Our laboratory is interested in studying how key developmental pathways continue to persist in adulthood to maintain normal homeostatic organ function. We are particularly focused on the mesenchymal cell types (e.g. fibroblasts, pericytes, and etc.) that are poorly understood and lack precise anatomical definition, but are integral to the structural integrity and function of adult organs such as the lung.
Previous work focused on how the Hedgehog pathway directed mesenchymal progenitor differentiation during embryonic development, and much to our surprise, how Hedgehog continues to maintain normal mesenchymal homeostasis during adulthood. We found that cellular quiescence in the adult lung is not a default state, but rather actively maintained by epithelial-mesenchymal crosstalk coordinated by Hedgehog. This suggests that cellular quiescence is tightly regulated by the state of Hedgehog activation within the mesenchyme to regulate cellular turnover during homeostasis and injury, and that dysregulated Hedgehog signaling could lead to maladaptive remodeling and lung diseases.
Interested BMS/DSCB grad students are always welcome for lab rotations. Possible rotating projects include:
1. 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 mesenchymal niches support epithelial survival and differentiation. The goal is to identify mesenchymal-derived factors that regulate epithelial progenitor behavior and vice versa.
2. Developing single-cell pipelines to dissect mesenchymal heterogeneity. We are focused on understanding how certain developmental pathways subdivide mesenchymal populations based on location and function. We are performing single-cell RNA sequencing using both the Drop-Seq and C1 Fluidigm platform to better understand how mesenchymal transcriptomes segregate based on location and cellular behavior.
3. 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.
