Research

Cell-cell crosstalks

Paracrine signals are enriched in the vascular microenvironment and are pivotal for regulating vascular homeostasis. We previously developed comprehensive computational tools to study the cell-cell crosstalk signals in the human lung capillary using single-cell RNA-seq. Leveraging this tool, we have identified several important locally acting cell-cell crosstalk soluble factors in a functional lung microvascular niche. These local paracrine signals have the potential to 

1) induce in vitro vascular maturation and improve the fidelity of current bioengineered lung vascular model systems 

2) improve vascular repair during injury and have translational potential for the treatment of lung vascular diseases.

Cell-ECM interactions

Extracellular matrix (ECM) is a collection of extracellular molecules that provide structural support and regulate cell adhesion and cell signaling. Whole organ decellularization opens the door to developing a construct that recapitulates a complete native ECM microenvironment. We previously used quantitative proteomics to examine ECM components remaining after decellularization in rat and human lungs and showed an intact vascular architecture and near-native retention of ECM components after decellularization. We further cultured human epithelial and endothelial cells into the decellularized lungs and found that epithelial stem cells or endothelial cells cultured in these decellularized tissue constructs took on phenotypes of their native counterparts, suggesting the potential of this using platform for disease modeling applications. Leveraging decellularization/recellularization method, in this future, we will 

1) Delineate the molecular mechanisms of native cell-ECM interactions on vascular functions.

2) Reconstruct cell-ECM interactions in vitro to develop vascular or vascularized tissue model system.