The Heinzen Lab focuses on the genetic and genomic basis of epilepsy disorders, including analyses of the role of germline mutations, somatic mutations, and how regulation of the cellular transcriptome influences the risk and presentation of seizures.
A current area of concentration is studying the role of somatic mutations in epilepsy and other neurological diseases. Unlike inherited variation or newly acquired mutations in parental gametes that present in the germline of offspring, mutations can also be acquired somatically at some point in development after fertilization. The burden and localization of a somatically acquired mutation depends on when each mutation arises. There is accumulating evidence that new mutations can lead to disease, and in some cases, severe tissue-specific disease. Dr. Heinzen’s lab currently has active research projects seeking to identify disease-causing somatic mutations in patients with brain malformations and in patients who have drug-resistant non-lesional focal epilepsy. This research led to the identification of somatic SLC35A2 variants in intractable neocortical epilepsy. Building from this discovery, the group now also has a research program that uses induced pluripotent stem cell derived neurons to study effects of somatic SLC35A2 variants on neural development and activity and explore novel treatment approaches for this form of genetic epilepsy.
The Heinzen lab also studies the transcriptome in brain tissue of epilepsy patients to better understand how regulation at this level may cause or contribute to the presentation of epilepsy. Making use of therapeutically excised tissue specimens from patients with a range of refractory epilepsies, the lab uses a variety of experimental approaches to study the tissue and cellular transcriptome and subsequently relate transcriptional changes to pathological endpoints.