Dr. Mohammed Dehbi's Group
The overall focus of the Dr. Mohammed Dehbi's Group is to dissect the molecular mechanisms and signaling pathways leading to insulin resistance and diabetes. The group employs a combination of biochemical, cellular, and molecular tools and systems biology approaches, including genomics, transcriptomics, proteomics and metabolomics to identify genes/pathways dysregulated in diseased condition. Specimens from human subjects and cultured mammalian cells as well as knockout mouse models are used by the group. Currently, the group is focusing on three distinct research areas:
Cells cope with stressful conditions by the induction of a set of proteins called heat shock proteins (HSPs) that belong to the heat shock response system and any defect in their expression is associated with various abnormalities and pathological disorders. Obesity and diabetes are among these disorders that exhibit impaired expression of HSPs in a manner that correlates with the degree of insulin resistance. Beside their roles as chaperones, recent evidence indicate that some of the HSPs act by dephosphorylating and, thus, inactivating the JNK and IKK; 2 keys kinases that play a direct role in insulin resistance through inactivation of the substrate of insulin receptor IRS-1. We recently showed a significant reduction in the expression of DNAJB3/HSP-40 in obese and diabetic patients. We further demonstrated that DNAJB3 plays a role in glucose uptake presumably through direct interaction with JNK stress kinase. Our current focus is to evaluate its role in glucose homeostasis and insulin signaling in vivo using experimental animal model.
Role of the heat shock response in insulin resistance and diabetes:
Insulin resistance is a cardinal feature of type 2 diabetes and insulin resistant individuals are at increased risk of cardiovascular disease. Insulin resistance is manifested in skeletal muscle, liver and adipocytes and is accompanied with a compensatory increase in insulin secretion from Beta-cells. MicroRNAs (miRNAs) are small non-coding RNAs that have recently been detected in several pathological disorders. The presence of miRNAs in the extracellular environment has recently been reported in many bodily fluids including serum, saliva, urine, and placental fluid. The aim of the present study is to identify and characterize differentially expressed miRNAs in the plasma of insulin-sensitive and insulin-resistant Qatari Arab individuals. Identification of these miRNAs by deep sequencing, will allow development of biomarkers for early detection and/or better understanding of pathogenesis of insulin resistance.
Pathophysiological role of circulating microRNA in insulin resistance and diabetes:
The characterization of metabolic perturbations that precede the onset of type 2 diabetes is paramount to identify individuals at risk, especially at the early asymptomatic stages of the disease when intervention can be most effective. Given the high rate of complications associated with T2D, it is particularly important to prevent or at least delay type 2 diabetes in individuals in their early forties or before. Metabolomics is the comprehensive analysis of low-molecular weight metabolites produced by a system and has recently emerged as a powerful tool for disease diagnosis and biomarker identification. Our group uses this technology in combination with multivariate data analysis tools to try identifying T2D predictive biomarkers. We also use this technology to unravel the mechanism underlying the association between copy number variation at the salivary alpha amylase gene (AMY1) and the risk of developing diabetes and obesity.
Identification of type 2 diabetes predictive markers:
The results of these investigations should provide key insights into the pathophysiological mechanisms underlying insulin resistance and diabetes.
Dr. Mohammed Dehbi's Team
Senior Research Associate