Our long-term goal is to elucidate the cellular and molecular mechanisms that regulate cell invasion through basement membrane, the dense, highly cross-linked, sheet-like extracellular matrix that underlies most cells and tissues.  During development and in normal physiological processes specialized cells acquire the ability to cross through basement membrane to disperse (neural crest, germ cells, myoblasts, leukocytes) and to form organs (capillary tip cells, cytotrophoblasts).  This same invasive behavior is co-opted by metastatic cells, which accounts for the poor prognosis with most lethal forms of cancer.

Despite profound importance, the mechanisms underlying cell invasive behavior remain poorly understood.  In development and cancer, cell invasions are dynamic and occur in visually inaccessible environments, and thus it has been remarkably difficult to study.  To gain insights into cell invasive behavior, our group is analyzing anchor-cell (AC) invasion into the vulval epithelium in Caenorhabditis elegans,  a simple, experimentally accessible cell invasion event.  Connection of the uterus and vulva in C. elegans is initiated by the uterine AC, which invades through two basement membranes to establish contact with the central vulval cells.  Our lab combines single-cell visualization with forward genetic and functional genomic approaches to understand the fundamental mechanisms that control cell invasive behavior.  Ultimately, it is our goal to apply what we learn from C. elegans towards new therapeutic strategies to block or regulate cell invasion in development and cancer.

We are very grateful to the March of Dimes, American Cancer Society, Pew Foundation, Damon Runyon Cancer Research Foundation, Duke University and the National Institutes of Health for supporting our research.