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Melanie Bilodeau

Melanie Bilodeau

Molecular pathways regulating lung epithelial differentiation

Lung buds
In vitro differentiation time-course of mouse lung bud explants placed on floating disks in serum-free media: Day 0 to Day 5

Human pulmonary diseases affect individuals from a wide age spectrum: neonatal respiratory distress syndrome, cystic fibrosis, lung obstructive diseases, lung cancer, etc. These pathologic states are currently under investigation but the limited knowledge of normal lung biology restricts comparative studies and the elaboration of specific treatments. In addition, the promising differentiation of embryonic stem cells and induced pluripotent cells into lung progenitor cells is expected to be priceless for modeling human diseases and for therapeutic purposes, but the efficiency of differentiation protocols need to be drastically improved.

The general goal of my project is to understand the molecular mechanisms regulating the specification, the proliferation and the differentiation of lung epithelial progenitor cells during embryogenesis and adult homeostasis, aiming both to enrich knowledge regarding normal lung biology and to guide the in vitro generation and maintenance of lung progenitors from pluripotent cells. According to this objective, I will characterize the functions of candidate transcription factors involved in lung biology, such as the Thyroid transcription factor 1 (Titf1) encoded by the gene Nkx2.1, using genetic and biochemical approaches applied to mouse and human embryonic stem cells as well as mouse models.