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Vanderbilt-Ingram Cancer CenterVanderbilt-Ingram Cancer Center

Alissa  Weaver

Alissa Weaver, M.D. , Ph.D.

Associate Professor of Cancer Biology, Pathology
VICC Member

Contact Information:

Vanderbilt University Medical Center
448 Preston Research Building, 2220 Pierce Avenue
Nashville, TN 37232-6840
Fax: 615-936-2911

Research Specialty

Dynamic actin assembly for cell motility and cancer metastasis.

Research Description

Cell motility is important for a number of physiologic and pathologic processes, including wound healing, immune system function, axon guidance, and cancer cell metastasis. In order for a cell to move, it must rapidly rearrange its actin cytoskeleton to produce the required cell shape changes and to generate force. Among the various forms of actin structures in cells, the most dynamic (assembled and disassembled in a matter of seconds) are the branched actin filament networks nucleated by the Arp2/3 protein complex. Arp2/3 complex is essential for plasma membrane protrusion at the leading edge of migrating cells and is also important in such processes as endocytosis, cell-cell junction formation, and the formation of subcellular structures used for cancer cell invasion (invadopodia).

Activation of Arp2/3 complex in cells occurs in response to a variety of signals, including from growth factors, src family kinases, and rho GTPases. Cellular activators include members of the Wiskott-Aldrich Syndrome family of proteins (WASps) and cortactin, a src kinase substrate that is overexpressed in a number of epithelial cancers. A major goal of the laboratory is to understand how Arp2/3-activators and associated signaling molecules contribute to cell motility and cancer invasion. We use a variety of techniques including siRNA, live-cell imaging, and biochemistry. Specific projects include: 1) cortactin and WASp family function in lamellipodial protrusion and cell motility; 2) actin assembly in membrane trafficking and autocrine secretion; 3) role of cortactin in head and neck squamous carcinoma progression; 4) molecular regulation of invadopodia; 5) determining critical parameters for invasion of breast cancer cells in three dimensions; and 6) interdisciplinary projects focused on mathematical modeling of cancer invasion.

Figure 1: Breast cancer cell stained with rhodamine-phalloidin to reveal filamentous actin (left panel) at sites of invasion into fluorescent basement membrane (middle panel: FITC-fibronectin). Right panel: merge of images.

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