Dr. Xiuxia Zhou’s Research
Dr. Zhou’s research work has been focused on the signaling pathways related to extracellular matrix turnover and the role and function of chemoattractant molecules in primary human lung fibroblasts. Specifically, her work involves:
- Cellular responses to IL-13 and TGF-β in fibroblasts during lung inflammation and repair in asthma. Dr. Zhou’s studies focus on the TGF-β and IL-4Rα signaling pathways on extracellular matrix metabolism, airway inflammation and remodeling in primary human fibroblasts obtained from normal and asthmatic subjects.
- Regional fibroblasts heterogeneity in asthma. Dr. Zhou has been interested in regulatory mechanisms that determine the differences between fibroblasts isolated from proximal and distal lung. Dr. Zhou has successfully transfected primary human lung fibroblasts with dominant negative constructs or siRNA, and would like to fully understand the mechanisms controlling their phenotypic differences using an epigenetic approach.
IL-4/13 acts through IL-4Rα, and transducts the signaling through STAT6, MEK-ERK and PI3K/Akt pathways. TGF-β could activate both Smad and JNK, as well as MEK-ERK. Crosstalk exists between IL-13 and TGF-β triggered pathways and contributes to asthma-associated gene transcription and regulation. For example, TIMP-1 is mainly induced by TGF-β, but IL-13 augments the effect; eotaxin-1 is mainly induced by IL-13, but it was synergistically increased by the addition of TGF-β. The mechanisms behind of the synergy were investigated.
Morphologic differences between primary airway and distal lung fibroblasts from the same subject with asthma taken at an original magnification of x200. The phenotypic differences may partially explain the variable responses to injury and repair between proximal airways and distal lung in asthma and other respiratory diseases.
Acetylation plays a major role in the highly regulated gene transcription in eukaryotes. Histone deacetylation is associated with transcriptional repression reversing the chromatin remodeling process. In general, the deacetylation of histones (by HDACs) results in transcriptional repression, whereas increases in histone acetylation (by HATs) lead to the enhancement of gene transcription. Epigenetic study is a better approach to further understand different gene expression in proximal and distal lung fibroblasts, such as SMA, procollagen.