Overview

Mayo Clinic's Molecular Neurotherapeutics Laboratory, led by Tsuneya Ikezu, M.D., Ph.D., focuses on the identification and therapeutic intervention of target molecules and cell types for the treatment or prevention of neurodegenerative disorders, such as Alzheimer's disease and other tauopathies.

Neurodegenerative disorders

The primary focus of our lab is to understand how tau protein propagates in a stereotypical manner in the brain of a patient with Alzheimer's disease (AD). Our research recently identified that microglia and exosomes — nanoscale extracellular vesicles secreted from cells — mediate the spread of pathogenic tau protein in animal models of AD. We are interested in understanding the molecular composition, the cellular origin, transporting machinery, and cellular destination of exosomes in animal and human brains.

Neurodevelopmental disorders

Dr. Ikezu's lab is interested in the role of microglia in the pathobiology of autism spectrum disorder (ASD). Environmental factors, such as infection, environmental pollutants and maternal stresses, are emerging risks of ASD. Systemic infection in the first trimester of pregnancy is known to increase the risk of ASD in the offspring. We hypothesize that such environmental factors dysregulate brain development through microglial dysfunction. We employ system biological approaches to comprehensively characterize the microglial and neuronal development in animal models of ASD.

Human iPSC research

Human induced pluripotent stem cells (iPSCs) are powerful tools to reconstitute the interaction of human neuronal and immune cells in tissue culture models. We are remodeling the central nervous system (spheroids) consisting of many neuronal cell types using human iPSCs derived from healthy and disease cases. These models are being tested using confocal microscopy, electrophysiology, RNA sequencing and proteomics.

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