The Department of Neurology has investigators active in both basic and clinical research in epilepsy. Current clinical research involves investigational epilepsy drug trials, clinical genetics, fMRI imaging, as well as epilepsy surgery. The epilepsy surgical director, together with clinical engineering, recently received a $3 million NIH grant for epilepsy research.
Clinical trials in epilepsy are focused on controlling seizures in patients with drug-resistant epilepsies. See below for details on current and upcoming trials.
Faculty members in the Epilepsy Division regularly receive funding from such institutions as the National Institutes of Health and others.
Faculty members in the Epilepsy Division are leading research in the following areas:
Clinical treatments in epilepsy
Dr. Abou-Khalil’s research interests are predominantly in the area of clinical epilepsy, including seizure semiology, anti-seizure medications, epilepsy surgery, development of new therapies for epilepsy, and clinical epilepsy genetics.
He has conducted numerous trials of experimental and new antiepileptic drugs in various forms of epilepsy. Drugs being investigated include cenobamate, padsevonil, esclicarbazepine and brivaracetam for refractory focal-onset seizures.
Dr. Haas’s clinical research projects focus on epilepsy surgery, ICU-EEG monitoring, epilepsy genetics, and status epilepticus. He is the Vanderbilt site principal investigator for the Critical Care EEG Consortium. In addition, he currently serves as the site principal investigator for multiple clinical trials evaluating new antiepileptic drugs and devices for diagnosis and treatment of medication-resistant epilepsy.
GABA receptors and epilepsy drugs
Dr. Macdonald’s laboratory is focused on understanding the structure and function of recombinant and native gamma aminobutyric acid (GABA) type A (GABAA) receptor channels, and the basic mechanisms of epilepsy and anticonvulsant drugs. GABAA receptor channels are the major inhibitory neurotransmitter receptors in the brain. Reduction of GABAA receptor function produces seizures and epilepsy in animals and man, and enhancement of GABAA receptor function has been used to treat seizures. At least four forms of human epilepsy have been linked to mutations in the alpha1 and gamma2 GABAA receptor subunits. The mechanisms for neurotransmitter activation, regulation of the opening and closing (gating), desensitization and intracellular trafficking of these channels are unknown.
Sudden death in epilepsy
Dr. Nobis' research focuses on sudden unexplained death in epilepsy (SUDEP), in particular electrophysiological and targeted functional anatomical evaluation of extended amygdala circuits relation to seizures and respiratory control. He hopes that a translational and basic science approach will be broadly applicable to sudden death via neurologic mechanisms such as SUDEP and SIDS and that these brain regions can be explored in terms of their potential role in comorbid depression and anxiety often seen in epilepsy patients.
For more information on Dr. Nobis’ research, visit his lab website.
Tuning of inhibitory neurotransmission in epilepsy
Dr. Lagrange’s lab uses electrophysiological techniques with brain slices and immortalized cultured cells to study the tuning of inhibitory neurotransmission during normal brain function and in disease states, including epilepsy. GABA is the primary inhibitory neurotransmitter in the adult brain and is critical for normal brain function. However, in the developing brain, GABA acts as an excitatory signal that directs normal neuronal migration and synaptogenesis. Dr. Lagrange’s lab has found that a predominant GABA receptor expressed primarily during early life is subject to RNA editing in a developmentally regulated fashion. By introducing a single amino acid change in a key portion of these GABA receptors, RNA editing leads to significant changes in receptor function, thereby producing a brief window in late embryogenesis/early postnatal life in which GABA causes the prolonged/slow depolarizations that are important for the subsequent formation of both excitatory and inhibitory connections later in life.
Read more about Dr. Lagrange’s research at his lab website.
Brain sleep-state and seizure onset
Dr. Zhou’s interests in basic neuroscience and translational medicine focus upon how neuronal activity within the whole brain circuits (both cortical and subcortical circuits on microscopic, mesoscopic and macroscopic levels) interacts to generate collective/emerging brain functions such as memory consolidation and brain disorders such as seizures and cognitive co-morbidity deficits. Particularly he is working on how brain sleep-states intermingle with seizure onset. Using electrophysiological recordings, optogenetic methods, and transgenic mice with GABAergic receptor mutations, he studies intrinsic neuron activity properties, activity-dependent synaptic plasticity in cortical neurons from mouse models for pathogenesis of idiopathic generalized epilepsy (IGE), and explores how epilepsy disorders and memory deficits are generated/evolved.
Read more about Dr. Zhou’s research at his lab website.
Gene mutations in epilepsy syndromes
Dr. Kang is interested in understanding the pathophysiology of GABAA receptor gene mutations in various epilepsy syndromes including Dravet syndrome. Dr. Kang’s current research centers around using patient derived induced pluripotent stem cells (iPSCs) and genetically modified mouse models to understand the role of GABAA receptors and GABA transporters in normal development and diseased conditions especially epilepsy and treatment development.
Epilepsy genes and environmental factors
Dr. Gallagher’s main research interest is the elucidation of the interactions between epilepsy genes and environmental factors, such as traumatic brain injury, that promote the formation of epileptic circuits and that inhibit the normal functioning of cognitive networks. He uses electrophysiological techniques coupled with advanced signal processing analyses to interrogate the networks and then employs molecular and electrical neuromodulation approaches to restore normal neurophysiological functioning.
Computational analysis in neurologically impaired states
Dr. Williams Roberson’s research interests center around elucidating the neurophysiologic signal characteristics underlying consciousness and cognitive functions such as language production, perception and memory, and the use of these features to optimize the care of patients with central nervous system disorders such as delirium, dementia, epilepsy, and stroke. She applies computational and quantitative analysis techniques toward elucidating the neurophysiological basis of cognitive functions in health and in neurologically impaired states.
GABAA receptor mutations in epilepsy
Dr. Qu’s research is focused on the mechanisms of epilepsy caused by mutations in GABAA receptors by using engineered mouse models harboring mutations from epilepsy patients. They also use these models to evaluate antiepileptic drugs and develop new therapeutics.
Actively recruiting trials
Trials expected to start recruiting shortly
OPC-214870 effect on photic-induced paroxysmal electroencephalogram responses (ClinicalTrials.gov Identifier: NCT04241965)
CVL-865 for drug-resistant focal onset seizures (ClinicalTrials.gov Identifier: NCT04244175)
For more information on clinical trials, contact Melissa Osborn, RN- Study Coordinator at (615) 322-8817 or send an email to firstname.lastname@example.org.