Jonathan D. Schertzer, PhD
Assistant Professor, Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences
The inability to respond to insulin is the major cause of type 2 diabetes. This insulin resistance precedes overt diabetes thereby providing therapeutic window to prevent the disease. Obesity is the main cause of insulin resistance and inflammation has emerged as a key link between obesity and insulin resistance. How does obesity cause inflammation and how does inflammation cause insulin resistance leading to diabetes? My laboratory is interested in understanding these problems inImmunoMetabolism and how dietary and bacterial factors connect immunology and metabolism.
My laboratory uses physiology in genetic mouse models coupled with cell biology and biochemistry to understand the inflammatory basis of metabolic disease. Using our ImmunoMetabolism expertise, we collaborate with immunologists, microbiologists and gastroenterologists in order to understand how the food we eat and the bacteria that colonize us can cause (or prevent) metabolic diseases. This work is particularly interested in how the bacterial cell wall component, peptidoglycan, and dietary factors such as saturated fat propagate inflammation and alter metabolism via nucleotide oligomerization domain (Nod) proteins. This research has important implications for understanding the inflammatory underpinnings of obesity and diabetes, and is complimentary to ongoing collaborative research on energy sensors and fat/glucose metabolism during obesity.
My laboratory is also very interested in the role of inflammation in muscle diseases (i.e. myopathies). This builds on a long standing interest in basic science and therapeutics targeted to muscle using both endocrine and gene therapy approaches. Given that statin drugs are the first line treatment for obesity/diabetes related cardiovascular disease, we are particularly interested in immunity and statin-induced myopathy. Working with the world-renowned neuromuscular clinic at McMaster University, we bridge basic aspects of muscle biology and clinical treatment of myopathies such as muscular dystrophy, cancer cachexia, sarcopenia (aging) and inflammatory myopthies.
- Gehrig SM, et al. HSP72 preserves muscle function and slows progression of severe muscular dystrophy. Nature, 484: 394-398, 2012
- Hawley SA, et al. The ancient drug salicylate directly activates AMP-activated protein kinase. Science, Apr 19, 2012
- Galic S, et al. Hematopoietic AMPKβ1 reduces murine adipose tissue macrophage inflammation and hepatic insulin resistance in obesity. J Clin Invest, 121: 4903-4915, 2011
- O ‘Neill HM, et al. AMPKβ1β2 muscle null mice reveal an essential role for AMPK in maintaining mitochondrial content and glucose uptake during exercise. Proc Natl Acad Sci USA, 108: 16092-7, 2011
- Schertzer JD and Klip A. Give a NOD to Insulin Resistance. Am J Physiol Endocrinol Metab 301: E585-6, 2011
- Schertzer JD, et al. NOD1 activators link innate immunity to insulin resistance. Diabetes 60: 2206-15, 2011
- Tamrakar AK, et al. NOD2 activation induces muscle cell-autonomous innate immune responses and insulin resistance. Endocrinology 151: 5624-5637, 2010
- Schertzer JD, et al. A transgenic mouse model to study GLUT4myc regulation in skeletal muscle. Endocrinology 150:1935-40, 2009
- Schertzer JD, et al. Modulation of IGF-I and IGFBP interactions enhances skeletal muscle regeneration and ameliorates the dystrophic pathology in mdx mice. Am J Pathol 171: 1180-8, 2007
- Schertzer JD and Lynch GS. Comparative evaluation of IGF-I gene transfer and IGF-I protein administration for enhancing skeletal muscle regeneration after injury. Gene Ther 13: 1657-64, 2006
- Schertzer JD, et al. Optimizing plasmid-based gene transfer for investigating skeletal muscle structure and function. Mol Ther 13: 795-803, 2006