Cellular Interactions in Pulmonary Oxygen Toxicity in Developing Lung: Candidates background: The candidate has been interested in the pathophysiology of pulmonary diseases in children since her fellowship at Columbia University, NY. Since then she has worked in the field of Asthma and interstitial lung diseases in children. With her experience reinforced with her desire to learn basic research, she was awarded NIH training Grant Fellowship at Case Western Reserve University, Cleveland. Expertise in in vitro co-cultures, cell-cell interaction, cell migration, and hyperoxic exposure of neonatal rat pups was developed. Her stay at New England Medical Center further cultivated this in developing lung. Career goals and objectives: Her goal is to pursue a career as an independent Scientific Investigator, she remains deeply committed to Basic Science research as a way to better understand and treat chronic lung diseases in children. The transition from supervised to independent investigator will require additional years of structured training. Environment: The environment has been excellent with readily available critical review of experimental design and results, and assistance with learning the many new technical procedures required for developing expertise in this area of cell-cell interaction in hyperoxic lung injury. The Advisory Committee consists of authorities in Lung Development and Hyperoxic lung injury in New England Medical Center, Harvard University, Boston Medical Center, and NIDDK, National Institute of Health. Hypothesis: Interaction between Insulin-like growth factor-I (IGF-I) and IGF- I receptor (IGF-IR) is an important regulatory mechanism in hyperoxic lung injury in developing lung.
Specific aims : 1. The onset of hyperoxic lung injury in developing lugs is associated with an increase in the expression of IGF-1 in epithelial cells and an increase in the expression of IGF-IR in fibroblasts. 2. IGF-I and IGF-IR interaction regulates epithelial cell- fibroblast communication in hyperoxic lung injury. Induction of fibroblast proliferation and collagen synthesis will be used as evidence of cell-cell interaction using the in vitro and in vivo experiments, and it will be tested by blocking the interaction by various strategies. 3. Retinoic acid decreases the proliferative effect of IGF-I through its action on IGF binding proteins. This mentored work will provide extensive education and technical experience in Molecular Biology and the development of a model of hyperoxic lung injury.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Clinical Investigator Award (CIA) (K08)
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Special Emphasis Panel (ZHL1-CSR-M (F2))
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Colombini-Hatch, Sandra
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Tufts University
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Chetty, Anne; Cao, Gong-Jie; Severgnini, Mariano et al. (2008) Role of matrix metalloprotease-9 in hyperoxic injury in developing lung. Am J Physiol Lung Cell Mol Physiol 295:L584-92
Chetty, Anne; Cao, Gong-Jee; Manzo, Nicholas et al. (2008) The role of IL-6 and IL-11 in hyperoxic injury in developing lung. Pediatr Pulmonol 43:297-304
Chetty, Anne; Cao, Gong-Jee; Nielsen, Heber C (2006) Insulin-like Growth Factor-I signaling mechanisms, type I collagen and alpha smooth muscle actin in human fetal lung fibroblasts. Pediatr Res 60:389-94
Chetty, Anne; Manzo, Nicholas; Waxman, Aaron B et al. (2005) Modulation of IGF-binding protein-2 and -3 in hyperoxic injury in developing rat lung. Pediatr Res 58:222-8