Lipid control of ion channel gating
Lipids are the most intimate ligand any channel sees. With purified channel proteins, we can combine crytstallography and functional analyses to determine the molecular nature and consequencesa of specific lipid interactions.
Single molecule FRET
To bridge single molecule function (i.e. single channel currents) and single molecule structure (by high resolution crystallography or cryo-EM approaches) we have developed smFRET to measure intra-molecular distances in real time, in membrane embedded ion channels.
Vascular consequences of KATP gain-of-function
CS patients show complex vascular totuosity and dilation. To model CS we have engineered unique transgenic and knock-in animal models. These animals show low blood pressure and vascular relaxation.
Cantu Syndrome – cardiac consequences of KATP gain-of-function
Surprisingly, CS patients show enlarged and hypercontractile hearts. Unique transgenic CS animals also show enlarged and hypercontractile hearts – explained by vascular-cardiac feedback.
Modeling excitability-dependent diabetes in zebrafish
Approaches to isolate and record electrical activity in zebrafish pancreatic islets show us that zebrafish beta cells contain the same KATP channels as mammals and exhibit similar KATP-dependent glucose tolerance, providing a model organism to study insulin secretion and glucose handling.
iPSC-derived cardiovascular tissues
To pursue human cell specific consequences of Cantu Syndrome and other diseases, we are establishing protocols to generate cardiac and vascular myocytes. Figure shows smooth muscle actin expression and pinacidil- and glibenclamide-sensitive currents, in human iPSC-derived smooth muscle cells.