Dr. Zhou's research focuses on the mechanobiology of lung repair and regeneration. Stiffening of the extracellular matrix (ECM) is a cardinal feature of human idiopathic pulmonary fibrosis (IPF). Studies from Dr. Zhou’s laboratory demonstrated that biomechanical signals from the stiffened fibrotic ECM promote lung myofibroblast differentiation (Huang et al, AJRCMB 2012; Zhou et al, JCI 2013), fibroblast migration (Guo et al, JCI Insight 2023) and invasion into the basement membrane (Chen, Qu et al, Nat Commun 2016), and IPF-associated gene expression in both lung fibroblasts (Zhou et al, JCI Insight 2020) and alveolar epithelial cells (Qu et al, AJRCCM 2018). Preclinical studies in experimental lung fibrosis models showed that targeting aberrant mechanical signaling inhibits the profibrotic phenotype of lung cells and promotes lung fibrosis resolution in mice (Qu et al, JEM 2021, Chen, Qu et al, Nat Commun 2016, Zhou et al, JCI 2013). Dysfunction of lung stem/progenitor cells impairs lung tissue regeneration following injury, contributing to pulmonary fibrosis. Stem cells are known to reside in a specialized microenvironment known as the stem cell niche. The stem cell niche provides instructive cues for stem cell self-renewal and differentiation. Current studies in Dr. Zhou’s laboratory aimed to determine the role of mechanical microenvironment (mechano-niche) in the regulation of lung stem/progenitor cell properties and niche cell fate, and to test the therapeutic potential of targeting mechano-niche in reinstatement of the regenerative propensity of lung stem cells and the reversal of pulmonary fibrosis.
