The Ornitz laboratory studies the in vivo functions of Fibroblast Growth Factors (FGFs) and their interactions with other signaling pathways. We use engineered mouse models and organ/cell culture to study mechanisms of organogenesis. We apply our knowledge of development to understand how growth factors regulate tissue homeostasis, and how reactivation of developmental programs function in tissue regeneration and injury response.

CARDIOVASCULAR SYSTEMWe are investigating cardioprotective and reparative functions of FGF receptor signaling in cardiomyocytes and endothelial cells in response to ischemia-reperfusion injury and heart failure with preserved ejection fraction (HFpEF).

RESPIRATORY SYSTEM: We are investigating how FGF signaling pathways regulate postnatal alveologenesis, a process that is critical for maturation of a functional gas exchange organ. Defects in alveologenesis occur in premature birth and bronchopulmonary dysplasia. We also study the mechanisms by which FGFs are protective in lung epithelial repair in response to injury.

PULMONARY HYPERTENSION:  We are investigating how FGF signaling in endothelial cells and vascular smooth muscle is protective for hypoxia-induced pulmonary hypertension, a potentially fatal condition that affects premature infants.

SKELETAL SYSTEM: We are investigating how FGF signaling regulates stem cell niches in developing bone and osteoblast and osteocyte function and homeostasis during postnatal bone growth and aging. We are also investigating how FGF signaling in the skeletal vasculature regulates postnatal bone growth and joint homeostasis.

ENDOCRINE FGF FUNCTION:  We are investigating a rare insulin resistance syndrome, Insulin-mediated pseudoacromegaly (IMPA), that leads to overgrowth and tall stature. Sequencing an IMPA patient identified mutations in Fibroblast Growth Factor Receptor 1 (FGFR1) and beta-Klotho (KLB), which form the receptor complex for FGF21, an endocrine hormone that promotes insulin sensitivity in adipose tissue by increasing glucose uptake and suppressing lipolysis.