# The Role of STRADA in Epileptogenesis and Brain Malformations

> **NIH NIH K08** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $176,762

## Abstract

Project Summary
This proposal describes a five-year career development program designed to lead the PI to a career as an
independent clinician scientist in translational neuroscience, studying mechanisms by which genetic mutations
result in abnormal neurodevelopment and epilepsy.
Applicant: The applicant holds M.D. and Ph.D. degrees and has completed specialty training in Child
Neurology as well as Epilepsy/Clinical Neurophysiology. He has previous experience in neuroscience research
using mouse models to study embryonic forebrain development. The career development plan includes a
period of mentored research designed to develop the applicant's knowledge in advanced imaging techniques,
electrophysiology, transcriptomics, and bioinformatics. This will greatly enhance his existing training and allow
him to develop as an independent investigator. The applicant will hone his scientific skills through the proposed
research by meetings with his mentor and collaborations with the members of his advisory committee. He will
learn research techniques through formal coursework, journal clubs, lab meetings, seminars, and national
meetings. The training plan will also include workshops to develop grant writing skills and didactic training in
the responsible conduct of research. These opportunities will allow the applicant to develop the conceptual and
technical toolbox needed for an independent career in a clinically important field of study.
Research Plan: Epilepsy is a major cause of morbidity, mortality, disability, and expense, and affects 470,000
children in the U.S. While many medications to control seizures have been developed, about 30% of patients
do not respond to medications, and to date, there are no medications that can prevent or halt the progression
of epilepsy. Recently, many genetic causes of epilepsy have been identified, providing insights into pathways
involved in epileptogenesis. Mutations causing hyperactivity of the mTOR pathway (so-called “mTORpathies”)
have emerged as an important cause of cerebral malformations and epilepsy, including tuberous sclerosis
complex, focal cortical dysplasia, and polyhydramnios, megalencephaly, and symptomatic epilepsy (PMSE)
syndrome, which is caused by a homozygous loss-of-function in the STRADA gene. This proposal will test the
central hypothesis that loss of STRADA causes cortical malformation and epilepsy by promoting retention of a
neural stem cell identity, delaying neuronal differentiation, and increasing synaptic neuronal hyperexcitability.
This innovative proposal will use human cortical organoids, 3-D neural structures that resemble the developing
cortex, to determine the effect of STRADA mutations on early cortical development (Aim 1), neuronal
excitability (Aim 2), and cell-type specific transcriptional changes (Aim 3). This study will provide a platform to
develop mechanistically driven therapies that can halt or reverse epileptogenesis for mTORopathies, and our
findings should be applicable...

## Key facts

- **NIH application ID:** 9990875
- **Project number:** 5K08NS109289-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Louis Tuong Chinh Dang
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $176,762
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9990875

## Citation

> US National Institutes of Health, RePORTER application 9990875, The Role of STRADA in Epileptogenesis and Brain Malformations (5K08NS109289-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9990875. Licensed CC0.

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