Although they were unable to deliver their Award Lectures in person because of the 2020 Annual Meeting cancellation, the 2020 SOT Leading Edge in Basic Science Award recipient and Translational Impact Award recipient have recorded their respective Award Lectures, and these resources are now available for viewing on the SOT Video Library.
Lecturer: Wen-Xing Ding, University of Kansas Medical Center, Kansas City, KS.
In the 2020 Leading Edge in Basic Science Award Lecture, Dr. Ding discusses macroautophagy (hereafter referred to as autophagy), a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Autophagy is usually activated as a cellular adaptive/protective process and a quality control mechanism to maintain cellular homeostasis in response to an adverse environment, such as the deprivation of nutrients or exposure to toxic insults. Studies by the Ding laboratory revealed autophagy as a key protective mechanism against alcohol- and drug-induced liver injury by the selective removal of damaged mitochondria, protein adducts, excess lipid droplets, and drug metabolism cytochrome P450 enzymes. The Ding laboratory further demonstrated a critical role of mitochondrial dynamics in regulating mitophagy (a selective form of autophagy for removing mitochondria). Impaired/declined autophagy is closely associated with aging and contributes to liver tumorigenesis. Lysosomes sit at the end stage of autophagy via fusion with autophagosomes to form autolysosomes, where autophagic cargos are degraded. Studies of the Ding laboratory have identified that TFEB, a master transcription factor for lysosomal biogenesis, is impaired by alcohol and acetaminophen in the pancreas and liver, respectively, which promotes alcoholic hepatitis, pancreatitis, and drug-induced liver injury. Genetic and pharmacological activating autophagy and enhancing lysosomal biogenesis are promising approaches for preventing and reversing alcohol- and drug-induced tissue damage and fatty liver diseases.
Lecturer: David A. Jett, NIH Countermeasures Against Chemical Threats (CounterACT) Program and National Institute of Neurological Disorders and Stroke, Bethesda, MD.
In the 2020 Translational Impact Award Lecture, Dr. Jett discusses chemical poisonings. There are potentially thousands of toxic chemical exposures that pose a threat to public health. This threat is not hypothetical—toxic chemical exposures have occurred and continue to occur from industrial and common household accidents and from deliberate use in wars and terrorist attacks. Current events such as the use of chemical weapons in Syria and other parts of the world, alleged assassinations, and the precipitous rise of global chemical terrorism since 1970 are a reminder that chemical threats exist. Given the number of potential chemical threats to public health, there are surprisingly few true antidotes available for treating lethal and sublethal exposures. Current medical countermeasures primarily treat the symptoms, but often this is not sufficient because many chemical threats cause a complex array of short- and long-term effects that require careful management of symptoms in conjunction with true antidotes that target their mechanism of action. This lecture will describe the unmet need for antidote and therapeutic development for chemical threats and outline a multidisciplinary program developed at the National Institutes of Health designed to support translational research to address this need.
Dr. Jett was interviewed for 2022 SOT TV during the SOT 61st Annual Meeting and ToxExpo, discussing the development of a drug to treat seizures cause by everything from epilepsy to nerve agent exposure. To learn more, watch Dr. Jett’s SOT TV interview.