Conjoint Associate Professor
Associate Professor Carsten Schmitz-Peiffer
BA (Natural Sciences) Cambridge, UK
PhD (Biochemistry) Bristol, UK
Medicine & Health
School of Clinical Medicine
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.
Phone
02 9295 8212
Location
Garvan Institute
384 Victoria Street
DARLINGHURST NSW 2010
- Publications
- Grants
- Awards
- Research Activities
- Engagement
- Teaching and Supervision
Carsten Schmitz-Peiffer has obtained over $3 million in peer-reviewed grant funding as CIA. He has been awarded 6 NHMRC project grants as CIA since 2003, and an NHMRC Development Grant as CIB (2007). He has also received funding from Diabetes Australia Research Trust (9 grants since 2002), Eli Lilly Endocrinology Research Grants (2 grants) and a Perpetual Impact Grant (2019-2023) as CIA.
NHMRC
2015-2019 NHMRC Project Grant $872,512
Action of PKC epsilon in Adipose Tissue Regulates Hepatic Glucose Production
CIA: C. Schmitz-Peiffer, CIB: T.J. Biden
2011-2013 NHMRC Project Grant $583,390
Targeting ceramide metabolism to improve insulin resistance
CIA: C. Schmitz-Peiffer, CIB: T. Mitchell
2009-2011 Project Grant $622,500
The regulation of insulin action in liver and skeletal muscle by Protein kinase C epsilon
CIA: C. Schmitz-Peiffer, CIB: T.J. Biden
2008-2010 Project Grant $483,750
Dilinoleoyl phosphatidic acid as a novel mediator of insulin resistance in muscle.
CIA: C. Schmitz-Peiffer, CIB: T. Mitchell
2006-2008 Project Grant $614,625
Investigation of the roles of Protein Kinase Cε in insulin secretion and insulin clearance.
CIA: C. Schmitz-Peiffer, CIB: T.J. Biden
2007 Development Grant $154,500
Therapeutic Strategies and Screening Methods for PKC epsilon antagonists in the treatment of Type 2 diabetes
CIA: T.J. Biden, CIB: C. Schmitz-Peiffer
2003-2005 New Investigator Grant $450,000
The Role of Protein Kinase Cε in the Generation of Lipid-Induced Insulin Resistance in Skeletal Muscle
CIA: C. Schmitz-Peiffer
Other Grants
2019-2023 Perpetual Impact Grant $260,000
Identifying new dual action therapies for the treatment of type 2 diabetes
Chief Investigator: C. Schmitz-Peiffer
2019 Diabetes Australia Research Trust $60,000
Using Biosensors To Determine the Role of PKCε in Adipose Tissue
Chief Investigator: C. Schmitz-Peiffer
2018 Diabetes Australia Research Trust $60,000
Dual Deletion of PKCepsilon and CerS6 in Adipose Tissue to Protect Insulin Sensitivity
Chief Investigator: C. Schmitz-Peiffer
2016 Diabetes Australia Research Trust $60,000
Inhibitors of Protein Kinase C Epsilon (PKCe) for the Treatment of Type 2 Diabetes
Chief Investigators: R. Norton, C. Schmitz-Peiffer
2015 Diabetes Australia Research Trust $60,000
The role of protein kinase C in the regulation of lipid metabolism and glucose homeostasis
Chief Investigator: C. Schmitz-Peiffer
2012 Diabetes Australia Research Trust $39,000
The role of branched chain amino acid degradation in the improvement of glucose homeostasis caused by protein kinase C epsilon deletion
Chief Investigator: C. Schmitz-Peiffer
2011 Diabetes Australia Research Trust $60,000
Regulation of Insulin Receptor Function by PKC epsilon
Chief Investigator: C. Schmitz-Peiffe
2008 Eli Lilly Endocrinology Research Grant, $40,000
Project: Inhibition of lysophosphatidic acid acyl transferase (LPAAT) as a treatment for insulin resistance and Type 2 diabetes
Chief Investigator: C. Schmitz-Peiffer
2007 Rebecca L. Cooper Medical Research Foundation
Equipment Grant: $20,000
Chief Investigator: C. Schmitz-Peiffer
2006 Diabetes Australia Research Trust, $30,000
Project: Investigation of the role of Protein Kinase Cε in insulin clearance.
