Jack M. George Chair in Medicine
Division of Cardiovascular Medicine
Division of Endocrinology
Director, Translational Research,
Dorothy M. Davis Heart and Lung Research Institute
and Diabetes and Metabolism Research Center
BA: University of Chicago, Chicago, IL
PhD: University of Texas Southwestern Medical School, Dallas TX
My research program investigates the metabolic basis of impaired contractile function in the diseased heart and the impact of altered cardiac metabolism on peripheral organs and systemic metabolism. A particular focus is the metabolic basis of heart failure, exploring maladaptive metabolic adaptations to pathological and metabolic stress on the heart, and the metabolic consequences of heart failure on the whole body. Active research protocols assess genomic, transcriptional and post-translational regulation of metabolic flux in the heart under normal physiological conditions and pathophysiological states such as overload induced heart failure, diabetic cardiomyopathy, and ischemia/reperfusion.
A hallmark of the research program of the this multidisciplinary laboratory effort is the application of NMR and stable isotope kinetics, combine with mass spectrometry, to quantify metabolic flux through pathways and single enzymes, intracellular transport rates of metabolic intermediates across cellular membranes, and metabolic turnover within the intact beating heart. With these experimental approaches we are able to visualize and quantify metabolic activity during full hemodynamic monitoring of cardiac function in both normal and diseased hearts. Experimental outcomes elucidate fundamental mechanisms of disease and identify potential therapeutic targets within the cardiomyocyte. Potential therapeutic protocols are then tested by manipulating metabolic activity in the ailing heart with both pharmacological support and targeted induction or suppression of metabolic genes.
Combined with investigation of metabolic changes in the myocardium of patients with clinical heart failure, we are able to implement a translational approach that integrates a mechanistic and predictive understanding from basic science experiments with clinical research protocols. Recent studies have elucidated inefficiencies in carbohydrate metabolism and mitochondrial function in failing and diabetic hearts. We have also identified mechanisms of impaired lipid uptake and storage dynamics and downstream fatty acid metabolism that lead to impaired transcriptional regulation of metabolic gene activation, formation of intracellular lipotoxic intermediates, and compromised energy metabolism in cardiac mitochondria.
Our laboratory has been continually funded by the NIH for over two decades and Dr. Lewandowski is a recipient of the MERIT Award (R37) from the National Heart, Lung and Blood Institute of the NIH and an Established Investigator Award from the American Heart Association. He has also been elected a Fellow of the International Society for Heart Research (ISHR) and a Fellow of the American Association for the Advancement of Science (AAAS).