An iPSC-based Platform for Characterization of Neuronal Circuit Dysfunction in RASopathies

MDBRRASopthies
Written By Million Dollar Bike Ride

Awardee: Sattar Khoshkhoo

Institution: Brigham and Women's Hospital

Grant Amount: $58,222

Funding Period: February 1, 2025 - January 31, 2026

Summary:

RASopathies are a group of genetic disorders that affect multiple body systems and are often linked to neurocognitive issues like learning disabilities, autism, and epilepsy. These conditions arise due to overactive Ras-MAPK signaling, which plays a crucial role in brain development and function. However, the specific effects of Ras-MAPK overactivation on brain circuits are not well understood. This project aims to use patient-derived stem cells to model RASopathies and investigate how abnormal signaling impacts brain cell communication. Moreover, by testing drugs that inhibit the Ras-MAPK pathway, this proposal will evaluate the feasibility of using Ras-MAPK inhibitors as a therapeutic strategy to restore normal brain activity in affected individuals. This research platform will also enable future drug discovery for rare genetic diseases that affect brain circuits.

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