The precise identification of genetic variants that predispose to human diseases is a fundamental scientific goal, paving the way to new diagnostics, treatments, and basic insights into human biology. So far these efforts focused mainly on protein-coding sequences and the identification of non-coding variants lags behind. Our research vision is to elucidate regulatory mechanisms, whereby non-coding variants influence the susceptibility to complex diseases by applying a combination of functional genomics, regulatory element analysis, human patient samples and mouse genetic engineering techniques.
Currently our efforts are focused on diseases of the connective tissue, specifically idiopathic scoliosis, and inguinal hernia. Idiopathic scoliosis is the most common musculoskeletal disorder of childhood, leading to sideways curvature of the spine and inguinal hernia is a weakening of the connective tissue leading to the protrusion of organs through the body wall. The genetic architecture of both diseases is complex, and the great majority of risk factors are undiscovered.
Our goal is to discover novel regulatory mechanisms underlying these diseases by identifying gene regulatory elements such as enhancers, which play an important role in fine-tuning gene expression and understanding how mutations in these enhancers can lead to human diseases. In addition, we will illuminate the genetic networks that the associated genes are involved in and dissect the molecular and cellular processes underlying disease pathogenesis. This disease-guided approach will shed light on global processes underlying connective tissue development and homeostasis.