We use mouse genetics to understand complex problems in developmental biology, homeostasis, disease pathogenesis, and tissue regeneration.
We focus on four mains organ systems and related diseases:
- Heart and vascular response to injury.
- Lung development, response to injury and cancer
- Skeletal development, osteoporosis, degenerative joint disease.
- Inner ear development and regeneration.
Selected laboratory protocols, such as: alkaline
plasmid prep, BrdU immunohistochemistry, LacZ embryo staining, RNase
protection assay and many others.
Information and graphics concerning fibroblast growth factor research,
such as: FGF family tree, FGFR mutations, FGF specificity data and
Neurobiology and the function of Intracellular FGFs(iFGFs): Intracellular Fibroblast Growth Factors (iFGFs) are important regulators of the activity of many different neurons in the brain and throughout the body
We have identified FGF20 as an essential signal that regulates the development of sensory receptors in the inner ear. Mice lacking FGF20 are viable, healthy and congenitally deaf. FGF20 expression also marks a progenitor cell lineage in the olfactory epithelium and functions to regulate the growth of the underlying nasal turbinates. Our aims are to identify the molecular mechanisms that regulate the expression of Fgf20 during embryonic development of the cochlea and olfactory epithelium; to determine how FGF20 regulates sensory progenitor cell growth and the differentiation of cochlear outer hair and supporting cells in the organ of Corti; and to identify the specific genes and pathways that act downstream of FGF20 during cochlear and olfactory development using Next Gen mRNA sequencing (TRAP-seq). We are testing the hypothesis that FGF signaling can enhance sensory cell regeneration following ototoxic damage.
We are investigating how FGF signaling regulates osteoblast function and bone density during development and aging. We have shown that FGF signaling in the osteoprogenitor cell indirectly regulates growth plate chondrocyte proliferation and differentiation and directly regulates the metabolic activity of osteoblasts. We have also identified an autocrine FGF signal that regulates articular chondrocyte differentiation. Through these mechanisms, FGF signaling regulates longitudinal bone growth, bone mass, and homeostasis of articular cartilage.
We are investigating the function of FGF receptor signaling in specific cardiovascular lineages. We have shown that endothelial FGF receptor signaling is essential for wound healing and the hearts response to ischemia-reperfusion injury. FGF receptors are being targeted in cardiomyocytes and stromal cells of the heart and other tissues to address their role in tissue homeostasis and ischemia-reperfusion injury.
We are investigating how FGF, Wnt, and BMP signaling pathways interact to regulate growth of the lung and the complex process of branching morphogenesis. We are investigating mechanisms by which micro RNAs and other epigenetic factors regulate Fgf9 expression during development and in the pathogenesis of Pleuropulmonary Blastoma, a familial pediatric lung cancer syndrome that is initiated by mutations in DICER1. We are investigating mechanisms by which FGFs are protective in lung epithelial repair and pathogenic in pulmonary fibrosis, and we are investigating mechanisms by which FGF signaling activates adult lung progenitor cells in models of adenocarcinoma and response to injury.
Links to other programs within the School of Medicine, and to other
areas of interest.
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