Overview
I am a Professor of Medicine the Director of the Molecular and Cellular Analysis (MCA) core of our Nutrition and Obesity Research Center (NORC). I have served in this capacity for the NORC for over 5 years, overseeing services related to lipidomics, isotopic enrichment analysis, a genomic/transcriptomic sample pipeline, and measurements of mitochondrial and cellular respiration. My research program focuses on the relationship between fat stored inside of muscle, and adipose tissue adjacent to muscle on insulin sensitivity in humans. I have training in exercise physiology as well as physiology of obesity and insulin resistance, with specific experience in areas essential to the success of the proposed project. For example, I have been recruiting and testing human subjects for research projects for the past 25 years, including subjects with obesity, pre-diabetes, and diabetes for the past 20 years. I have been studying the influence of intramuscular triglyceride and related bioactive lipid intermediates with continuous NIH funding for the past 15 years. As PI or co-investigator on several NIH-funded grants, I have shown my team’s ability to recruit obese and insulin resistant people for research studies, perform hyperinsulinemic-euglycemic clamps, and measure multiple lipid species using LC/MS instrumentation from muscle biopsies. Personnel in my laboratory are currently focused on how intramuscular lipids, specifically diacylglycerol and ceramide, influence insulin sensitivity in humans. We have published the first study in humans showing that diacylglycerol species are compartmentalized in skeletal muscle, which influences activation of protein kinase C and insulin resistance, and that C18:0 ceramide is uniquely related to muscle insulin resistance in humans. We published a study in JCI Insight showing the complexity of localized muscle lipids and species in human skeletal muscle from individuals spanning the range of insulin sensitivity. My laboratory is also funded by NIH to elucidate how intermuscular adipose tissue promotes insulin resistance and sarcopenia in humans. Intermuscular adipose tissue is marbled in skeletal muscle and is negatively related to the risk of developing diabetes and cardiovascular disease. This project is the first study to directly sample this unique adipose tissue in humans to compare the secretome to subcutaneous and visceral adipose tissue, and evaluate mechanisms by which local paracrine signaling impacts neighboring skeletal muscle insulin sensitivity, size, and strength. The overall goal of my research is to uncover novel therapeutic targets to increase muscle insulin sensitivity, a need not met by currently therapies, to help prevent and treat type 2 diabetes.
