Steven J. Sollott, MD
The Cardioprotection Unit studies structure and function of cells from the cardiovascular system along two principal lines: (1) Nature and control of mitochondrial instability and cell death during oxidant stress, and protection of cardiac myoctes (and neurons) during ischemic stress; and (2) Cellular changes and vascular protection after vascular injury. Recent work lead to the discovery of a novel phenomenon accompanying induction of the mitochondrial permeability transition (MPT) in cardiomyocytes, termed “ROS induced ROS release”. This lead to the identification of the mechanism by which ischemia/reperfusion injury damages mitochondria, as well as the mechanism of cardioprotection afforded by ischemic preconditioning. Research proved that the MPT is the end effector in these processes: the threshold for MPT induction by ROS being significantly reduced after ischemia reperfusion, but beneficially increased by preconditioning. The general mechanism of protection against oxidant stress damage was shown to be the convergence of more than one dozen distinct protection signaling mechanisms via inhibition of GSK 3beta on the end effector, the permeability transition pore complex, to limit induction of the MPT. Signaling defects underlying the age associated loss of the capacity for ischemic preconditioning are being examined which could lead to testable clinical therapies relevant to the preservation of healthy aging. His research together with a colleague, Jim Kinsella, was the first to demonstrate that the anti tumor drug, paclitaxel (Taxol), could have clinical promise to prevent vascular restenosis, leading to clinical trials worldwide. Drug eluting stents have become a primary treatment of coronary artery disease, and paclitaxel is one of only two drugs applied to stents that have been shown to safely and effectively reduce the incidence of restenosis in humans. Paclitaxel eluting stents currently comprises ~70% of the drug eluting stents utilized worldwide. My lab is interested in novel strategies for vascular protection.