David Sherwood, Biology

My group is interested in understanding the mechanisms that regulate the ability of cells to invade through basement membranes. Cell invasion is crucial for many developmental processes and human diseases, and remains the least understood aspect in the progression of metastatic cancer. An understanding of the mechanisms that control cell invasion has been limited by the lack of in vivo models where the interactions of the invading cell and basement membrane can be visualized and genetically dissected. Anchor cell invasion into the vulval epithelium in the nematode Caenorhabditis elegans represents a new model where such analysis is possible. Connection of the uterus and vulva in C. elegans is initiated by the uterine anchor cell, whose basolateral portion crosses the basement membranes separating both tissues, and then invades between the central vulval cells. Anchor cell invasion is regulated by: (1) the precise removal of the basement membranes by the anchor cell during invasion; (2) a diffusible cue generated by the central vulval cells that stimulates and targets anchor cell invasion; (3) production of mesenchymal-like invasive protrusions from the basolateral region of the anchor cell. Our group utilizes genetic, genomic and cell biological approaches to identify and characterize the regulatory networks that control anchor cell invasion. Initial studies indicate that many of these mechanisms are conserved with vertebrate cell invasion in development, as well as in cancer progression. Specific projects in the lab include: 1) Identifying Fos-1 transcriptional targets that promote basement membrane removal during invasion, (2) time-lapse analysis of anchor cell invasion using GFP variant tagged anchor cell and basement membrane components, (3) characterizing new genes recently identified as promoting anchor cell invasion and whole genome RNAi and EMS screens to identify additional genes, (4) understanding basement membrane composition and the regulation of invasive-behavior, (5) investigating the evolution of cell-invasive mechanisms, and (6) identifying and characterizing additional cell-invasion events in C. elegans development.