Mathews Research Lab
Mathews Lab
Cerebellar circuits in behavior and therapies for rare neurogenetic diseases
About Our Lab
The Mathews Lab investigates how the cerebellum contributes to complex behavior and how cerebellar dysfunction leads to neurological disease. We study communication between the cerebellum and forebrain, with particular interest in the circuits that support behavioral flexibility, learning, and social behavior. By combining high-density electrophysiology, neuroanatomy, and quantitative behavioral testing, we examine how cerebellar activity influences distributed brain networks in both healthy and diseased states. Optogenetic and chemogenetic approaches allow us to directly test the roles of specific cells and circuits.
In collaboration with Neil Harris, PhD, we use functional ultrasound imaging to investigate how traumatic brain injury disrupts brain-wide functional connectivity. By tracking changes across different injury models and over time, this work seeks to identify network-level patterns associated with injury, recovery, and persistent neurological dysfunction.
A major focus of the lab is Ataxia-Telangiectasia (A-T), a rare genetic disorder that causes progressive cerebellar degeneration and severe loss of motor coordination. Using a clinically relevant ataxic mouse model developed by our laboratory, we investigate why cerebellar Purkinje neurons are especially vulnerable to the loss of ATM and how changes in cellular signaling, neuronal activity, and circuit function contribute to disease progression.
Guided by these mechanistic studies, we develop and evaluate strategies to restore ATM production and function. Our therapeutic work includes small-molecule readthrough and genome-editing approaches, including base and prime editing. We evaluate these strategies from molecular correction in patient-derived cells through in vivo delivery, neuronal function, histology, and long-term behavioral outcomes. Our goal is to unite fundamental neuroscience with therapeutic development to advance treatments for A-T and inform new approaches for other rare neurogenetic diseases.
Alert
Opportunities:
Seeking motivated undergraduates to contribute to active neuroscience and rare disease research. Opportunities are available in quantitative data analysis, mouse behavioral testing, immunofluorescence, microscopy, and image analysis.
Interested students should email Dr. Mathews with a brief cover letter describing their interests and availability, along with a current CV.
Paul Mathews, PhD
Associate Professor-in-Residence, UCLA Neurology
Investigator and Board Director, The Lundquist Institute
Executive Director, Advanced Therapeutics & Biomedical Technologies Innovation Hub