Having a sister who has struggled with seizures since the age of six months, Romela Petrosyan hoped to find a research group where she could gain more insight about her sister’s disorder and was ecstatic to be accepted into Dr. Baram’s laboratory. The ultimate goal of the lab is to build a clear understanding of the mechanism of epileptogenesis from febrile seizures, which will allow for new medical means to counter the development of epilepsy. Romela is thrilled to be a part of discovering ways to help the countless people who suffer from this disorder, and she plans to continue her education through medical school, eventually becoming a physician.

Epilepsy is a devastating disorder that affects millions of people worldwide. One of the most common types of epilepsy, temporal lobe epilepsy (TLE), is associated with significant morbidity in cognitive and psychosocial dysfunction. TLE has long been correlated with a history of childhood febrile seizures; hence, understanding the consequences of febrile seizures on TLE is of considerable clinical significance. The Baram laboratory has consistently observed downregulation after seizures of the Hyperpolarization Activated Cyclic-Nucleotide Gated 1 (HCN1) channels that are responsible for mediating hyperpolarization-activated (Ih) currents. In the hippocampus, these currents regulate the resting membrane potential, shape rhythmic and synchronized neuronal activity, and regulate the temporal summation of dendritic depolarization. This study targets the factors responsible for regulating the transcription of the HCN1 gene. By using Chromatin Immunoprecipitation, polymerase chain reaction, and DNA electrophoresis, we show that the neuron restrictive silencer factor (NRSF) binds to the NRSE region in the first intron of the HCN1 gene. NRSF, in conjunction with its cofactors, deacetylates and methylates the chromatin, preventing transcription of the HCN1 gene. Such biochemical change may produce neuronal injury to the developing brain, promoting the onset of epilepsy.

Tallie Z. Baram School of Medicine

Epilepsy is the most common brain disorder of young people, but the mechanisms that convert a normal brain into an epileptic one are unknown. Sometimes, infection or injury can kill brain cells or injure them; however, when epilepsy begins early in life, there is often no evidence of injury. Romela examined the possibility that in response to specific insults, there are “maser switches” that attach to genes within neurons and change their expression, modifying how neurons act. She focused on NRSF and found massive increase in its binding to DNA of several important neuronal genes, leading to loss of proteins encoded by these genes and perturbing the ability of neurons to communicate. Romela’s project provides a mechanism for the conversion of a normal brain into a diseased one, and hopefully points toward a means of reversing the process.