Molecular mechanisms of epileptogenesis in tuberous sclerosis complex.

This is an ongoing project.

Faculty Researcher: Alan Dombkowski

Contact Details

Alan Dombkowski


Tuberous sclerosis complex (TSC) is a genetic disorder that occurs in approximately one of every 6,000 live births. Germline mutations are found in the TSC1 or TSC2 genes in 80% of TSC patients. The major clinical manifestation of TSC is the prevalence of hamartomatous lesions that can develop in a variety of organs. Brain lesions (tubers) occur in 90-95% of TSC patients and contribute to a range of neurological disorders, including epilepsy, autism, and other cognitive and behavioral impairments. Epilepsy afflicts up to 90% of TSC patients and many suffer intractable seizures that do not respond to pharmacological therapy. Epileptic foci are usually associated with cortical tubers in TSC, although not all tubers are epileptogenic. It is unknown why some tubers are epileptogenic, while others are not. We are studying molecular contributors to the epileptogenic potential of tubers using cortical tissue that was resected from TSC patients to treat intractable epilepsy. We use genomic technology, including next generation sequencing (Ion Torrent) and microarrays, to characterize gene expression, microRNAs, mutations, and epigenetic modifications that contribute to the epileptogenic potential of cortical tubers. The outcomes of this research are expected to expand our understanding of the epilepsy in TSC, identify novel therapeutic targets, and improve diagnostic imaging methods.


Students with experience and/or interest in any of the following are encouraged to inquire:

RNA and protein isolation/purification
Western blot
Cell culture
Luciferase reporter assays
Chromatin immunoprecipitation
Next generation sequencing

Project Timeline

This is an ongoing project with funding support anticipated through March, 2017.


Depending on the student's interests and skills, participation in the following activities may be available:

Quantify microRNA expression in human tissue and/or cell lines using RT-PCR, microarrays, and/or next-generation sequencing.

Characterize the effect of microRNA expression on target genes using luciferase reporter assays.

Investigate genomic mutations and/or epigenetic modifications using PCR and/or next-generation sequencing.

Develop computer applications for the analysis of genomics data.

This project has considerable potential to offer students the opportunity to contribute research that may warrant co-authorship on peer-reviewed publications.

Project-related Tags

Last Updated

February 12, 2014