One of your earliest childhood biology lessons probably occurred when you body demonstrated to you that your skin is an organ that is able to self-regenerate. Indeed wound healing is a fascinating process in which cells carry out a precise and complex choreography that includes cellular differentiation and regulation of gene expression.
Our lab studies a particular cell type called dermal fibroblasts. If a wound occurs, they migrate to the site of injury, change into muscle like cells (myofibroblasts) that contract to help with would closure, and, once the wound has healed, enter programmed cell death to clear the work area. Disruption to this process can result in chronic ulcers or keloid scarring. A major goal of our studies is to understand how the fibroblast to myofibroblast transition is regulated, so that therapeutic strategies can be devised to prevent and treat this pervasive problem.
In addition to our motivation to understand would healing in order to learn how to control it and cure its pathologies, would heating is an accessible system to study more general differentiation events involved in tissue regeneration. By studying the changes that fibroblasts undergo during would healing, we revealed an important mechanism of gene regulation that could help explain more generally how cells maintain a particular identity and how they can be driven to a different state. The molecules we identified are known to control general gen activity as well as the spatial organization of genes within the cell’s nucleus. Moreover during the course of our investigations we showed that the mechanism we originally identified in wound healing is general to many other reprograming processes such as the induced pluripotency.
One of the ways in which our laboratory studies how cells control gene activity is by directly visualizing gene expression. Using high specialized microscopy, biochemistry and computer analysis, we are able to observe the behavior of individual gene regulatory molecules within individual living cells. We have built a new microscope called Lattice Light Sheet microscope that allow us to visualize single proteins movements and binding within the cells of a developing organism. We are testing this system on developing fruit fly embryos and will very rapidly use it to image the molecular processes involved in cell type definition in human developmental systems developed using ES cells. We will continue to use and improve these methods to better understand how genes are controlled. These studies will open the door to new strategies in cellular reprogramming and potentially to new strategies for modifying cells for therapeutic use.