Neuronal Kinase Signaling in Health and Disease

Kinase signaling plays a pivotal role in regulating neuronal physiology, yet the mechanisms underlying kinase specificity, subcellular compartmentalization, and disease-associated dysfunction remain poorly understood. Dysregulated kinase activity is a key driver of neurodegenerative disorders, including Parkinson’s Disease (PD), where mutations such as LRRK2G2019S alter kinase function and neuronal survival. This project leverages innovative AI/ML algorithms, advanced CRISPR-based proteomics, and in vivo models to bridge existing gaps in our fragmentary knowledge of how kinases alter neuronal signaling and contribute to disease. By integrating a unique combination of predictive computational frameworks with experimental validation, we aim to uncover how kinases dynamically regulate proteomes in dopamine neurons and how disease-associated mutations alter allostery and rewire kinase-substrate interactions. These findings are expected to advance our understanding of kinase neurobiology, provide insights into neurological disease mechanisms, and pave the way for future therapeutic strategies targeting kinase signaling. Project Number: 1R01NS147032-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator: SCOTT SODERLING | Institution: DUKE UNIVERSITY, DURHAM, NC | Award Amount: $619,580 | Activity Code: R01 | Study Section: Neuronal Communications Study Section[NC] View on NIH RePORTER: https://reporter.nih.gov/project-details/11275895