Shilpa Nagarajan

I was awarded a Novo Nordisk Postdoctoral Fellowship in October 2019 to work with Professor Leanne Hodson, Dr Katherine Pinnick and Professor Fredrik Karpe in OCDEM. My project explores the mechanisms that define hepatic insulin resistance in humans, particularly in the setting of lipid excess such as in non-alcoholic fatty liver disease (NAFLD). I utilise stable-isotope tracer methodologies in primary human hepatocytes and human liver cell lines to investigate the direct relationship between intracellular triglyceride pools (particularly lipid droplet morphology, composition and localisation) and hepatic glucose output. My cellular work is also complemented by stable isotope studies performed in participants of the Oxford Biobank at OCDEM to investigate pathways that underlie common markers of hepatic insulin resistance in humans (such as gluconeogenesis and de novo lipogenesis). The aims of this project are to 1) establish a physiological cell model of human hepatic insulin resistance, 2) determine what distinguishes insulin sensitive vs insulin resistant fatty livers and 3) explore plasma markers of selective hepatic insulin resistance in humans.

Before moving to Oxford for my fellowship, I completed a PhD in Medicine (Physiology) at the University of Sydney (Australia) in 2019 in Dr Andrew Hoy’s Lipid Metabolism Lab. My PhD project generated ubiquitomic, proteomic and phosphoproteomic data to investigate the role that lipid droplet proteins play in the development of insulin resistance. By investigating proteins predicted to be perturbed with obesity-induced hepatic insulin resistance, I discovered and characterised the function of a novel insulin-sensitive protein involved in the regulation of lipolysis and fatty acid oxidation in the liver.

Prior to my PhD, I obtained my Bachelor of Science (Honours) in Human Biology and Psychology from the University of Toronto (Canada), during which I began my career in diabetes research in the labs of Prof Michael Wheeler at University of Toronto and Prof Scott Summers at Duke-NUS Graduate Medical School (Singapore).