Chief Investigator: C. Schmitz-Peiffer
2005 Eli Lilly Endocrinology Research Grant, $30,000
Project: The Role Of The Protein Kinase mTOR In Lipid-Induced Insulin Resistance In Skeletal Muscle Cells
Chief Investigator: C. Schmitz-Peiffer
2004 Diabetes Australia Research Trust, $40,000
Project: Inhibitory Regulation of Glycogen Synthase by Unsaturated Fatty Acid
Chief Investigator: C. Schmitz-Peiffer
2002 Diabetes Australia Research Trust, $40,000
Project: Unsaturated Fatty Acid, PKC And n-3 Fatty Acid Effects On Insulin Signalling.
Chief Investigator: C. Schmitz-Peiffer
Support for Translational Projects
2015 European Lead Factory Public Target Programme ELFSC13_04
Inhibitors Of the interaction of PKCe and RACK2 As Agents For The Treatment Of T2D
ELF to perform HTS AlphaScreen for inhibitors of PKCε-RACK2 interaction, confirm hits, deselect non-specific hits, dose response curve, selectivity profile, orthogonal assays.
Chief Investigators: Dr Graeme Wilkinson (The Research Network, UK); C. Schmitz-Peiffer
2014 AstraZeneca / Academic Drug Discovery Consortium
Free access to ready-to-screen 250,000 compound library worth $130,000
Inhibitors of protein kinase C epsilon as agents for the treatment of type 2 diabetes
Chief Investigators: C. Schmitz-Peiffer, J. Baell, K. Laclovic, T.J. Biden
2012 Regeneus Pty Ltd, $30,000
Mesenchymal stem cells as a therapy for Type 2 diabetes
Chief Investigator: C. Schmitz-Peiffer
2010 Garvan Institute Business Development funding $97,000
Use of peptide inhibitors of PKCε to treat glucose intolerance
Chief Investigators: T.J. Biden, C. Schmitz-Peiffer
2006 Devgen NV, $20,000
Treatment of pancreatic β-cell dysfunction and insulin resistance by inhibition of PKCε
Chief Investigators: C. Schmitz-Peiffer, T.J. Biden
Garvan Institute High Impact Publication Prize 2019
Garvan Institute High Impact Publication Prize 2007
Investigating the relationship between insulin resistance and lipid metabolism
A major factor in the development of type 2 diabetes is the insulin resistance of tissues such as liver and skeletal muscle. Although the mechanisms involved are not fully understood, there is a close association between insulin resistance and increased lipid availability. Our lab has previously identified the roles played by protein kinase C (PKC) and specific inhibitory lipid intermediates, especially the sphingolipid ceramide.
We employ in vivo models and knockout mice, as well as cell culture systems and proteomic and lipidomic technologies, to investigate novel pathways and identify new strategies for type 2 diabetes therapies. We also pursue the translation of our findings into clinical settings, using novel or existing drugs that target PKCs and inhibitory lipids to improve glucose homeostasis.
Our research goals are:
- To define the interactions between PKC, lipid metabolism and insulin action.
Our research has shown that the currently-held view that PKCs act solely to suppress proximal insulin signal transduction is an oversimplification. We will extend our novel findings, which show that these kinases and their specific downstream mediators play key roles in the control of lipid storage and oxidation in liver, and other insulin target tissues. This work will have relevance not only to diabetes but also hepatic steatosis, cardiovascular disease and the metabolic syndrome.
- To examine the effectiveness of targeting key molecules for the treatment of diabetes, using new and existing drugs.
We will further pursue the translation of our basic research findings into clinical settings. We will test existing inhibitors of PKC isoforms in vivo and in vitro, to determine their effectiveness in improving insulin action. Because of specificity problems with targeting kinase catalytic activity, we have also initiated a project to generate novel PKC inhibitors using other strategies.