The goal of these studies is to identify the mechanisms that regulate the lung mesenchymal stem cell (MSC) compartment in the distal lung. We therefore hypothesize that the maintenance of lung MSC function by Wnt/β-catenin signaling is necessary for pulmonary tissue homeostasis.
Lung MSC regulate Angiogenesis and Repair during Fibrosis
Loss of ABCG2 MSC function drives microvascular dysfunction and exacerbates pulmonary fibrosis. The goal of our studies is to identify the mechanisms that regulate the ABCG2 lung mesenchymal stromal cell (MSC) compartment and underlying development of associated microvascular dysfunction in the presence of fibrosis. Understanding the aforementioned processes are crucial to our knowledge of the role lung MSC play in the maintenance of pulmonary microvascular homeostasis and tissue structure, repair and disease as well as the identification of directed therapies targeting this specific cell type.
Adult Mesenchymal Progenitor (MPC) Regulation of Early Pathogenesis in TSC
Our proposed studies are designed to provide a novel understanding of the cell-based mechanisms initiating smooth muscle cell (SMC) accumulation and lesion formation during the development of TSC. We have recently identified a specific population of mesenchymal progenitor cells (MPC) in the adult human and murine lung that regulate SMC function. We will exploit our human and mouse models to define a role for MPC in the regulation of the lesion microenvironment during the development of TSC.