Dr. George T. Eisenhoffer, Jr.
The University of Texas MD Anderson Cancer Center
Department of Genetics
Epithelial tissues provide an essential protective barrier for the organs they encase, and are also prone also the primary sites where most solid tumors or carcinomas form. Cells comprising epithelial tissues are continually being eliminated by apoptosis and replaced by cell proliferation. Alterations in both cell loss and division have been implicated in numerous human diseases, including cancer, yet our understanding of how these processes are coordinated to control overall numbers within normal epithelia remains limited. The goal of the research in my laboratory is to elucidate the mechanisms that regulate epithelial cell turnover while preserving barrier function. Our work has uncovered that mechanical forces guide the inter-relationship between cell death and division during homeostatic cell turnover in epithelia, and that damage elicits a separate but equally important response. We have found that cell extrusion, a process used to eliminate cells from epithelia without disrupting barrier function, is the key to driving turnover in both scenarios. To investigate extrusion in a living epithelial tissue, we have developed a cell and molecular toolset for the epidermis of developing zebrafish. This system now provides unparalleled access to analyze epithelial cell turnover in vivo in real time. Students will utilize a combinatorial approach that involves time lapse imaging and reverse genetic techniques to characterize cell turnover under physiological conditions, after damage, and when extrusion is perturbed to gain a better understanding of how specific alterations may lead to epithelial pathologies and cancer.