Roger Shi Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2014

Roger Shi

Dr. Yuguang (Roger) Shi is currently a Professor at Cellular and Molecular Physiology, Penn State University College of Medicine. Dr. Shi has a longstanding research interest in translation medicine. His current laboratory at Penn State mainly focuses on molecular mechanisms underlying mitochondrial dysfunction in obesity and type 2 diabetes. His laboratory pioneered the cloning of several first in class lipid metabolic enzymes involved in cardiolipin synthesis and remodeling, including the human cardiolipin synthase-1 (hCLS1), acyl-CoA dependent lysocardiolipin acyltransferase-1 (ALCAT1), and lysophosphatidylglycerol acyltransferase-1 (LPGAT1). Cardiolipin is a mitochondrial membrane phospholipid required for oxidative phosphorylation and mitochondrial biogenesis. In contrast to other phospholipids, the biological function of cardiolipin is determined by its acyl composition, which is dominated by linoleic acid in healthy metabolic tissues, such as heart, liver, and skeletal muscle. In contrast, the onset of obesity and type 2 diabetes is associated with a significant alteration of acyl composition from the healthy tetralinoleoyl cardiolipin to the cardiolipin species enriched with docosahexaenoic acid (DHA), rendering cardiolipin highly sensitive to oxidative damage by reactive oxygen species (ROS). Oxidized cardiolipin serves as a new source of ROS, initiating a chain of events of oxidative stress and CL oxidation known as “CL peroxidation” which is implicated in the mitochondrial dysfunction in aging and age-related diseases. Dr. Shi’s lab has recently identified up-regulated ALCAT1 expression as a key mediator of mitochondrial etiology in age-related metabolic diseases. His work shows that ALCAT1 catalyzes the synthesis of cardiolipin with aberrant acyl composition linked to obesity and type 2 diabetes, leading to oxidative stress and mitochondrial dysfunction. Consequently, targeted deletion of ALCAT1 in mice ameliorates several age-related metabolic diseases, including obesity, type 2 diabetes, and diabetic complications. These findings link pathological cardiolipin remodeling by ALCAT1 to “the mitochondrial free radical aging clock” proposed by Dr. Denham Harman more than 50 years ago and refurbished by Dr. Douglas Wallace in recent years. Prior to joining Penn State, Dr. Shi was a Principle Research Scientist at Lilly Research Laboratories where spent 11 years in leading early stage R&D effort in the development of novel drugs for diabetes and obesity, including successful launch of ByettaTM©, a first in class anti-diabetes drug. His lab at Lilly was the first to identify and characterize PEK1 kinase (later known as PERK), a key regulator of ER-stress and translation control in diabetes. He authored and co-authored more than 60 papers in world class journals. He serves as a regular member of NIH study section, editorial board member of several scientific journals, and scientific consultant for a number of pharmaceutical companies.

Abstracts this author is presenting: