Research Abstract:
In general, we are interested in understanding how extracellular signals, including cell adhesive events, are transduced inside cells to influence the cellular cytoskeleton so as to effect cell motility. Our approach to this problem has been biochemical, cell biologic, genetics, and cellular imaging – both static and dynamic and in 2- and 3-dimensional systems. We are developing computational models of signaling pathways that regulate cell migration and are amenable to experimental manipulation, so as to identify and quantify interactions between these processes during cell migration. Epithelia are cellular barriers that protect our bodies (inside and out) from environmental insults. Their development, organization, and maintenance are critical for normal homeostasis. We are interested in understanding how epithelia form and remodel during development, how they are organized, and how they are maintained in the adult. Our approach to this problem is cell biologic and genetic. To do so we make use of multiple organisms (Xenopus, drosophila, and mouse). During epithelia-derived cancer invasion (metastasis), early tumors de-adhere from one another and acquire the capacity to migrate or invade through the basement membrane, leading to spread throughout the body. This process has been morphologically, functionally, and genetically described as an epithelial-mesenchymal transition or EMT. While EMT is a normal process during development, in the adult it occurs in pathologic conditions such as organ fibrosis in response to injury, and cancer metastasis. We are interested in understanding the molecular and cellular mechanisms regulating EMT. Specifically, how cell surface adhesive events communicate with nuclear responses to initiate, maintain, and terminate EMT changes.
Selected Publications:
Warner SJ and Longmore GD. Cdc42 Antagonizes Rho1 Activity at Adherens Junctions to Limit Epithelial Cell Apical Tension. J. Cell Biol. 2009 (In Press).
Warner SJ and Longmore GD. Distinct Functions for Rho1 in maintaining adherens junctions and apical tension in remodeling epithelia. J. Cell Biol. 2009 185(6):111-25.
Bajpai S, Correia J, Feng Y, Figueiredo J, Sun SX, Longmore GD, Suriano G, and Wirtz D. Alpha-catenin mediates initial E-cadherin-dependent cell-cell recognition and subsequent bond strengthening. Proc. Natl. Acad. Sci. (USA) 2008 105(47):18331-6.
Sharp TV, Al-Attar A, Ding L, DFoxler DE, de A. Vallim TQ, Zhang Y, Nijmeh HS, Webb TM, Nicholson AG, Q. Zhang Q, A. Kraja A, I. Spendlove I, J. Osborne J, E. Mardis E, and G.D. Longmore GD. The chromosome 3p21.3 encoded gene, LIMD1, is a critical tumor suppressor involved in human lung cancer development. Proc. Natl. Acad. Sci. (USA) 2008 105(50):19932-7.
Langer EM, Feng Y, Zhaoyuan H, Rauscher III FJ, Kroll KK and Longmore GD. Ajuba LIM proteins are Snail/Slug corepressors required for neural crest development in Xenopus. Developmental Cell 2008 14(3):424-36.
Last Updated: 09/10/2009 |