David R. Sherwood
Assistant Professor

919-613-8192

FFSC 4216

Dave Sherwood Lab

Research Interests: Genetic analysis of development in C. elegans: modeling cell invasive behavior

The ability of cells to invade through basement membranes that surround tissues 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. We are also interested in gaining an understanding of the evolution of cell-invasive behavior and will be examining anchor cell invasion in different nematode species. Members of our group will be trained in a diverse range of scientific approaches and will join a vibrant scientific community at Duke University, the Research Triangle region and the worldwide group of worm researchers.

Current projects: (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, (6) identifying and characterizing additional cell-invasion events in C. elegans development.

Recent Publications   (More Publications)   (search)

1. DR Sherwood, Cell invasion through basement membranes: an anchor of understanding., Trends Cell Biol, England, vol. 16 no. 5 (May, 2006), pp. 250-6 (ISSN: HASH(0xa943edc).)  [abs].
2. DR Sherwood, JA Butler, JM Kramer, PW Sternberg, FOS-1 promotes basement-membrane removal during anchor-cell invasion in C. elegans., Cell, United States, vol. 121 no. 6 (June, 2005), pp. 951-62  [abs].
3. DR Sherwood, PW Sternberg, Anchor cell invasion into the vulval epithelium in C. elegans., Dev Cell, United States, vol. 5 no. 1 (July, 2003), pp. 21-31  [abs].
4. T Inoue, DR Sherwood, G Aspöck, JA Butler, BP Gupta, M Kirouac, M Wang, PY Lee, JM Kramer, I Hope, TR Bürglin, PW Sternberg, Gene expression markers for Caenorhabditis elegans vulval cells., Mech Dev, Ireland, vol. 119 Suppl 1 (December, 2002), pp. S203-9  [abs].
5. T Inoue, DR Sherwood, G Aspöck, JA Butler, BP Gupta, M Kirouac, M Wang, PY Lee, JM Kramer, I Hope, TR Bürglin, PW Sternberg, Gene expression markers for Caenorhabditis elegans vulval cells., Gene Expr Patterns, Unknown, vol. 2 no. 3-4 (December, 2002), pp. 235-41  [abs].