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One or more keywords matched the following properties of Lemasters, John
overview I have a long-standing interest in hepatic ischemia-reperfusion (IR) injury, especially as it relates to organ preservation for transplantation. I and my colleagues were the first to show a prominent role for nonparenchymal cells in IR injury to cold-stored livers. Specifically, we showed that reperfusion after cold ischemic storage leads to killing of sinusoidal endothelial cells and activation of Kupffer cells. We were also pioneers in showing that onset of the mitochondrial permeability transition (MPT) then developed in hepatic parenchymal cells, leading to hepatic apoptosis, necrosis and graft failure, and we developed a variety of stratagems to ameliorate these injuries that are beginning to find clinical application. Overall, my laboratory has published over 350 papers in peer-reviewed journals plus more than 100 book chapters. Productive, long-term collaborations with both junior and senior colleagues contributed importantly to this success. My research interests continue to relate to mitochondrial and cellular bioenergetics, including studies of oxidative phosphorylation in isolated mitochondria, mitochondrial dysfunction in toxic, and hypoxic and reperfusion injury to liver and heart cells, and graft failure from preservation injury to livers stored for transplantation surgery. Our in vitro and in vivo studies of living cells and tissues have shown that mitochondrial calcium uptake, iron translocation from lysosomes to mitochondria, and oxidative stress promote the MPT. The MPT initially induces lysosomal degradation of mitochondria by autophagy, a selective process called mitophagy. However, excess MPT induction induces both necrotic cell death from ATP depletion and apoptosis due to cytochrome c release after mitochondrial swelling. For these projects, my laboratory extensively applies new techniques of quantitative laser scanning confocal and intravital multiphoton microscopy for physiological analysis of single cells and living organs. The lab also extensively employs Seahorse technology to measure respiration and glycolytic flux in cultured cells. Current projects are examining how iron mobilization from lysosomes to cytosol and then to mitochondria during cold ischemic liver storage sensitizes hepatocytes and nonparenchymal cells to adverse events after reperfusion, leading ultimately to injury and failure of liver grafts. Despite a detailed understanding of their metabolism, mitochondria often behave anomalously. In particular, global suppression of mitochondrial metabolism and metabolite exchange occurs in apoptosis, ischemia/hypoxia, alcoholic liver disease and aerobic glycolysis in cancer cells (Warburg effect). My lab is also examining and supporting the novel hypothesis that closure of voltage-dependent anion channels (VDAC) in the mitochondrial outer membrane accounts for global mitochondrial suppression consistent with a role for VDAC as a dynamic regulator, or governator, of global mitochondrial function both in health and disease. In cancer cells, we showed that free tubulin causes closure of VDAC.
One or more keywords matched the following items that are connected to Lemasters, John
Item TypeName
Academic Article Evidence that Carolina rinse solution protects sinusoidal endothelial cells against reperfusion injury after cold ischemic storage of rat liver.
Academic Article Ischemic preconditioning of rat livers against cold storage-reperfusion injury: role of nonparenchymal cells and the phenomenon of heterologous preconditioning.
Academic Article Carolina rinse solution minimizes kidney injury and improves graft function and survival after prolonged cold ischemia.
Academic Article Reperfusion injury to endothelial cells following cold ischemic storage of rat livers.
Academic Article Increase in survival of liver grafts after rinsing with warm Ringer's solution due to improvement of hepatic microcirculation.
Academic Article Reperfusion rather than storage injury predominates following long-term (48 h) cold storage of grafts in UW solution: studies with Carolina Rinse in transplanted rat liver.
Academic Article Evidence that activation of Kupffer cells increases oxygen uptake after cold storage.
Academic Article Amino acids in storage solution predict primary nonfunction in fatty liver grafts.
Academic Article Carolina rinse solution--a new strategy to increase survival time after orthotopic liver transplantation in the rat.
Academic Article Evidence that graft survival is not related to parenchymal cell viability in rat liver transplantation. The importance of nonparenchymal cells.
Academic Article Selective loss of nonparenchymal cell viability after cold ischemic storage of rat livers.
Academic Article Reperfusion injury to endothelial cells after cold storage of rat livers: protection by mildly acidic pH and lack of protection by antioxidants.
Academic Article Role of sinusoidal lining cells in hepatic reperfusion injury following cold storage and transplantation.
Concept Cold Temperature
Search Criteria
  • Cold Temperature