Using human skeletal dysplasias and corresponding mouse models, Dr. Lee has focused on identifying novel genetic mechanisms that regulate skeletogenesis. As a graduate student, he identified the first genetic defects for human chondrodysplasias. As a postdoctoral fellow, he identified the gene for Marfan syndrome. As an independent faculty, he identified the consequences of human mutations in two critical transcription factors Runx2 and Lmx1b important in osteoblast differentiation and limb patterning, respectively. Most recently, he has identified the pathogenetic role of a dysregulated collagen post-translational modification in osteogenesis imperfecta. Finally, his study of human skeletal dysplasias has led him to identify critical components of the transcriptional hierarchy that regulates mesenchymal stem cell differentiation to the osteoblastic versus chondrogenic lineages.