2025 Conference Highlights

The 7th Annual PACS1 Syndrome Scientific Conference

October 2025

PACS1 Foundation Funded Research Project Highlights

Institution: The Jackson Laboratory

Principal Investigator: Steve Murray, Ph.D.

Project: PACS1 Mouse Model

The PACS1 Syndrome mouse model developed at the Jackson Laboratories has been confirmed as a viable and informative model for the disease. It exhibits strong and consistent phenotypes, making it a valuable tool for testing potential therapies and understanding PACS1-related biology. The Jackson Laboratory has made the model publicly available to the research community.

Institution: The Jackson Laboratory

Principal Investigator: Steve Murray, Ph.D.

Project: Gene Editing as a Therapeutic Approach for PACS1 Syndrome

The Jackson Laboratories has identified promising base-editing vectors that can selectively inhibit expression of the mutant PACS1 allele responsible for the syndrome. These vectors are now being tested in the PACS1 mouse model for efficacy and will help determine whether base-editing is a feasible approach for treating PACS1 Syndrome in the future.

Institution: UT Southwestern Medical Center

Principal Investigator: Evan Nair-Gill, M.D., Ph.D.

Project: Exploring the Structural Biology of the PACS1 – WDR37 Connection

Dr. Evan Nair-Gill and his team at UT Southwestern Medical Center are continuing to advance structural biology research on PACS1 Syndrome. They recently published a paper (available on bioRxiv) which shows that the proteins Pacs1 and Wdr37 tightly bind together to stay stable and function properly. The disease-causing PACS1-R203W mutation does not break this bond but still relies on Wdr37 for stability. Finding a small molecule that can break the PACS1-Wdr37 bond might also lower levels of the toxic mutant Pacs1 Protein, offering a new potential treatment strategy for PACS1 syndrome.

Funded Partners: Olink and the Gleeson Lab

Project: Proteomics Analysis to Uncover Biomarkers in PACS1 Syndrome

Olink and the Gleeson Lab are collaborating to analyze PACS1 patients and control plasma samples using advanced proteomics technology. The goal is to identify potential biomarkers for PACS1 Syndrome, which could help measure the effectiveness of future treatments for PACS1 Syndrome.

Institution: Northwestern University

Principal Investigator: Dr. Alicia D. Guemez-Gamboa

Project: Characterization of Neuronal Properties of PACS1 Syndrome Mouse Model

Dr. Alicia D. Guemez-Gamboa and her team at Northwestern University are importing colonies of PACS1 Syndrome mouse models from The Jackson Laboratory. Once established, they will conduct electrophysiological studies on the mice to better understand how the PACS1 mutation affects neuronal activity and brain function. These insights will help researchers better understand the biology of the disease and guide the development of targeted treatments for PACS1 Syndrome.