Mechanical regulation of intestinal organoids
Intestinal organoid is selected as a model for the study of organ-level mechano-regulation, which involves multiple types of cells and self-organized distributions of physical stresses. First, we are developing technology to probe the physical properties of live cells in situ with spatial-temporal resolution. Secondly, we study certain parameters of cellular physical properties, including cell volume and molecular crowding. On molecular level, we explore how the changes in cellular physical properties affect the rate and equilibrium of biochemical/biophysical processes, including signaling transduction (e.g.: wnt/β-catenin pathway), phase separation, and signalosome formation. On tissue level, we study the functional consequences of the above-mentioned processes, such as the self-renewal of stem cells, reprogramming of intestinal organoids. Finally, we are applying single-cell sequencing to globally track the cell fate changes in every types of intestinal cells, emphasizing the ecological impact of mechanical stresses on all components in organoid systems.
Tumor-adipose diassembloid
Mammary cancer is one of the most common cancer in women. Tumor progression and metastasis not only are driven by the state of the cancer cells independently but also are notably affected by its interactions with the complex heterogeneous ecosystem surrounding it. Adipocytes constitute a major component of the breast stroma and have garnered attention owing to the significant emerging evidence demonstrating a reciprocal metabolic adaptation between them and the breast cancer cells. We are developing both mammary tumor model and tumor-adipose coexisted 3D ex vivo model, where we assemble tumor spheroid with adipose spheroid using microchip technology. We are particularly interested in the mechanical interplays between tumor cells and adipocytes, out of the widely studied metabolic crosstalks. These mechanical interplays include the direct cell contraction, elevated osmotic pressure, and stiffened matrix. We study the changes happened in adipocytes, including nuclear deformations, reprogramming, and myofibrogenic transdifferentiation. We also study the impacts on caner cells themselves, including their progression and metastasis. In addition, how local mechanical environments regulate the exosome production of cancer cells is also one of our focus.
