# Development of high-throughput cellular models for ASXL1-related diseases

> **NIH NIH R03** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $157,041

## Abstract

PROJECT ABSTRACT
Our broad biological goal is to develop a cell-based model that can be used to study the molecular pathogenesis
and drug responses due to mutations in ASXL1 (Additional Sex Combs Like 1). Additional Sex Like (ASXL)
genes are part of a family of genes that were originally identified as having a role in cell-fate determination in the
developing embryo. De novo, truncating mutations ASXL1 cause the pediatric syndrome, Bohring-Opitz
Syndrome (OMIM#605039). Mutations in ASXL1 are also driver mutations in acute myeloid leukemia. Despite
the clear role in multiple disease pathogenesis, the molecular function of ASXL1 remain unknown and no
targeted drugs have been approved for use in patients. This proposal builds on our work which has identified
putative epigenetic, RNA and protein biomarkers consistently altered by pathogenic mutations in ASXL1. We
will use genome-editing approaches to introduce highly sensitive and endogenous tags to our proteins-of-
interest. We will focus on introducing these tags into induced pluripotent stem cell lines as these are able to be
differentiated in multiple cell-types that are reflective of key organ systems affected in human disease. These
protein tags will allow us to study ASXL1-molecular and cellular function and to develop cell models for future
drug screens. This proposal will meet a critical need in rare disease: to develop a cell-based model system to
identify drugs that can rapidly identify pathogenic molecular changes observed in ASXL1-mutated diseased cells.

## Key facts

- **NIH application ID:** 10727983
- **Project number:** 1R03TR004645-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Valerie A Arboleda
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $157,041
- **Award type:** 1
- **Project period:** 2023-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10727983

## Citation

> US National Institutes of Health, RePORTER application 10727983, Development of high-throughput cellular models for ASXL1-related diseases (1R03TR004645-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10727983. Licensed CC0.

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