Genetic dissection of mechanisms linking cell dysfunction, insulin resistance and major human disease

Dr Semple is an endocrinologist whose research seeks to elucidate the mechanisms underlying human insulin resistance and how insulin resistance drives pandemic diseases such as type 2 diabetes, fatty liver and subfertility. He focuses on rare, severe disorders of growth and insulin action, encompassing insulin resistance, insulin supersensitivity, dwarfism and overgrowth. He follows identification of single gene defects with targeted studies in cells, model organisms (including mice), and humans. His particular focuses at present are on activating and inhibitory mutations in the phosphatidylinositol 3-kinase/AKT signalling pathway, and on syndromes featuring severe insulin resistance due to genetic defects created during mitosis or DNA damage repair.