PhD; MSc (Human Biology)
My research focuses on how genetic variants associated with Type 2 Diabetes (T2D) affect transcriptional regulation of effector genes and how pathophysiological conditions contribute to dysregulation of these T2D associated genes.
An aspect of particular interest to me is how the interplay between genetic variants and epigenetic modifications can contribute to metabolic disease. Although hundreds of genes is known to increase the risk of developing T2D, it is not always clear what their role is, and when they exert their impact. Environmental stimuli such as diets rich in glucose and fat is known to alter gene transcription and increase risk of T2D. Pharmaceutical agent’s such as exanatide used to treat T2D, also alter gene expression. However, there is a need to describe how environmental stimuli such as these can alter the transcriptional regulation of T2D associated variants, and if this can explain why some individuals are more susceptible to T2D.
The pancreatic islet is essential in regulation of whole-body metabolism, through secretion of insulin, glucagon and somatostatin. Enhancers of pancreatic islets are enriched for T2D-associated variants, highlighting that the effect of these variants are likely to impact function of pancreatic islets. I therefore work with human pancreatic islets and cultures of human-derived beta-cells and use methods such as DNA accessibility (ATAC-seq), chromatin immunoprecipitation (CHIP-seq) and chromatin configuration (Next Generation Capture-C) methods, to elucidate how T2D associated variants and environmental stimuli affect gene regulation in β-cells.