of the pipeline of trainees to STEM careers. This program will provide exposure to scientific communication, experimental science and career development activities (see DEI statement); and (2) Direct research mentoring and career development of trainees from underserve populations (2 postbaccalaurate students, 1 undergraduate student and 1 research staff). This training will help them pursue careers in biomedical research by providing training in critical thinking, data analysis, scientific writing and sci- entific communication skills, along with opportunities to present their research at national conferences and pub- lish their work in peer review publications. ## Key facts - **NIH application ID:** 11039429 - **Project number:** 3R01MH127081-03S2 - **Recipient organization:** BROWN UNIVERSITY - **Principal Investigator:** Judy Shih-Hwa Liu - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $398,332 - **Award type:** 3 - **Project period:** 2023-01-01 → 2026-12-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/11039429 ## Citation > US National Institutes of Health, RePORTER application 11039429, ASH1L mediated transcription networks in autism spectrum disorders (3R01MH127081-03S2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11039429. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*