Metabolic Regulation and Obesity
Signal Transduction/Hormone Action
Category(ies) of Research
Descriptor of Research
My long-term goal is to understand hepatic and enterocyte determinants of metabolic diseases, such as type 2 diabetes, obesity, metabolic syndrome and NAFLD. Initial post-doctoral work thus focused on the role of enterocyte GLUT9 in mammalian metabolic homeostasis. In parallel, I studied GLUT8 in enterocyte and hepatocyte fructose handling and fructose-induced metabolic syndrome. I propose in the current application to extend studies on the role of hepatocyte GLUT8 in hepatic and whole-organism energetics by evaluating the role of lysosomal GLUT8 in mTORC1 and autophagic flux regulation.
I am uniquely positioned to advance this field with training in clinical gastroenterology and intestinal physiology, glucose transporter (GLUT) cell biology (I began studying the role of GLUT1 in diabetic retinopathy pathogenesis as an undergraduate in 1998, and the role of GLUT4 and growth factor signal transduction in diabetic cardiomyopathy as a graduate student in 2003), unique reagents (e.g. backcrossed tissue-specific knockout mouse models, adenoviral and lentiviral gene constructs) and a host of sensitive, reliable assays to probe our scientific queries. Together, our work on enterocyte and hepatic GLUT8 and GLUT9 is beginning to illustrate a novel, overarching theme on which I hope to continue basic investigation – that the so-called “novel” enterocyte GLUTs are critical mediators of hepatic and global metabolic homeostasis.