Research over the past three and a half decades has placed the Fuchs’ laboratory squarely within the realm of focusing on how stem cells function in normal homeostasis and wound-repair, and how these fundamental processes go awry in malignant progression. We’ve developed a complex framework of how stem cells receive extrinsic signals from their microenvironment, how these signals lead to changes in chromatin-remodeling, and transcriptional and translational landscapes and how this results in ensuing dynamics of the cytoskeleton and its adhesive contacts. The outcome of these pathways are the changes in cellular growth, migration and differentiation that are necessary to form tissues, regenerate them and repair them, and our research brings us increasingly closer to an understanding of these processes.
As we probe into the mechanisms underlying tissue biology, so too are we unearthing an understanding of how alterations in these basic processes arise during tumorigenesis. With our newfound knowledge of the molecular differences between normal and cancerous stem cells, we can now begin to dig further into how the niche and its stem cell residents change during malignant progression, and how increasingly aberrant crosstalk between the stem cells and their microenvironment leads to a rewiring of the molecular behavior of these tumor-initiating cells. With our newfound ability to carry out complex genetic screens on a large scale level, our functional approaches have been accelerated to take full advantage of the rapid progression of the genome era. As new technologies continue to emerge, our ever improving strategies should keep pace in this arena of excitement.
We've identified a unique signature for cancer stem cells of SCCs, distinct from the normal stem cells of the skin. This now provides a plethora of new information about the nature of these abundant cancers, and serves as a major avenue for future study. Similarly, we are interested in how cancer hijacks the basic mechanisms that all adult stem cells need to make and repair tissues. We will continue to use our expertise in mouse genetics, knockdown/knockout and signaling/chromatin/transcriptional/translational profiling, as well as adapt and develop new technologies to elucidate the underlying mechanisms involved in wound-repair and cancers. Our ultimate goal is to exploit this information to develop small molecule targets directed towards SCCs, the most common and life-threatening cancers world-wide. Understanding the complexities of wound-repair, tumor development and malignant progression in the skin has become a major direction of my group.