How do components of the TGF-b signaling pathway regulate mammalian developmental processes and disease outcomes in vivo? This is the overarching question addressed in the Akhurst lab. TGF-b is required for normal embryonic development, especially vascular development and immune tolerance. It is a major player in tumor progression, including epithelial mesenchymal transformation, immunosuppression, elaboration of extracellular matrix, cancer stem cell maintenance and drug resistance, all activities that drive tumor progression and metastasis. The laboratory studies pre- and post-natal vascular development, as well as mouse models of tumorigenesis. Our studies span basic cellular molecular biology and developmental genetics, through systems genetics, to translational studies on preclinical drug development, with translational validation using human genetics, bioinformatics and analysis of human tissues.