My career goal is to develop an independent research program at an academic institution uncovering the genetic pathways that control cell invasion in order to reveal new targets for therapy aimed at halting the malignant progression of cancer. Towards this goal, I have developed cell biological assays to characterize the process of anchor cell (AC) invasion into the vulval epithelium in the C. elegans larva. I have found that AC invasion shares all of the same steps in the invasive process as human metastatic cancer cells, and have recently identified the C. elegans homolog of the fos proto-oncogene and netrin signaling as critical regulators of AC invasion. To fully develop this process as a model for understanding cell invasion in vivo, new tools must be generated to address how genes function during AC invasion, and genomic methods learned to uncover the many additional genes that regulate this process. Two years of mentored work are thus proposed under the guidance of Professor Paul Sternberg at the California Institute of Technology to collaborate with a major study in the laboratory to develop AC and vulval specific promoters to drive transgenes. These tools will be used to determine the function of Ce-fos in AC invasion. Genomic approaches will also be developed by learning techniques for constructing single cell cDNA libraries, screening a full genome RNAi library for genes controlling AC invasion, and learning methods for targeted gene knockout. Interactions with members of WormBase (the international C. elegans database at Caltech) will be invaluable as I develop these genomic approaches. During three years of independent research, these new tools will be used to examine the function of netrin signaling and genes isolated with the RNAi screen, to order these genes into genetic pathways, and to examine how separate pathways interact to coordinate distinct steps in AC invasion. Furthermore, single cell DNA microarray approaches will be developed to determine changes in gene expression in different mutant backgrounds and distinct developmental stages to gain a more complete understanding of the genes that regulate AC invasion. ? ?
Showing the most recent 10 out of 11 publications
