Principle Investigator: Ronald Waclaw, PhD

Ronald Waclaw.RASopathies are a group of clinically distinct syndromes that are linked by gene mutations that result in a gain-of-function (GOF) of the RAS / MAPK pathway. A pathway is the way in which a cell communicates from its surface to the DNA inside of the cell. Many gene mutations in RASopathies are associated with upstream regulatory genes in the RAS pathway, but a significant subset of patients (20% to 30%) remain molecularly undiagnosed. Our team has identified patients with severe neurodevelopmental characteristics that have mutations downstream of the MAPK pathway. Specifically, we found novel mutations in the MAPK1 and ELK1 genes.

Our research will generate precision mouse models for these mutations in the MAPK1 and ELK1 genes to model a new RASopathy syndrome with neurodevelopmental characteristics. In addition, we will identify novel RAS / MAPK effector mutations that underlie RASopathy features in the nervous system. Our goal is to establish novel preclinical mouse models to better understand neurodevelopmental features and to identify targets for future treatment.