Research Abstract
Work in the Warman lab focuses on understanding biologic pathways that affect the patterning, growth, and maintenance of the skeletal system. Our long-term goal is to improve human skeletal health. We initially identified biologic pathways through the study of patients and their families who have well-defined heritable disorders affecting bones and joints; using this approach we determined that the Wnt signaling pathway is a key regulator of bone mass acquisition, the natriuretic peptide signaling pathway is an important effector of postnatal linear growth, and the glycoprotein lubricin is the principal boundary lubricant in articulating joints. We are currently employing biochemical, cellular, and model organism approaches to precisely delineate the roles of these pathways and proteins during growth and homeostasis. We have also extended our patient-oriented research to include families with unique syndromes and patients with sporadically occurring skeletal diseases. This has enabled us to identify a missense mutation in the nuclear pore protein, RANBP2, as a susceptibility locus for a novel, environmentally triggered, neurodegenerative disease, and several de novo microduplications or microdeletions as causes of sporadically occurring malformations that affect the patterning of the limbs and spine. These latter studies serve as an entrée toward our ultimate goal of being able to provide truly “personalized†genetic medicine to every patient with skeletal disease in whom a genetic contribution is suspected.
