18. GOALS FOR FELLOWSHIP TRAINING AND CAREER My goal for postdoctoral training is to acquire the technical and intellectual skills necessary to study cell migration h4 vivo using C. elegans as a model organism. C. elegans has proven to be an excellent system in which to study cell migration due to its optical transparency, wealth of genetic tools and relative simplicity. As a postdoctoral researcher in Jeff Hardin's laboratory I am being provided with wonderful opportunities to analyze cell migration in C. elegans through genetics, 4D microscopy and RNA interference. This should provide a nice complement to my graduate work which involved studying integrin-mediated regulation of cell migration using a tissue culture system. My career goal is to conduct innovative, high quality research at a research institute or major research university. I plan to study cell migration through a combination of cell biology experiments using cancer-derived cell lines and studies hAvivo, using C. elegans. Understanding how cells migrate will give insights into physiological processes such as development and wound healing and will aid in the design of treatments for diseases that involve aberrant cell migration, such as tumor metastasis. My hope is that the screen described in Aim IlI of my research proposal will yield interesting proteins that will inspire studies to launch my own independent research program. 19. NAME AND DEGREE(S) Jeffrey D. Hardin 20. POSITION/RANK Associate Professor, Dept. of Zoolog,/, University of Wisconsin-Madison 21. RESEARCHINTERESTS/AREAS morphogenesis, cell motility, cell movement, developmental biology _ :_i_._'11 :.[e,]: II 'J={o] '.Zm]._-._. 22. DESCRIPTION (Do not exceed space provided) Misregulation of cadherin-mediated adhesion underlies numerous developmental defects and is a major contributing factor to tumor metastasis. Determining how cadherin-mediated adhesions are regulated is essential for understanding development and will aid in the design of more effective therapies to treat and prevent tumor metastasis. Morphogenesis in C. elegans provides an excellent model system in which to examine the regulation of cadherin-mediated adhesions bz vivo. A cadherin-catenin complex is important for the formation of cell-cell adhesions during the process of epithelial morphogenesis, which involves movement and sealing of epidermal cells to surround the embryo in a continuous layer of epidermis [1-3]. Recent studies demonstrate that the C. elegans homologue of p120 catenin, jac-1, also plays a role in this process [4]. p120 catenin has an important yet poorly understood role in mediating cell-cell adhesion and protrusion [5-12]. Little is understood about the role of p120 catenin in vivo; however, abnormal expression of p120 catenin has been linked to aggressive tumor phenotypes [13- 19]. The goal of this research proposal is to investigate the role of p120 catenin in vivo through examining the cellular and molecular mechanisms through which JAC-1/pl20 catenin regulates cadherin-mediated adhesion during epithelial morphogenesis in C. elegans. This will be accomplished through a combination of genetics, 4D miscroscopy and RNA interference. PHS 416-1 (Rev. 12198) Form Page 2 BB CC Individual NRSA Application NAME(Last,first,middleinitial) Table of Contents ========================================Section End===========================================
| Cox-Paulson, Elisabeth A; Walck-Shannon, Elise; Lynch, Allison M et al. (2012) Tropomodulin protects ?-catenin-dependent junctional-actin networks under stress during epithelial morphogenesis. Curr Biol 22:1500-5 |
| Lynch, Allison M; Grana, Theresa; Cox-Paulson, Elisabeth et al. (2012) A genome-wide functional screen shows MAGI-1 is an L1CAM-dependent stabilizer of apical junctions in C. elegans. Curr Biol 22:1891-9 |
