The overall focus of the Ornitz laboratory is on the in vivo functions of Fibroblast Growth Factors (FGFs), their interactions with other signaling pathways, and their role in development, tissue homeostasis, regeneration, and injury response. We use in vivo mouse models to study mechanisms of organogenesis and we apply our knowledge of developmental mechanisms to understand how growth factors regulate tissue homeostasis, and how reactivation of developmental programs function in tissue regeneration and injury response.
We are investigating how FGF signaling in the osteoblast lineage regulates bone density during postnatal bone growth and aging. We are studying an FGF regulated signaling center adjacent to the growth plate that controls longitudinal bone growth. We are investigating mechanisms by which FGF signaling in osteoblasts regulates bone homeostasis, osteoblast anabolic activity, and osteocyte survival.
We are investigating how FGF signaling pathways regulate mesenchymal cells within the secondary septae during postnatal alveologenesis. These studies are aimed towards improving the outcomes of premature birth and preventing or treating bronchopulmonary dysplasia. We are investigating mechanisms by which FGFs are protective in lung epithelial repair and hypoxia-induced pulmonary hypertension, and we are investigating mechanisms by which FGF signaling activates adult lung progenitor cells in models of epithelial injury.
We are developing a mouse model for heart failure with preserved ejection fraction (HFpEF) and investigating the function of FGF receptor signaling in fibroblasts, myofibroblasts, and vascular smooth muscle in the heart. FGF receptors are being targeted in cardiomyocytes and stromal cells of the heart and other tissues to address their role in disease pathogenesis and injury response.
Fibroblast Growth Factor signaling in cardiovascular, lung, and skeletal development, homeostasis, injury response, and regeneration.
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
- Wernle KK, Sonnenfelt MA, Leek CC, Ganji E, Sullivan AL, Offutt C, Shuff J, Ornitz DM, Killian ML. Loss of Fgfr1 and Fgfr2 in Scleraxis-lineage cells leads to enlarged bone eminences and attachment cell death. Dev Dyn. 2023 PubMed PMID: 37212424. https://www.ncbi.nlm.nih.gov/pubmed/37212424
- Matsiukevich D, Kovacs A, Li T, Kokkonen-Simon K, Matkovich SJ, Oladipupo SS, Ornitz DM. Characterization of a robust mouse model of heart failure with preserved ejection fraction. Am J Physiol Heart Circ Physiol. 2023;325(2):H203-H31 PubMed PMID: 37204871. https://www.ncbi.nlm.nih.gov/pubmed/37204871
- Matsiukevich D, House SL, Weinheimer C, Kovacs A, Ornitz DM. Fibroblast growth factor receptor signaling in cardiomyocytes is protective in the acute phase following ischemia-reperfusion injury. Front Cardiovasc Med. 2022;9:1011167 PubMed PMID: 36211556; PMCID: PMC9539275. https://www.ncbi.nlm.nih.gov/pubmed/36211556
- Woo KV, Shen IY, Weinheimer CJ, Kovacs A, Nigro J, Lin CY, Chakinala M, Byers DE, Ornitz DM. Endothelial FGF signaling is protective in hypoxia-induced pulmonary hypertension. J Clin Invest. 2021;131(17) PubMed PMID: 34623323; PMCID: PMC8409583. https://www.ncbi.nlm.nih.gov/pubmed/34623323
- Yin Y, Ornitz DM. FGF9 and FGF10 activate distinct signaling pathways to direct lung epithelial specification and branching. Sci Signal. 2020;13(621):eaay4353 PubMed PMID: 32127497; PMCID: PMC7271816. https://www.ncbi.nlm.nih.gov/pubmed/32127497
- Stone SI, Wegner DJ, Wambach JA, Cole FS, Urano F, Ornitz DM. Digenic Variants in the FGF21 Signaling Pathway Associated with Severe Insulin Resistance and Pseudoacromegaly. J Endocr Soc. 2020;4(12):bvaa138 PubMed PMID: 33210059; PMCID: PMC7653638.
- Hagan AS, Zhang B, Ornitz DM. Identification of a FGF18-expressing alveolar myofibroblast that is developmentally cleared during alveologenesis. Development. 2020;147(2):dev.181032 PubMed PMID: 31862844; PMCID: PMC6983722. https://www.ncbi.nlm.nih.gov/pubmed/31862844
- Dorry SJ, Ansbro BO, Ornitz DM, Mutlu GM, Guzy RD. FGFR2 Is Required for AEC2 Homeostasis and Survival after Bleomycin-induced Lung Injury. Am J Respir Cell Mol Biol. 2020;62(5):608-21 PubMed PMID: 31860803; PMCID: PMC7193788. https://www.ncbi.nlm.nih.gov/pubmed/31860803
- McKenzie J, Smith C, Karuppaiah K, Langberg J, Silva MJ, Ornitz DM. Osteocyte Death and Bone Overgrowth in Mice Lacking Fibroblast Growth Factor Receptors 1 and 2 in Mature Osteoblasts and Osteocytes. J Bone Miner Res. 2019;34(9):1660-75 PubMed PMID: 31206783; PMCID: PMC6744314. https://www.ncbi.nlm.nih.gov/pubmed/31206783
- Guzy RD, Li L, Smith C, Dorry SJ, Koo HY, Chen L, Ornitz DM. Pulmonary fibrosis requires cell-autonomous mesenchymal fibroblast growth factor (FGF) signaling. J Biol Chem. 2017;292(25):10364-78 PubMed PMID: 28487375; PMCID: PMC5481550. https://www.ncbi.nlm.nih.gov/pubmed/28487375
- Karuppaiah K, Yu K, Lim J, Chen J, Smith C, Long F, Ornitz DM. FGF signaling in the osteoprogenitor lineage non-autonomously regulates postnatal chondrocyte proliferation and skeletal growth. Development. 2016;143(10):1811-22 PubMed PMID: 27052727; PMCID: PMC4874483. https://www.ncbi.nlm.nih.gov/pubmed/27052727
- Hung IH, Schoenwolf GC, Lewandoski M, Ornitz DM. A combined series of Fgf9 and Fgf18 mutant alleles identifies unique and redundant roles in skeletal development. Dev Biol. 2016;411(1):72-84 PubMed PMID: 26794256; PMCID: PMC4801039. https://www.ncbi.nlm.nih.gov/pubmed/26794256