The Translational Genomics Research Institute (TGen), part of City of Hope, today announced it has been selected as part of a national team to join the Collaborative Research Network (CRN), an international, multi-institutional initiative focused on addressing high-priority research questions in Parkinson's disease. Members also include researchers from the Beckman Research Institute of City of Hope, Denali Therapeutics, Johns Hopkins University School of Medicine, the National Institute on Aging at the National Institutes of Health, The Ohio State University, and the University of Alabama at Birmingham. The CRN is a worldwide network of 67 research teams, nearly 400 investigators, and 187 institutions across 22 countries working together on high‑priority questions in Parkinson's disease.

Supported by a grant from Aligning Science Across Parkinson's (ASAP), in partnership with The Michael J. Fox Foundation for Parkinson's Research (MJFF), the team will examine how these biological factors influence disease development. Parkinson's disease affects nearly one million people in the United States. Although treatments can help manage symptoms, there is still no cure, and scientists are working to understand why the disease develops and why it affects people so differently.

This collaboration brings together expertise in lysosome biology, secreted molecules, neurodegeneration, and molecular analysis to better understand the biological processes driving Parkinson's disease. By combining complementary expertise across institutions and disciplines, the team aims to uncover mechanisms that could guide future therapeutic strategies.

Many of the changes that occur in Parkinson's disease begin long before symptoms appear, but we still know remarkably little about how stressed cells communicate dysfunction and how these signals contribute to disease. By combining complementary expertise and advanced imaging technologies, our team aims to uncover molecular signals that could ultimately enable more precise approaches to diagnosing and treating Parkinson's disease."

Kendall Van Keuren-Jensen, Ph.D., TGen vice president for research, professor in the Bioinnovation and Genome Sciences Division, and principal investigator on the study

The study, Investigating the impact of Parkinson's disease lysosomal risk variants on lysosomal function and alpha‑synuclein clearance across CNS cell types, will investigate how genes linked to Parkinson's affect lysosome function, why some brain cells are more vulnerable than others, and which molecules are released by stressed cells and whether they can be used as early warning signs of disease. TGen scientists will apply their expertise in studying extracellular RNA, tiny molecules released by cells. These molecules may serve as biomarkers, measurable signals in blood or other fluids, which could help detect Parkinson's earlier or guide more patient-specific treatments.

"Lysosomes are small, membrane-bound organelles that play a critical role in cellular clearance and waste management," said Luis Bonet-Ponce, Ph.D., of The Ohio State University. "When the lysosomal membrane is damaged or stressed, its contents can leak into the cytosol, triggering cellular stress responses and, if unresolved, cell death. Emerging functional genetic evidence suggests that lysosomal membrane damage is an important mechanism underlying PD. Understanding how genetic and environmental risk factors affect lysosomal membrane integrity could significantly advance our understanding of PD pathobiology and identify new opportunities for therapeutic intervention."

Anastasia Henry, Ph.D., of Denali Therapeutics adds that "understanding how Parkinson's disease-associated genetic variants disrupt lysosomal function is essential to help translate basic discoveries into new therapeutic approaches. This collaboration brings together complementary expertise and technologies across both industry and academia to advance these efforts with the ultimate goal of informing the development of more targeted therapies for people living with Parkinson's disease."

The project's secretome studies will also include contributions from Tijana Jovanovic‑Talisman, Ph.D., an associate professor in the Department of Cancer Biology and Molecular Medicine at the Beckman Research Institute of City of Hope, and Steve Gould, Ph.D., a professor in the Department of Cell Biology at Johns Hopkins School of Medicine.

"Using super-resolution imaging, our team will help track the molecular signals released by stressed cells to better understand how disease begins at the cellular level," said Jovanovic-Talisman, an expert in single-molecule imaging, nanobiology, and extracellular vesicle analysis. "By decoding this communication, our team hopes to identify biomarkers that could enable earlier diagnosis of Parkinson's disease and support the development of more effective, personalized treatments."

ASAP is expanding the CRN to map the biological blueprint of Parkinson's disease and create a shared, standardized set of research tools that help turn discoveries into treatments. The next phase centers on understanding how Parkinson's differs from person to person, what drives that variation, and how those insights can lead to more precise diagnostics and future therapies. This work also includes developing resources that provide researchers around the world a common starting point, lowering technical barriers that often slow drug development.

"We have known for some time that high levels of alpha-synuclein expression can be a trigger for neurodegeneration, especially in neurons that are vulnerable in Parkinson's disease. What this project aims to address is how cells other than those that are very vulnerable indirectly influence cell survival," said Mark R. Cookson, Ph.D., Senior Investigator, Laboratory of Neurogenetics, National Institute on Aging at the National Institutes of Health.

ASAP launched the CRN in 2020 to accelerate Parkinson's disease research through open, team‑based science. Its mission is to accelerate the pace of discovery and inform the path to a cure for Parkinson's disease (PD) through collaboration, research-enabling resources, and data sharing.