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NOBEL PRIZE 2026

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NIHNATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKER01

Decoding the cellular and molecular mechanisms of epileptogenesis and disease progression in mTORopathies

Active
Institution
UNIVERSITY OF MICHIGAN AT ANN ARBOR, MI
Principal investigator
Yu Wang
Funding
$519K
Duration
2024–2029
Open portfolio

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Abstract

ABSTRACT mTORopathies, such as focal cortical dysplasia type II (FCDII), is the most common underlying pathology in children with drug-resistant epilepsies. However, the underlying mechanisms of epileptogenesis, hyperexcitability, and disease progression remain largely elusive. In this proposal, we combine animal models and resected human tissues to understand the cellular and molecular logic networks in the dysplastic cortex. We use cutting-edge technologies in molecular genetics, electrophysiology, transgenics, and RNA sequencing to provide conceptual insights broadly relevant to understanding mTOR-related epilepsies. Our central hypothesis is that a sustained neurotoxic microenvironment mediated by complement component C3 progressively sculpts cellular and molecular architectures, impair cortical inhibitory circuits, and promote epileptogenicity in the malformed cortex.

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R01NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKEDevelopmental Brain Disorders Study Section[DBD]cortexcorticalepileptogenesishyperexcitabilitydisease progressionresectedcellular molecularunderstand cellular

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