Tsuneya Ikezu, M.D., Ph.D.

2023-08-15 01:26| 来源: 网络整理| 查看: 265

SUMMARY

Research in Mayo Clinic's Molecular Neurotherapeutics Laboratory, led by Tsuneya Ikezu, M.D., Ph.D., focuses on neuroimmune cell-mediated regulations of neuronal function, neurogenesis, neuroinflammation and neurodegeneration. Researchers in Dr. Ikezu's lab are particularly interested in how the innate immune-related cells, extracellular vehicles (EVs) and molecules in the central nervous system (CNS) influence the pathology and progression of select neurodegenerative disorders such as Alzheimer's disease (AD) and frontotemporal dementia.

Focus areas Gene therapy of AD. Dr. Ikezu's laboratory demonstrated the therapeutic effect of the CNS delivery of adeno-associated virus (AAV) expressing anti-inflammatory cytokines, dominant negative chemokines, and neurogenic factors for restoring hippocampal neurogenesis and memory function in mouse models of AD. Proteomic and biological characterization of EVs. The Molecular Neurotherapeutics Lab established the purification protocols of EVs from brain tissues, cerebrospinal fluid and plasma, and identified disease-specific protein markers by protein mass-spectroscopy and machine learning approaches using biospecimens from AD and chronic traumatic encephalopathy, animal models of AD, and human iPSC-derived neurons, astrocytes, microglia-like cells and oligodendrocytes. Researchers have also demonstrated the potent tau seeding activity of human AD brain-derived EVs on propagation of tau pathology after inoculation into aged mouse brains, suggesting the acceleration of tau pathology by EV secretion. Microglia and neuroinflammation. Dr. Ikezu and his colleagues also made substantial contributions to the classification of the activation phenotype of microglia, a cell type of significant interest. These microglial activation phenotypes were originally adapted from the M0, M1 and M2 classification of macrophages. However, more recent works on the characterization of the microglial gene expression phenotype in disease conditions show that microglia are largely in homeostatic or disease-associated states. The studies identified miR-155, APOE and TREM2 as key molecules for shaping the neurodegenerative microglia, which are also genetically associated with AD. Significance to patient care

Seminal work on the effect of CSF1R inhibitor on AD progression conducted by the Molecular Neurotherapeutics Lab stimulated the development and clinical trials of new CSF1R inhibitor on AD patients. In addition, Dr. Ikezu's invention on the cloning and functional characterization of TTBK1 leads this molecule as a new target of drug development for AD and related tauopathy.

Professional highlights Associate editor, Extracellular Vesicles and Cellular Nucleic Acids, 2020-present Editorial board member, Cells, 2020-present Senior section editor, Journal of Neuroimmune Pharmacology, 2016-present Editorial board, Archivum Immunologiae et Therapiae Experimentalis, 2013-present Standing member, Clinical Neuroimmunology and Brain Tumor study section, National Institutes of Health, 2018-2022 Named, Jack Spivack Distinguished Scientist in Neuroscience, Boston University School of Medicine, 2018 Recipient, Inge Grundke-Iqbal Award for Alzheimer's Research, Alzheimer's Association International Conference, 2016 Editorial board member, Journal of Neuroimmune Pharmacology, 2011-2016 Academic editor, PLoS One, 2009-2015 Recipient, Distinguished Scientist Award, University of Nebraska Medical Center, 2010 Recipient, UNeMed Research Innovation Award, 2009 Recipient, Vada Kinman Oldfield Alzheimer's Research Award, 2000

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