# Modeling genetic risk for epilepsy using IPSC and animal models.

> **NIH NIH K08** · JOHNS HOPKINS UNIVERSITY · 2021 · $199,260

## Abstract

Project Abstract
 This proposal describes a mentored career development plan and research proposal that is designed to
facilitate my transition to becoming an independent clinician scientist with specialization in the genetic
determinants of epilepsy and underlying molecular mechanisms of epileptogenesis. Epilepsy affects 1% of the
population and results in significant morbidity. Despite increasing discoveries of genetic etiologies that increase
epilepsy susceptibility, this information has not led to disease modifying treatments. A better understanding of
the mechanisms of epileptogenesis as a result of genetic changes may bring us closer to developing disease
modifying treatments. Alterations in intrinsic cell excitability, neuronal organization and synaptic function are
potential mechanisms leading to increased network excitability seen in epilepsy. Deletion of the 15q11.2 locus
is found in 1.4% of genetic epilepsies, making it one of the most common susceptibility loci identified to date
and it results in haplo-insufficiency of the CYFIP1 gene. The CYFIP1 gene regulates activity dependent
translation at excitatory synapses as well as dynamic actin rearrangements required for normal neurogenesis
and synaptic development. I hypothesize that increased seizure susceptibility and neuropsychiatric disorders in
patients with 15q11.2 CNV results from alterations in CYFIP1 expression. In this application, I propose a
research plan that will evaluate the functional consequences and underlying mechanisms of CYFIP1-mediated
changes using a combination of in vitro human iPSC and in vivo mouse models. My mentorship team includes
Nicholas Maragakis, Dwight Bergles, and Carl Stafstrom at Johns Hopkins University and Hongjun Song at the
University of Pennsylvania. I have identified 4 short term training goals and 2 long term goals for this funding
period. My short term goals are to (1) develop in vitro humanized models to validate molecular mechanisms of
epilepsy and excitation / inhibition (E/I) imbalance in the context of human genetic backgrounds; (2) develop
and manipulate animal models to probe epilepsy susceptibility and E/I imbalance (3) receive training in
advanced electrophysiological techniques, and (4) improve my skills in statistically sound experimental design
and analysis. My long term goals are to (1) develop an independent research career investigating the
mechanisms of epilepsy in the wider context of neurodevelopmental disabilities and (2) further develop a
clinical niche in the care of patients with genetically determined epilepsy. My career development plan and
mentorship team will allow me to achieve these goals. The research plan will establish complementary in vitro
and in vivo model systems to investigate underlying mechanisms, screen for therapeutic interventions and
develop a platform that is generalizable to the investigation of other genetic risk factors for epilepsy. These
studies will provide a foundation for my R01 submission in...

## Key facts

- **NIH application ID:** 10197233
- **Project number:** 5K08NS102526-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Christa Habela
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $199,260
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197233

## Citation

> US National Institutes of Health, RePORTER application 10197233, Modeling genetic risk for epilepsy using IPSC and animal models. (5K08NS102526-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10197233. Licensed CC0.

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