I became a scientist after learning that my wife, Sonia Vallabh, inherited a lethal genetic mutation in the PRNP gene from her late mother. Her mother had died of genetic prion disease, a rapidly progressive dementia caused by misfolding of the prion protein (PrP). Today, Sonia and I co-run a lab based at the Broad Institute, where our singular goal is to make prion disease a treatable and preventable condition in our lifetime. We work with multiple species of animal models as well as cell culture and in vitro systems, and we also utilize human cerebrospinal fluid and blood samples from a clinical cohort study at Massachusetts General Hospital. Our work has four main pillars. First, we undertake therapeutic development: working to validate therapeutic hypotheses, discover drug compounds, and understand mechanisms of action through biophysical and biochemical approaches and animal models. Second, we develop and characterize biomarkers, using both animal and human samples, with the goal of being able to detect drug activity, measure disease process, and enable clinical trials. Third, we use human genomic data to gain in vivo, whole organism insights about the biology of the organism we care most about. Fourth, we seek to understand disease mechanism by building systems, models, and assays to help elucidate how disease works on a molecular level, and inspire the next generation of therapies. Our laboratory is oriented around our translational mission. Success for us will mean transforming the treatment of prion disease for both newly diagnosed patients and people living at genetic risk.