The laboratory studies the physiology, regulation and biophysics of potassium (K+) channels. These membrane proteins modulate the activity of excitable cells and shape signaling events in non-excitable cells such as hormone and transmitter release. We employ a multidisciplinary approach that integrates techniques such as molecular biology, biochemistry, genetics, optical imaging and electrophysiology. We study K+ channels in two general systems: the genetically tractable worm Caenorhabditis elegans and mammalian heterologous expression systems in which cDNA clones of channels can be studied background-free, under controlled experimental conditions. This approach enables us to bridge in the same organism, genes, proteins, and behavior. We are currently pursuing three areas of research:
Oxidation of K+ channels and neurodegeneration
One theory of aging, the free-radical theory, posits that organisms age because cells accumulate highly reactive, and therefore potentially toxic—molecules known as reactive oxygen species or ROS. Bearing an umpaired electron ROS can oxidize a variety of cellular components causing significant cellular damage. Current projects are aimed at understanding how ROS-mediated oxidation of K+ channels impact the progressive decline in neuronal function which is part of the normal aging process and neurodegenerative disease such as Alzheimer's.
K+ channels and learning
We recently identified a K+ channel complex, termed KHT-1-MPS-1, homolog to mammalian Kv3.1-KCNE2, which is key to a simple, yet fundamental, form of learning: habituation. Current projects focus on identifying key genes that regulate the expression/trafficking of this channel complex.
A primitive heart model
Mammalian hearts evolved from primitive pumps that appeared more than 500 millions years ago. More recent developments incude peristaltic pumps in Drosophila and in C. elegans (pharynx). We have begun to develop the pharynx of C. elegans into a simple model of the heart. Current projects are aimed at identifying aging genes that protect the function of the pharynx during aging.