MET receptor tyrosine kinase: From neurodevelopment to neurodegeneration

College of Medicine – Tucson Department of Pharmacology

When

11 a.m. – Noon, Sept. 11, 2024

Where

Arizona Health Sciences Center, Room 8403
1501 N. Campbell Ave., Tucson, AZ 85724

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Abstract:  The long-term mission of the Qiu laboratory is to understand how genetic risk factors predispose an individual for neurodevelopmental disorders, including autism, by affecting the normal brain development trajectory and its physiological function. They strive to apply a ‘precision medicine in psychiatry’ approach to dissect how risk genes affect specific neuronal types and circuits across the protracted neurodevelopmental timeline. Qiu is also interested in neurocircuit basis of behavior, and molecular and synaptic basis of aging and neurodegeneration. One NIH-funded research project is to investigate the role of MET receptor tyrosine kinase, an established prominent autism risk factor, on forebrain development. Findings suggest that MET signaling serves as a critical intrinsic neural mechanism that regulates dendritic spine formation and synaptogenesis. Current lab efforts focuses on important roles of MET in synapse pruning, maturation, refinement of circuit connectivity and the emergence of social behavior, by utilizing several novel MET mutant mice lines created in the lab. In addition to its neurodevelopmental role of MET, MET signaling may play a key role in aging/degenerating brain. Recent findings indicate that MET protein, heavily expressed in the excitatory neurons during early brain development, is reduced in Alzheimer's disease brain. The sole ligand for MET, hepatocyte growth factor or HGF, found to be primarily expressed in astrocytes, is elevated in the cerebrospinal fluid in Alzheimer's disease patients, and is associated with small vessel pathology in Alzheimer's disease and dementia. Activation of MET by HGF initiates a pleiotropic signaling that is neurotrophic and neuroprotective in multiple neurodegenerative mouse models ranging from multiple sclerosis, Parkinson’s disease, to ALS. Built on these key literature and preliminary findings, they are currently testing the hypothesis that re-activating MET signaling promotes functional synaptogenesis and protects against synapse loss and degradation of circuit connectivity associated with aging, neurodegeneration and other neurological conditions

Presenter Details

Shenfeng Qiu, MD, PhD
Professor, Basic Medical Sciences
University of Arizona College of Medicine – Phoenix
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