个人简介

B.Sc. (Bachelor of Science) Ph.D. (Doctor of Philosophy)

研究领域

Molecular Biology and Disease

The central focus of the Shearer laboratory is metabolic physiology. Our mission statement is to ‘Employ knowledge of metabolism to predict, prevent and treat chronic metabolic disease states’. Specific disease states of interest include obesity, cardiovascular disease and type 2 diabetes. Our genome to systems approach is unique provides the opportunity to examine both whole body and tissue specific biochemical and metabolic regulation. Specific laboratory projects are as follows: Mitochondrial Physiology. Cardiovascular disease is the primary cause of morbidity and mortality in the industrialized world. The disease often cumulates in a myocardial infarction (MI) representing tissue death resulting from prolonged or extensive ischemia. Post-MI, heart failure is a significant concern with metabolic perturbations leading to progressive cardiac remodeling. A promising therapy for these conditions includes cell-based regenerative medicine that may one day lead to treatments to recover injured myocardium. Results generated in our laboratory and others show stem cells to alter metabolism, and this to be a key mechanism by which stem cells preserve injured tissue and promote healing. Metabolic Influence of Post-translational Modifications. O-linked β-N-acetylglucosamine (O-GlcNAc) modification is an intracellular tool capable of integrating energy supply with demand. The accumulation of excess energy associated with obesity and insulin resistance is mediated, in part, by the hexosamine biosynthetic pathway (HBP) that results in the O-GlcNAcylation of a myriad of proteins, thereby affecting their respective function, stability, and localization. Insulin resistance is related to the excessive O-GlcNAcylation of key metabolic proteins causing a chronic blunting of insulin signaling pathways and precipitating the accompanying pathologies, such as heart and kidney disease. Lifestyle modifications such as diet and exercise also modify the pathway. Adenosine Receptor Antagonism. The adverse effects of acute caffeine consumption on glucose homeostasis are well-documented. Caffeine and related methylxanthines inhibit insulin-stimulated glucose uptake in the heart, isolated adipocytes and skeletal muscle preparations. In humans, reductions (-30%) in whole body glucose disposal have been shown during both oral glucose tolerance tests and euglycemic-hyperinsulinemic clamps. Work in this area examines the metabolic impacts of caffeine-containing energy drinks on insulin resistance in lean and obese adolescents.

近期论文

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Watts, R., Johnsen, V.L., Hughey, C.C., Shearer, J. Hittel, D.S. Myostatin inhibits hepatocyte proliferation by down-regulating the long noncoding RNA Malat1. Biochemistry and Cell Biology, bcb-2014-0004.R1. Feb 2014. In Press Myslicki, J. P., Hittel, D.S., Hughey, C.C., Belke, D.D., Shearer, J. Role of O-GlcNAcylation in Nutritional Sensing, Insulin Resistance and in Mediating the Benefits of Lifestyle Modification. Applied Physiology Nutrition & Metabolism APNM-2014-0122. In Press. April 2014. Connors, K.E., Karols, A.E., Gnatiuk, E.A., Shearer, J., Hittel, D.S. SORT1 Minor, Protective Allele is Associated with Attenuated Postprandial Lipaemia in Young Adults. Circulation, Cardiovascular Genetics, CIRCCVG/2014/000534. In Press Shearer, J. Caffeinated energy drinks: methodological considerations and impact on the gastrointestinal system, liver and metabolic health. National Institutes of Health: The Use and Biology of Energy Drinks, Current Knowledge and Critical Gaps Meeting, August 2013. Invited Review. Nutrition Reviews. Nov 2013. NUTR-REV-039-SUPPL-02-2014. In Press. Shearer, J., Graham, T.E. Caffeine and Caffeinated Energy Drink Consumption: A Systematic Review of Performance and Metabolic Consequences on Glucose Disposal. National Institutes of Health: The Use and Biology of Energy Drinks, Current Knowledge and Critical Gaps Meeting. Invited Review. Nutrition Reviews. Nov 2013. NUTR-REV-038-SUPPL-02-2014. In Press. Cowan, T.E., Palmnas, M.S.A., Yang, J., Bomhof, M.R., Ardell, K., Reimer, R.A., Vogel, H.J., Shearer, J. Chronic coffee consumption in the diet-induced obese rat: impact on gut microbiota and serum metabolomics. Journal of Nutritional Biochemistry, JNB-13-670.R1. 2014 (Journal Ranked 8/76 in Nutrition and Dietetics 2012, Journal Citation Reports). PMID: 24629912 Hasenour, C.M., Hughey, C.C., James, F.D., Viollet, B., Foretz, M., Donahue, E.P., Shearer, J., Wasserman, D.H. AMPK mediates 5-Amnioimidazole-4-carboxamide-1-D-ribofuraniside (AICAR) effects on energy metabolism but not glucose production in vivo. Journal of Biological Chemistry, Feb 28;289(9):5950-9, 2014. PMID: 24403081. Hughey, C.C., Johnsen, V., Ma, L., James, F.D., Young, P.P., Wasserman, D.H., Rottman, J.N., Hittel, D.S., Shearer, J. Mesenchymal Stem Cell Transplantation for the Infarcted Heart: Therapeutic potential beyond the heart in the presence of diet-induced insulin resistance. Cardiovascular Diabetology, 4:12(2):128. 2013. PMID: 24007410 Hughey, C.C., Johnsen, V., Ma, L., James, F.D., Young, P.P., Wasserman, D.H., Rottman, J.N., Hittel, D.S., Shearer, J. Mesenchymal stem cell transplantation for the infarcted heart: reducing impairments in insulin-stimulated glucose uptake in vivo. American Journal of Physiology – Cell Physiology, May 15;304(10):C995-1001, 2013. PMID: 24196528 Nyamandi, V.Z., Johnsen, V.L., Hughey, C.C., Hittel, D.S., Khan, A., Shearer, J. Intravenous mesenchymal stem cell administration modulates hepatic reactive oxygen species production in diet-induced obesity. Obesity Jul 26. doi: 10.1002/oby.20580, 2013. PMID: 23894091 Eller, L.K., Saha, D.C., Shearer, J., Reimer, R.A. Dietary leucine improves whole body insulin sensitivity independent of body fat in diet-induced obese Sprague-Dawley rats. Journal of Nutritional Biochemistry. S0955-2863(12)00273-2, 2013. PMID: 23332601. Watts, R., Johnsen, V.L. Shearer, J., Hittel, D.S. The myostatin-induced inhibition of the long noncoding RNA Malat1 is associated with decreased myogenesis. American Journal of Physiology, Cell Physiology. 304(10):C995-1001, 2013. PMID: 23485710 Johnsen, V.L., Belke, D.D., Hughey, C.C., Hittel, D.S., Hepple, R.T., Koch, L.G., Britton, S.L., Shearer, J. Enhanced cardiac protein glycosylation (O-GlcNAc) of selected mitochondrial proteins in rats artificially selected for low running capacity. Physiological Genomics. 45(1): 17-25, 2013. PMID: 2313275 Bennett, C.E., Johnsen, V.L., Shearer, J., Belke, D.D. Exercise training mitigates aberrant cardiac protein O-GlcNAcylation in streptozotocin-induced diabetic mice. Life Sciences. 92(11):657-63, 2013. PMID: 23132757. Karlos, A., Shearer, J., Gnatiuk, E., Chiatogu, O., Many, G., Hoffman, E., Hittel, D.S. The effect of the SORT1 LDL-cholesterol locus is sex specific in a fit, Canadian young adult population. Applied Physiology Nutrition & Metabolism. 38(2): 188-93, 2013. PMID: 23438231