The Johnson Laboratory uses mouse models to study human development and disease. We have generated and analyzed over twenty five transgenic and/or knock-out strains covering a broad range of phenotypes and systems, including the developing limb, axial skeleton, heart, eye and liver. Highlights include the identification of mutations in LMX1B that cause nail patella syndrome and analysis of Lmx1b mutant mice that have limb, kidney and eye defects, generation and analysis of lunatic fringe mutant mice that model syndromic human vertebral defects. More recently, we have focused on Hippo signaling, an emerging growth and tumor suppressor pathway central to cancer progression and resistance in many human malignancies. Through analysis of mice with tissue-specific mutations in key Hippo pathway components we have shown that Hippo signaling is an essential regulator of liver development, homeostasis, regeneration, and is a potent tumor suppressor pathway in the mammalian liver. In collaboration with researchers at MD Anderson Cancer Center and elsewhere we have also studied the role of Hippo signaling in multiple organ systems, including the kidney, pancreas, brain, eye and immune system. Currently the laboratory is focused on targeting the Hippo signaling pathway to prevent and treat advanced liver malignancies.