Lung Stem Cells and Directed Morphogenesis. We are interested in understanding and engineering the cellular and extracellular niches governing the induction of mature lung cells from human induced pluripotent stem cells (hiPSCs) and resident lung stem cells. Our ultimate goal is to use engineering approaches to guide directed morphogenesis of functional lung tissues for applications in regenerative medicine and disease modeling. While most existing hiPSC differentiation models focus on studying one parenchymal lineage at a time, we intend to study how inter-organ cellular crosstalk modulates the respective organogenesis and maturation of participating lineages. In particular, we have established a strategy for simultaneous induction of endoderm-derived lung and mesoderm-derived heart lineages from a single hiPSC culture, which provides an unprecedented opportunity to investigate cardiopulmonary co-development and segregation during human embryogenesis (Ng WH, et al. 2021).
Engineering and Tracking the Extracellular Matrix. The extracellular matrix (ECM) is a ‘nest’ built by cells for themselves to survive, function and communicate, and is the foundation of multicellular organisms. The native ECM is thus a natural scaffolding material for supporting stem cells and engineered tissues. We have a long-term interest in deriving functional ECM materials that carry tissue-specific cues and in further functionalization of these materials in a chemoselective manner to endow them with novel functionalities without changing their bulk properties. To enable this effort, we have developed a metabolic glycan engineering strategy for biocompatible incorporation of click chemistry-reactive ligands into the native ECM of a wide variety of tissues and organs both in vivo and ex vivo (Ren X et al., 2018; Ling Z et al., 2021), offering a platform technology for native ECM biomaterial functionalization. In parallel, we are developing proteomic pipelines for ultrasensitive tracking of ECM synthesis with the goal of capturing the dynamics of the extracellular microenvironment along organogenesis and pathogenesis (fibrosis, hypertension and cancer).
Chemoselective Engineering of Cellular Membranes and Glycocalyx. The lipid bilayer membrane is a commonly used building block by cells to establish boundaries/compartments within (organelles), across (plasma membrane) or outside (extracellular vesicles) the cell. Most of these membrane structures are polarized with one side being heavily decorated with glycan- and protein-rich polymer coatings (i.e. the glycocalyx). We are developing approaches and tools to facilitate the access and assessment of membrane surface glycocalyx. Using metabolic glycocalyx engineering, we are also making efforts to functionalize these membrane surfaces to enable controlled interfacing between cells, between cells and nanomaterials (Wijesekara P et al., 2021; Liu Y et al., 2021; in collaboration with Taylor Lab), and between cells/cell-derived vesicles and ECM materials.