Research in the laboratory of Lawrence J. Mandarino, Ph.D., focuses on the molecular mechanisms responsible for insulin resistance in skeletal muscle and liver.
Of particular interest are the roles of mitochondrial dysfunction in muscle and the regulation of structure and function of mitochondrial proteins by post-translational modifications, especially acetylation. Dr. Mandarino and his colleagues are also studying the mechanisms of fatty liver development using mouse models.
A wide variety of techniques are employed in experimental systems to study these issues, including:
- In vivo methods to assess human and mouse metabolic events, such as the euglycemic hyperinsulinemic clamp, muscle biopsies, and use of stable isotopes to assess metabolic rates
- Proteomics, cell culture and molecular biology techniques for addressing basic questions related to clinical research
- Structure/function relationships between acetylation of mitochondrial proteins and their functions
- Mechanisms of abnormal gene expression responses to exercise in the muscle of obese and type 2 diabetic patients
- Mechanisms and quantification of post-translational modifications of proteins from insulin resistant skeletal muscle and liver, using mass-spectrometry based proteomics
Significance to patient care
The goal of the laboratory is to provide detailed information about the molecular mechanisms responsible for insulin resistance in muscle and liver in people who are obese and have type 2 diabetes. This research provides new targets for treating insulin resistance, which is the basis of obesity, type 2 diabetes, cardiovascular disease, and other aspects of cardiometabolic risk—a cluster of conditions sometimes referred to as metabolic syndrome.
- Chair, Department of Kinesiology, Arizona State University, 2005-2010
- Cure Award, American Diabetes Association, 2009
- Director, Center for Metabolic and Vascular Biology, Arizona State University, 2005-present
- Associate Editor, Diabetes, 2013-present