The overall focus of my laboratory is on in vivo functions of Fibroblast Growth Factors (FGFs), their interactions with other signaling pathways, and their role in tissue regeneration, response to injury, and cancer. We use in vivo mouse models to study mechanisms of organogenesis and apply our knowledge of developmental processes to understand mechanisms regulating tissue homeostasis, and reactivation of developmental programs in oncogenesis and in tissue regeneration in response to injury.
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.
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 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. We are testing the hypothesis that FGF signaling can enhance sensory cell regeneration following ototoxic damage.
Back row: Yutao Su, Andrew Hagan, David Ornitz, Craig Smith
Front row: Ling Li, Yongjun Yin, Kel Vin Woo, Traian Lupu, Stephen Stone
University of CA, Davis B.S. 1981 Biochemistry
University of WA, Seattle Ph.D. 1987 Biochemistry
University of WA, Seattle M.D. 1988 Medicine
Harvard Medical School Post doc 1988-92 Genetics
Scholarships and Awards
Washington University, Distinguished Investigator Award
Washington University, Outstanding Faculty Mentor Award
American Heart Association Established Investigator Award
Arnold and Mabel Beckman Young Investigators Award
Lucille Markey Award
Medical Scientist Training Program
American Heart Association Student Research Associates Program
1/08-present Alumni endowed Professor of Developmental Biology
1/08 – 12/09 Interim Head, Department of Developmental Biology
10/04-12/07 Interim Head, Department of Molecular Biology and Pharmacology
4/02-12/07 Alumni Endowed Professor of Molecular Biology and Pharmacology
7/00-4/02 Professor, Department of Molecular Biology and Pharmacology, Washington University Medical School
11/96-6/00 Associate Professor, Department of Molecular Biology and Pharmacology, Washington University School of Medicine
5/92-10/96 Assistant Professor, Department of Molecular Biology and Pharmacology, Washington University School of Medicine
7/88-4/92 Postdoctoral Fellow with Dr. Philip Leder, Department of Genetics, Harvard Medical School
- Oladipupo, S. S., Smith, C., Santeford, A., Park, C., Sene, A., Wiley, L. A., Osei-Owusu, P., Hsu, J., Zapata, N., Liu, F., et al. (2014). Endothelial cell FGF signaling is required for injury response but not for vascular homeostasis. Proc Natl Acad Sci U S A 111, 13379-13384.
- Guzy, R. D., Stoilov, I., Elton, T. J., Mecham, R. P. and Ornitz, D. M. (2015). Fibroblast growth factor 2 is required for epithelial recovery, but not for pulmonary fibrosis, in response to bleomycin. Am. J. Respir. Cell Mol. Biol. 52, 116-128.
- House, S. L., Wang, J., Castro, A. M., Weinheimer, C., Kovacs, A. and Ornitz, D. M. (2015). Fibroblast growth factor 2 is an essential cardioprotective factor in a closed-chest model of cardiac ischemia-reperfusion injury. Physiological reports 3, e12278-e12278.
- Huh, S. H., Warchol, M. E. and Ornitz, D. M. (2015). Cochlear progenitor number is controlled through mesenchymal FGF receptor signaling. Elife 4, 1-17.
- Yin, Y., Castro, A. M., Hoekstra, M., Yan, T. J., Kanakamedala, A. C., Dehner, L. P., Hill, D. A. and Ornitz, D. M. (2015). Fibroblast Growth Factor 9 Regulation by MicroRNAs Controls Lung Development and Links DICER1 Loss to the Pathogenesis of Pleuropulmonary Blastoma. PLoS Genet 11, e1005242.
- Yu, K., Karuppaiah, K. and Ornitz, D. M. (2015). Mesenchymal fibroblast growth factor receptor signaling regulates palatal shelf elevation during secondary palate formation. Dev Dyn 244, 1427-1438.
- House, S. L., Castro, A. M., Lupu, T. S., Weinheimer, C., Smith, C., Kovacs, A. and Ornitz, D. M. (2016). Endothelial fibroblast growth factor receptor signaling is required for vascular remodeling following cardiac ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 310, H559-571.
- Hung, I. H., Schoenwolf, G. C., Lewandoski, M. and Ornitz, D. M. (2016). A combined series of Fgf9 and Fgf18 mutant alleles identifies unique and redundant roles in skeletal development. Dev Biol 411, 72-84.
- Karuppaiah, K., Yu, K., Lim, J., Chen, J., Smith, C., Long, F. and Ornitz, D. M. (2016). FGF signaling in the osteoprogenitor lineage non-autonomously regulates postnatal chondrocyte proliferation and skeletal growth. Development 143, 1811-1822.
- Yin, Y., Ren, X., Smith, C., Guo, Q., Malabunga, M., Guernah, I., Zhang, Y., Shen, J., Sun, H., Chehab, N., et al. (2016). Inhibition of fibroblast growth factor receptor 3-dependent lung adenocarcinoma with a human monoclonal antibody. Dis Model Mech 9, 563-571.