Investigator:
Aryeh Zolin, MD, PhD
Name of Institution:
Weill Medical College of Cornell University
Project Title:
Trans-Synaptic Propagation of Alpha-Synuclein Aggregates In Vivo from Genetically Select Neural Populations
Investigator Bio:
Dr. Aryeh Zolin is a Movement Disorders Fellow at Weill Cornell Medicine/NewYork-Presbyterian Hospital and a researcher at the Feil Family Brain and Mind Research Institute. He received his undergraduate degree from Columbia University in 2010. He then attended medical school at Weill Cornell Medicine (2021) and earned his PhD at the Rockefeller University (2019) as part of the Tri-Institutional MD/PhD Program. His graduate work was performed in Dr. Vanessa Ruta’s laboratory of neurophysiology and behavior. Dr. Zolin completed his clinical training in neurology at Weill Cornell Medicine/NewYork-Presbyterian Hospital in 2025, where he was the McGraw Fellow in Neurology Research.
Dr. Zolin’s research is focused on how Parkinson’s disease (PD) and related neurodegenerative disorders begin and progress over time. He is working in the laboratories of Drs. Jacqueline Burré and Manu Sharma to develop a mouse model that examines how the pathology that underlies PD spreads through the brain. Results from this research will provide insight into the pathogenesis of PD and identify potential drug targets to slow or stop disease progression.
Objectives/Background:
To determine how the pathology that causes neurodegeneration in PD is transmitted between neurons in the brain.
PD is caused by the misfolding and clumping of the protein alpha-synuclein (aSyn). These misfolded proteins can spread from one brain cell to another, causing healthy aSyn to misfold and form toxic clumps. Interestingly, not all brain regions are equally affected – some are more vulnerable to aSyn spread than others. Scientists still don’t know exactly how misfolded aSyn leaves one cell and enters another, which makes it hard to design treatments that stop the spread. This project will develop a mouse model to uncover how aSyn travels between neurons and why certain regions of the brain are hit first in PD.
Methods/Design:
This project will use a combination of genetic, biochemical, and surgical techniques to trigger aSyn misfolding and clumping in specific groups of brain cells in mice. The mice will be tested for movement changes over time, and their brains will be examined using advanced 3D imaging to track exactly where and how aSyn spreads. By comparing results in different types of neurons, we can learn how cell properties, brain wiring, and molecular makeup influence aSyn transmission and disease progression.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
This project will help explain how toxic aSyn clumps move through the brain and why some cells are more prone to damage. By revealing the molecular entry and exit routes for these misfolded proteins in mice, the work will point to new ways to block their spread. This could lead to the development of drugs or therapies that slow or even stop PD progression, protecting brain cells and preserving movement and quality of life for people with the disease.