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

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $562,313

## 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.

## Key facts

- **NIH application ID:** 10851506
- **Project number:** 1R01NS136181-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Yu Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $562,313
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10851506

## Citation

> US National Institutes of Health, RePORTER application 10851506, Decoding the cellular and molecular mechanisms of epileptogenesis and disease progression in mTORopathies (1R01NS136181-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10851506. Licensed CC0.

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