We are studying the dynamic interactions between non-epithelial cells in tissues that interface with the environment. Using multi pronged approaches including mouse genetics, cell culture models, genomics and microscopy, we tackle complex biological processes focusing on the contribution of cell-intrinsic and cell-extrinsic factors that contribute to regenerative processes. By leveraging the abundant clinical resources of the Yale medical center and our colleagues in basic stem cell, cell biology, and engineering, we are uniquely able to address clinically relevant questions that have been unexplored for decades.
Epithelial tissues are composed of epithelial cells that create a barrier against the environment and are supported by a plethora of stromal cells like fibroblasts, adipocytes, immune cells, and endothelial cells. The identity and function of many stromal cell types is unknown and may hold the key to therapeutic avenues for chronic injuries and cancer.
Our lab develops and applies novel, interdisciplinary techniques to follow, track, and modulate cells and molecules within tissues and define their function in epithelial tissues. We build new conceptual frameworks to integrate specific cell types with tissue resident cells, and repurposing of techniques from cell, developmental, and chemical biology. As a result, we build, pilot, and collaborate to assemble the tools necessary to tackle the biggest questions in tissue repair and epithelial biology. Specifically, we are interested in identifying the cellular and molecular mechanisms by which adipocytes, endothelial, and immune cells function in tissue repair and tumorigenesis. We are intrigued by the function of lipids within epithelial tissues and their role in inflammation, fibrosis, and tumorigenesis.
A major innovative aspect of our work has been the study of mesenchymal cells: fibroblasts and adipocyte stem cells in barrier tissues.
Recently identified functionally heterogeneity in myofibroblast subsets in their production of extracellular matrix molecules. Our future work will define how ECM homeostasis is regulated and contributes to tissue repair.
Physical forces and the architecture of the extracellular environment are an emerging area of cell fate regulation and tissue homeostasis.
Cells sense changes in their physical environment through cell-cell and cell-extracellular matrix (ECM) adhesions and these mechanical inputs can control cell fate. However, how these geometrical and physical inputs regulate cellular processes is not well understood. We are leveraging the skin as a model to explore these questions by defining how mechanical inputs regulate cell fate and tissue homeostasis.