Positions

Overview

  • Since 2000, Dr. Wende has explored the regulation of metabolism and mitochondrial function with a specific focus on glucose utilization in heart and muscle. After completing his undergraduate biochemistry degree and an Honors Thesis with Dr. Mark R. Brodl at Knox College in Galesburg, IL he went on to undertake his Ph.D. training in the Cardiology Department as part of the Division of Biology and Biomedical Sciences at Washington University in St. Louis, MO studying transcriptional regulation with Dr. Daniel P. Kelly. After completing his thesis work in the spring of 2006, he joined the University of Utah to pursue his postdoctoral studies with Dr. E. Dale Abel examining upstream regulation by cellular signaling and the resulting changes in mitochondrial physiology. Then in August of 2013, he joined the faculty at The University of Alabama at Birmingham in the Division of Molecular and Cellular Pathology as an Assistant Professor. His work has been funded by the American Heart Association, the JDRF, and most recently by an NIH R01 award. With these training experiences he has expanded his independent research program through use of transgenic and diabetes mouse models to identify molecular and genetic mechanisms of glucose-mediated control of mitochondrial function. His outside interests include time with his wife and two daughters and running marathons.
  • Selected Publications

    Academic Article

    Year Title Altmetric
    2019 DNA methylation reprograms cardiac metabolic gene expression in end-stage human heart failure 2019
    2019 Novel role of the ER/SR Ca2+ sensor STIM1 in the regulation of cardiac metabolism 2019
    2019 Epigenetics in the development of diabetic cardiomyopathy 2019
    2019 Genome-wide DNA methylation encodes cardiac transcriptional reprogramming in human ischemic heart failure 2019
    2019 Mitoquinone ameliorates pressure overload-induced cardiac fibrosis and left ventricular dysfunction in mice 2019
    2019 The Growing Case for Use of SGLT2i in Heart Failure: Additional Benefits of Empagliflozin in a HFpEF Rodent Model 2019
    2019 Resident macrophages reprogram toward a developmental state after acute kidney injury 2019
    2019 Prolactin receptor signaling regulates a pregnancy-specific transcriptional program in mouse islets 2019
    2019 The SETD6 Methyltransferase Plays an Essential Role in Hippocampus-Dependent Memory Formation 2019
    2018 Glucagon receptor signaling regulates energy metabolism via hepatic farnesoid X receptor and fibroblast growth factor 21 2018
    2018 Antiretroviral therapy potentiates high-fat diet induced obesity and glucose intolerance 2018
    2018 Temporal partitioning of adaptive responses of the murine heart to fasting 2018
    2018 Mitochondrial Reactive Oxygen Species in Lipotoxic Hearts Induce Post-Translational Modifications of AKAP121, DRP1, and OPA1 That Promote Mitochondrial Fission 2018
    2018 Gene expression analysis to identify mechanisms underlying heart failure susceptibility in mice and humans 2018
    2017 Glucose transporter 4-deficient hearts develop maladaptive hypertrophy in response to physiological or pathological stresses 2017
    2017 Genetic disruption of the cardiomyocyte circadian clock differentially influences insulin-mediated processes in the heart 2017
    2017 Diabetes-related cardiac dysfunction 2017
    2017 Metabolic Origins of Heart Failure 2017
    2017 O-GlcNAcylation and cardiovascular disease 2017
    2017 My sweetheart is broken: Role of glucose in diabetic cardiomyopathy 2017
    2016 Redox biology and the interface between bioenergetics, autophagy and circadian control of metabolism 2016
    2016 Post-translational modifications of the cardiac proteome in diabetes and heart failure 2016
    2015 Phosphoinositide dependent protein kinase 1 is required for exercise-induced cardiac hypertrophy but not the associated mitochondrial adaptations 2015
    2015 Unsticking the broken diabetic heart: O-GlcNAcylation and calcium sensitivity 2015
    2015 Myocardial mitochondrial dysfunction in mice lacking adiponectin receptor 1 2015
    2015 Enhanced cardiac Akt/protein kinase B signaling contributes to pathological cardiac hypertrophy in part by impairing mitochondrial function via transcriptional repression of mitochondrion-targeted nuclear genes 2015
    2014 Intramuscular fat and inflammation differ in older adults: The impact of frailty and inactivity 2014
    2014 The absence of insulin signaling in the heart induces changes in potassium channel expression and ventricular repolarization 2014
    2014 Cardiomyocyte-specific BMAL1 plays critical roles in metabolism, signaling, and maintenance of contractile function of the heart 2014
    2014 GLUT1 deficiency in cardiomyocytes does not accelerate the transition from compensated hypertrophy to heart failure 2014
    2014 Insulin receptor substrates are essential for the bioenergetic and hypertrophic response of the heart to exercise training 2014
    2014 Intramuscular fat and inflammation differ in older adults: The impact of frailty and inactivity 2014
    2014 Maintaining PGC-1α expression following pressure overload-induced cardiac hypertrophy preserves angiogenesis but not contractile or mitochondrial function 2014
    2013 Insulin receptor substrate signaling suppresses neonatal autophagy in the heart 2013
    2013 APpEaLINg therapeutic target for obesity cardiomyopathy? 2013
    2013 Regulation of fatty acid metabolism by mTOR in adult murine hearts occurs independently of changes in PGC-1α 2013
    2013 Metabolic Determinants of Electrical Failure in Ex-Vivo Canine Model of Cardiac Arrest: Evidence for the Protective Role of Inorganic Pyrophosphate 2013
    2013 Regionalmuscle glucose uptake remains elevated one week after cessation of resistance training independent of altered insulin sensitivity response in older adults with type 2 diabetes 2013
    2013 Cardiac PI3K-Akt impairs insulin-stimulated glucose uptake independent of mTORC1 and GLUT4 translocation 2013
    2013 Absence of glucose transporter 4 diminishes electrical activity of mouse hearts during hypoxia 2013
    2013 Inducible overexpression of GLUT1 prevents mitochondrial dysfunction and attenuates structural remodeling in pressure overload but does not prevent left ventricular dysfunction 2013
    2012 Mechanisms of lipotoxicity in the cardiovascular system 2012
    2012 Genetic loss of insulin receptors worsens cardiac efficiency in diabetes 2012
    2012 Cytosolic, but not mitochondrial, oxidative stress is a likely contributor to cardiac hypertrophy resulting from cardiac specific GLUT4 deletion in mice 2012
    2011 The maximal downstroke of epicardial potentials as an index of electrical activity in mouse hearts 2011
    2011 PGC-1β deficiency accelerates the transition to heart failure in pressure overload hypertrophy 2011
    2011 Expression of slow skeletal TnI in adult mouse hearts confers metabolic protection to ischemia 2011
    2011 Knockout of insulin receptors in cardiomyocytes attenuates coronary arterial dysfunction induced by pressure overload 2011
    2010 Aberrant water homeostasis detected by stable isotope analysis 2010
    2010 Loss of bradykinin signaling does not accelerate the development of cardiac dysfunction in type 1 diabetic akita mice 2010
    2010 Preferential oxidation of triacylglyceride-derived fatty acids in heart is augmented by the nuclear receptor PPARα 2010
    2010 Lipotoxicity in the heart 2010
    2008 Insulin-like growth factor I receptor signaling is required for exercise-induced cardiac hypertrophy 2008
    2007 A role for the transcriptional coactivator PGC-1α in muscle refueling 2007
    2007 Cardiac hypertrophy caused by peroxisome proliferator-activated receptor-γ agonist treatment occurs independently of changes in myocardial insulin signaling 2007
    2007 A Conserved Role for Phosphatidylinositol 3-Kinase but Not Akt Signaling in Mitochondrial Adaptations that Accompany Physiological Cardiac Hypertrophy 2007
    2006 Diminished hepatic gluconeogenesis via defects in tricarboxylic acid cycle flux in peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)-deficient mice 2006
    2005 PGC-1α coactivates PDK4 gene expression via the orphan nuclear receptor ERRα: A mechanism for transcriptional control of muscle glucose metabolism 2005
    2005 PGC-1α deficiency causes multi-system energy metabolic derangements: Muscle dysfunction, abnormal weight control and hepatic steatosis 2005
    2004 Calcineurin and calcium/calmodulin-dependent protein kinase activate distinct metabolic gene regulatory programs in cardiac muscle 2004
    2002 Adaptations of skeletal muscle to exercise: Rapid increase in the transcriptional coactivator PGC-1 2002

