The lung can be compartmentalized into the proximal conducting airways and the distal alveoli, each employing distinct stem/progenitors to support the divergent roles of each sub-compartment. An emerging paradigm is that the underlying stroma engages in complex feedback loops with the stem/progenitors to modulate their behavior. Despite their homogeneity in appearance, it is increasingly apparent that the lung stroma contains diverse subsets, each uniquely suited to maintain the nearest stem/progenitor population. Utilizing sophisticated mouse genetic models, population and single cell RNA sequencing, and human tissue studies, our lab is investigating how segregated stromal identities are maintained in distinct locales and context, and how disruption of those stromal identities can lead to human diseases.
Establishment of organoid culture system to study tissue-tissue interaction
Our lab is interested in dissecting paracrine interactions that maintain normal tissue homeostasis, and modeling these behaviors in vitro. We have established organoid culture systems to study how various stromal subsets support epithelial stem/progenitors with both mouse and human derived samples. The goal is to identify stromal-derived factors that regulate epithelial stem/progenitor behavior and vice versa.
Developing single-cell pipelines to dissect Stromal heterogeneity
We are focused on understanding how certain developmental pathways subdivide stromal subpopulations based on location and function. We are performing single-cell RNA sequencing using both the 10X Genomics and C1 Fluidigm platform to better understand how stromal transcriptomes segregate based on location and cellular behavior in mouse and human.
Characterizing accelerated aging models
We have developed genetic tools to accelerate aging in the mesenchymal compartment in a temporal and spatially-selective manner. The goal is to identify tissue responses to the aging mesenchymal niche and evaluate factors that drive the aging phenotype.