The incidence of obesity and a cluster of disorders associated with obesity such as type 2 diabetes, hepatosteatosis, dyslipidemia and cardiovascular disease have risen to alarming proportions and there is great need for effective therapeutic and preventive measures against these health threats. Metabolic disorders often affect an intertwined network of signaling and metabolic pathways and it is crucial to understand the interactions of these pathways in a patient-specific setting for drug target discovery and therapy development. Using transcription activator-like effector nucleases (TALENs) and CRISPR technologies, we are producing iPS cells carrying known mutations in the genes that are associated with diabetes or hepatosteatosis demonstrated by genome-wide association studies. We are differentiating these iPS cells into metabolic cells such as myotubes, hepatocytes or adipocytes and investigating potential defects in metabolic pathways that might cause the pathological conditions associated with these mutations.
