Our Research Members

My research focuses on pancreatic function and insulin sensitivity in malnutrition.

I created an animal model of malnutrition and we are studying the acute and long-term effect of malnutrition on pancreatic function and insulin action. We also have performed and are currently doing clinic studies in low resource countries.

My program of research develops and evaluates community-based prevention programming for South Asian adults and adolescents living in Canada at risk for diabetes using mixed-methods designs from a socio-ecological perspective. A current project I am leading is the South Asian Adolescent Diabetes Awareness Program (SAADAP) funded by the Child and Youth Diabetes Strategy Fund by the Lawson Foundation. I am also a present fellow at the Institute of Clinical Evaluative Sciences (ICES) examining variation in the prevalence of diabetes across immigrants from the South Asian Diaspora in Ontario.

1) Regulation of tissue uptake and metabolism/signaling properties of fatty acids, especially within the brain.2) Genetic and dietary regulation of plasma fatty acid concentrations.

My research program examines how individuals balance energy homeostasis in conditions of excess dietary fat and elevated hormones and how abnormalities in these processes can lead to obesity and chronic disease development such as Type 2 Diabetes. More specifically, my research focuses on the immense functional role of stress (glucocorticoids), gut and pancreatic hormones in adipose tissue metabolism, and other peripheral tissues. I utilize cell culture and whole animal models to tease apart the molecular and cellular regulators of energy expenditure to better understand how they govern body weight, and glucose homeostasis.

Obesity is a major global health concern and is a major risk factor for other disorders, including diabetes, hypertension, and heart disease. A complex neuronal system has evolved to maintain energy homeostasis, and also glucose homeostasis. Leptin, ghrelin, glucose, glucagon-like peptides, and insulin are known peripheral signals that act to regulate feeding and energy balance by modulating the expression of neuropeptides in the brain, specifically the hypothalamus. The afferent hormones leptin and insulin have common physiological responses and intracellular signaling mechanisms, but insulin resistance and leptin resistance are major metabolic problems, sometimes leading to type 2 diabetes. We have a strong track record of neuroendocrine research, focussing on molecular and cellular biology using hypothalamic neuronal cell models. Our research program includes studies of the regulation and signalling mechanisms in many of the neuropeptide-expressing neurons involved in energy homeostasis, and the molecular/cellular events leading to leptin/insulin resistance. Importantly, there is also a direct relationship between nutritional status and reproduction, another long-term interest of my laboratory, therefore my research program is poised to utilize all the information gained from our work to provide insight into the complex nature of integrated neuroendocrine control of basic physiology.

The main focus of research in my lab is on atherosclerosis and specifically on interactions between cells and extracellular matrix during vascular remodeling. We are investigating mechanisms of vessel wall thickening and remodeling using experimental models of arterial injury in mouse, rat and rabbit, studying the role of extracellular matrix, cell-surface integrin receptors, the novel discoidin-domain receptors and MMPs in mediating SMC responses. In collaboration with Dr. Adria Giacca, we are studying the effect of high glucose and insulin on SMC growth and matrix remodeling in atherosclerosis.

I am a transplant hepatologist and clinician-scientist using a systems biology approach to studying metabolic complications post-liver transplant. Post-transplant Diabetes Mellitus (PTDM) has been shown to significantly compromise long-term transplant patient survival in around 25% of patients. However, its pathogenesis is poorly understood with need of further investigation to implement precisely designed preventive and therapeutic strategies. My research program uses a combination of Systems Biology and Machine learning approaches to layers of data from patient samples, using in vitro and in vivo models for validation. Using this unique approach, we hope to understand and develop more precise strategies to optimize the prevention and management of PTDM in our liver transplant recipients, thereby improving their long-term survival.

My research focuses on health outcomes and quality of care related to diabetes. Specific interests include: 1) how neighbourhood characteristics (e.g. community design, the food environment) contribute to the prevalence of obesity and diabetes; 2) gender, socioeconomic, and regional differences in diabetes outcomes; 3) health care strategies to improve the quality of diabetes care and 4) the application of geographic analytic tools to health care planning. Much of this work is done using linkage of large secondary databases including provincial administrative health care data, population-based surveys and census, retail and other environmental data sources. Students and research fellows use epidemiological and health services research methods to study diabetes and its outcomes at a population-level.

Although the laboratory is now closed, the major interests of the Brubaker laboratory were related to the synthesis, secretion and biological activities of gut hormones and, in particular, the intestinal glucagon-like peptides, GLP-1 and GLP-2. These hormones play important roles in the regulation insulin and glucagon secretion, beta cell proliferation, intestinal growth and function, and food intake. GLP-1 mimetics are currently in use for the treatment of patients with Type 2 diabetes, while a long-acting GLP-2 analog has recently been approved for the treatment of patients with intestinal insufficiency due to short bowel. Some of the areas that were under investigation in the lab included:

1. Regulation of GLP-1 and GLP-2 synthesis and secretion by the intestine, with particular focus on dietary nutrients and intracellular signalling pathways; and
2. Mechanisms of action of GLP-1 and GLP-2 to stimulate beta cell and intestinal growth, respectively, with a major emphasis on the roles of novel intra- and extracellular mediators of these effects, as well as possible carcinogenic effects.

Students and fellows utilized a wide-variety of approaches to investigate the physiology and pathophysiology of the glucagon-like peptides, including normal and genetically-modified animals, cell culture and imaging approaches, in combination with tissue and cellular analyses at the mRNA and protein level.