Carsten Schmitz-Peiffer undertook his PhD with Professor Dick Denton at Bristol University (UK), where he investigated insulin signal transduction and the regulation of fat cell metabolism. He then joined the Garvan Institute to investigate mechanisms by which lipid oversupply could interfere with normal insulin action. His research showed an association between protein kinase C activation and lipid-induced insulin resistance in skeletal muscle. Subsequently he demonstrated a causative link between intracellular accumulation of the lipid intermediate ceramide and the inhibition of insulin action caused by the saturated fatty acid palmitate. It is thus clear that different fatty acids act through different mechanisms to reduce insulin sensitivity.
In addition, the study of mice deficient in specific protein kinase C isoforms has indicated that these enzymes play multiple and unexpected roles in the control of glucose and lipid metabolism, beyond the mere inhibition of proximal insulin signalling as currently widely assumed, and the understanding of the diverse mechanisms involved is a major focus of his work. His research group employs animal models of insulin resistance in combination with transgenic mice, as well as proteomic and lipidomic approaches at both the in vivo and in vitro level, to generate new insights into the molecular mechanisms involved in the defective insulin action seen in obesity and Type 2 diabetes.
Carsten Schmitz-Peiffer has been a member of the program organising committee for the Australian Diabetes Society annual scientific meeting (2009-2011), as well as a member of NHMRC Endocrinology and Biochemistry grant review panels (2006, 2011-2012). Within the Garvan, he has chaired the Faculty (2010), the Common Users of Building and Equipment (CUBE) Committee (1996-2010) and the Seminar Committee (2007-2012), and currently chairs the Facilities and Equipment Committee.
Awards and Honours
2007 Garvan Institute High Impact Publication Prize
2006 - Senior Research Fellowship, Garvan Institute
1987 - Smith Kline & French/Bristol University CASE Award, UK
1986 - Exibitioner, Natural Sciences, Cambridge University, UK
1987 - BA (Hons) Natural Sciences, Cambridge University - UK
Methods for identifying modulators of protein kinase C-epsilon (PKCε) and method of treatment of aberrant glucose metabolism associated therewith
Brandon AE, Liao BM, Diakanastasis B, Parker BL, Raddatz K, McManus SA, O'Reilly L, Kimber E, van der Kraan AG, Hancock D, Henstridge DC, Meikle PJ, Cooney GJ, James DE, Reibe S, Febbraio MA, Biden TJ, Schmitz-Peiffer C. Protein Kinase C Epsilon Deletion in Adipose Tissue, but Not in Liver, Improves Glucose Tolerance. Cell Metab (2018) In Press
Turner N, Lim XY, Toop HD, Osborne B, Brandon AE, Taylor EN, Fiveash CE, Govindaraju H, Teo JD, McEwen HP, Couttas TA, Butler SM, Das A, Kowalski GM, Bruce CR, Hoehn KL, Fath T, Schmitz-Peiffer C, Cooney GJ, Montgomery MK, Morris JC, Don AS. A selective inhibitor of ceramide synthase 1 reveals a novel role in fat metabolism. Nat Commun (2018) 9:3165
Chandrashekaran IR, Norton RS, Schmitz-Peiffer C. Characterisation of peptide interactions that regulate PKCepsilon activation. FEBS Lett (2018) 592:179-189
B. M. Liao, S. A. McManus, W. E. Hughes, C. Schmitz-Peiffer. Flavin-Containing Monooxygenase 3 Reduces Endoplasmic Reticulum Stress in Lipid-Treated Hepatocytes. (2016) Mol Endocrinol. 30(4):417-28.
Liao BM, Raddatz K, Zhong L, Parker BL, Raftery MJ, Schmitz-Peiffer C. Proteomic Analysis of Livers from Fat-fed Mice Deficient in Either PKC delta or PKC epsilon Identifies Htatip2 as a Regulator of Lipid Metabolism. (2014) Proteomics 14:2578-87
Frangioudakis G, Diakanastasis B, Liao M, Saville J, Mitchell T, Schmitz-Peiffer C. Ceramide accumulation in L6 skeletal muscle cells due to increased activity of ceramide synthase isoforms has opposing effects on insulin action to that caused by palmitate treatment. (2013) Diabetologia 56:2697-701
Schmitz-Peiffer C. The tail wagging the dog - regulation of lipid metabolism by protein kinase C. (2013) FEBS J 280:5371-83
Pedersen DJ, Diakanastasis B, Stockli J, Schmitz-Peiffer C. Protein kinase C ε modulates insulin receptor localization and trafficking in mouse embryonic fibroblasts. PLoS ONE (2013) 8:e58046
Raddatz K, Frangioudakis G, Diakanastasis B, Liao BM, Leitges M, Schmitz-Peiffer C. Deletion of protein kinase Cε in mice has limited effects on liver metabolite levels but alters fasting ketogenesis and gluconeogenesis. (2012) Diabetologia 55:2789-93
Raddatz K, Turner N, Fangioudakis G, Liao M, Cantley J, Wilks D, Preston E, Hegarty BD, Leitges M, Raftery M, Biden TJ and Schmitz-Peiffer C. Time-dependent effects of PKCε deletion on glucose homeostasis and hepatic lipid metabolism in short term and chronic models of dietary lipid oversupply. (2011) Diabetologia 54:1447-1456
Schmitz-Peiffer C. Invited Commentary: Targeting de novo ceramide synthesis to improve insulin resistance. (2010) Diabetes 59: 2351-2353
Frangioudakis G, Garrard J, Raddatz K, Nadler JL, Mitchell TW, Schmitz-Peiffer C. Saturated and n-6 polyunsaturated fat diets each induce ceramide accumulation in mouse skeletal muscle: reversal and improvement of glucose tolerance by lipid metabolism inhibitors. (2010) Endocrinology 151:4187-96
Frangioudakis G, Burchfield JG, Narasimhan S, Cooney GJ, Leitges M, Biden TJ, Schmitz-Peiffer C. Diverse roles for protein kinase C delta and protein kinase C epsilon in the generation of high-fat-diet-induced glucose intolerance in mice: regulation of lipogenesis by protein kinase C delta. (2009) Diabetologia 52:2616-2620
Schmitz-Peiffer C, Biden TJ. (2008) Perspectives in Diabetes: Protein kinase C function in muscle, liver, and beta-cells and its therapeutic implications for type 2 diabetes. Diabetes 57: 1774-1783
Schmitz-Peiffer C, Laybutt DR, Burchfield JG, Gurisik E, Narasimhan S, Mitchell CJ, Pedersen DJ, Braun U, Cooney GJ, Leitges M, Biden TJ. (2007) Inhibition of PKC epsilon Improves Glucose-Stimulated Insulin Secretion and Reduces Insulin Clearance. Cell Metab. 6:320-328