We want to know how kinases and phosphatases act on the myosin motor in muscle cells in relation to chemical second messengers controlling signaling networks.
We have established that smooth muscle requires myosin phosphorylation by a smooth muscle specific myosin light chain kinase. This phosphorylation is necessary for control of blood pressure by smooth muscle cells in blood vessels, movement of digested food in the stomach and intestines, maintenance of airways in the lungs, and emptying of the urinary bladder.
We have investigated interconnected chemical networks that affect myosin phosphorylation and using genetically modified mice with biophysical, biochemical and physiological measurements.
Primary hypotheses are directed to identifying the key signaling proteins essential for smooth muscle contraction that may contribute to the development of different smooth muscle based diseases, including our recent observation that mutations in the human gene of smooth muscle myosin light chain kinase caused aortic aneurysm and dissection.