December 12, 2025
FRAXA Research Foundation
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Uncovering the Dynamics of FMR1 Using Spatial Transcriptomics

Drs. Oswald Steward and Patricia Pirbhoy in their laboratory, studying RNA localization and gene activity in Fragile X syndrome using spatial transcriptomics.
Dr. Oswald Steward and Dr. Patricia Pirbhoy study how loss of the Fmr1 gene affects RNA localization and gene activity in Fragile X syndrome.
Oswald Steward, PhD
Principal Investigator
Patricia Salgado Pirbhoy, PhD
FRAXA Fellow
University of California, Irvine
Irvine, CA
2025-2026 Grant Funding: $100,000

Summary

This team is studying how the Fragile X protein, FMRP, influences where and when genes are active in the brain. Drs. Oswald Steward and Patricia Pirbhoy will examine how and where messenger RNAs (mRNAs) move and function in different brain regions during learning. Their findings could reveal how disrupted RNA localization contributes to Fragile X symptoms and point toward treatment strategies which specifically target key signaling pathways.

The Science

This project aims to uncover how the loss of FMRP disrupts the way neurons manage messenger RNAs (mRNAs), which carry instructions for making proteins essential to brain function.

In a healthy brain, FMRP helps guide these mRNAs to the right place in the neuron at the right time. This coordination is especially important when the brain is active and forming memories. Without FMRP, this process may break down, leading to problems with synaptic plasticity, learning, anxiety, and behavior.

To study this, Dr. Steward’s team will:

  • Use spatial transcriptomics from 10X Genomics to map how and where mRNAs are located and activated in different brain regions during learning.
  • Investigate sex differences in two key systems — the endocannabinoid (eCB) system and cholecystokinin (CCK) signaling — both linked to anxiety and cognitive function.
  • Measure cognitive flexibility, or the ability to adapt to new rules, in Fragile X model mice and determine how it varies between males and females.
  • Develop new bioluminescent tools to track how RNA molecules behave in real time inside living brain cells.

Together, these studies will help explain how loss of FMRP disrupts not only the production of proteins but also the timing and location of gene expression. By combining molecular and behavioral analyses, this project could reveal new therapeutic directions that account for sex-specific differences and understudied signaling systems in Fragile X syndrome.

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