KCNQ2 and KCNQ3 variants in neuronal physiology

Currently over 100 KCNQ2/3 pathogenic variants have been associated with epileptic encephalopathy. Studies in heterologous cells indicate that these loss-of-function and gain-of-function mutations impact different aspects of KCNQ channel physiology including their voltage-sensitivity, surface expression, and PIP2 affinity. We are examining whether different mutations can lead to similar neurophysiological phenotypes by introducing KCNQ2 and KCNQ3 channels with encephalopathy-associated mutations into cortical neurons using in utero electroporation and also generate Kcnq2 knockin mice carrying KCNQ2 encephalopathy mutations.

KCNQ channels and breathing

In collaboration with Dr. Mulkey, University of Connecticut.

Sudden Unexpected Death in Epilepsy (SUDEP) has been previously associated with cardiorespiratory defects. Currently, its unknown whether seizures lead to increased excitability at brainstem breathing centers. As such, we are investigating the role of KCNQ2/3 dysfunction in respiration, and whether cortical seizures can lead to respiratory defects.