Focus 1. Determine if cardiac cellular energetics are compromised in epilepsy models. Several diseases have been linked to altered mitochondrial function, including diabetes, cardiovascular disease, and neurodegeneration. In the brain and heart, ATP demand is high, as it is necessary for efficient cell signaling in addition to maintaining ionic homeostasis. We hypothesize that compromised mitochondrial energetics may precede and/or underlie cardiac arrhythmias, cell death, and epileptic events. Instability in mitochondrial membrane potential (ΔΨm) is linked to alterations in cellular excitability, and the ability of the mitochondria to match supply and demand for ATP is crucial for proper cellular function.
3 separate projects are currently ongoing in this focus. The first project is focused on determine the role of cardiac arrhythmias in Dravet Syndrome (a pediatric epilepsy). The second project seeks to determine how mitochondrial energetics alter neuronal excitability in models of Temporal Lobe Epilepsy. A third project seeks to determine the role of mitochondria in the neurodegenerative processes and development of seizures following Traumatic Brain Injry.
Focus 2. Determine the role of dihydroorotate dehydrogenase (DHODH) in cardiac function and ischemia-reperfusion injury. Our work has demonstrated the inhibition of DHODH increases damage during a myocardial infarction (heart-attack). This project seeks to elucidate the role of DHODH in the heart, with the hope of uncovering novel therapeutic targets to decrease tissue damage.
Focus 3. Elucidating the role of VGSC β-subunits on K+ channel trafficking, expression and, formation of macromolecular complexes. The voltage-gate sodium channel β subunits are multifunctional, developmentally regulated, immunoglobulin superfamily cell adhesion molecules and ion channel modulators that play critical roles in cellular excitability. Mutations are linked to several cardiovascular diseases, including atrial fibrillation and Brugada syndrome. Additionally, Scn1b deletion results in a severe seizure and SUDEP phenotype in mice with modulation of Na+ and K+ currents in brain as well as Na+ currents in heart. Understanding the effect that loss of these β subunits has on repolarizing KV current is important to fully understand how the β subunits affect neuronal and cardiac excitability.
Focus 4. Determining the link between cardiac biomarkers and perceptions of well-being in Appalachian area K-12 teachers. The K-12 educator workforce population is shrinking, with many educators stating concerns of their well-being as a top reason for leaving. This project seeks to determine if we can identify novel research measures and methods to link with perceptions of educator well-being. It is our hope that the results from this project can lead to an improved ability to identify those likely to leave the workforce over concerns of well-being and inform interventions in underserved rural Appalachia.