    Research Overview

  • Glucose-mediated remodeling of cardiac DNA methylation - Specifically, work in the laboratory has two primary goals: 1) to determine the role of metabolic substrate switching in the hearts of individuals with diabetes or heart failure, and 2) to define the role of cellular glucose delivery on post-translational regulation of mitochondrial enzyme activity and epigenetic regulation of gene expression that together may lead to the development of diabetic cardiomyopathy. The primary goal of the R01-funded research is to determine the role glucose fluctuations in the regulation of DNA methylation in transgenic models of glucose uptake and diabetes models. Other projects in the laboratory include determining the role of the protein post-translational modification O-GlcNAc in regulating cardiac cellular function and define the role that changes in glucose levels have on long-lasting epigenetic regulation of gene expression in a process termed “glycemic memory”. Recent studies include work defining these molecular pathways in human heart failure biopsies to determine etiology specific epigenetic signatures (as published here: https://www.nature.com/articles/s41374-018-0104-x). Finally, we have initial work looking at human samples to define racial differences in epigenetic changes that in turn impact susceptibility to diabetes and heart failure. By determining these molecular signatures of altered protein regulation and DNA structure/regulation we aim to provide critical knowledge to determining future therapeutic interventions for diabetic and heart failure patients.

    Keywords - Diabetes, Hypertension, Exercise, Mitochondria, Metabolism, Glucose, Epigenetics, Gene expression, transcription, O-GlcNAc, protein modifications, DNA methylation, Histone modification, GLUT4, PDK2, PDK4
  • Full Name

  • Adam Wende