My long-term career goal is to become a faculty member at an academic center where I will investigate the contribution of microRNAs (miRNAs) to ovarian cancer metastasis. My current career goals are to build an independent research program in the control of ovarian cancer gene regulation, gain the skills I need to be an independent scientist, and acquire the mentorship and teaching skills necessary as faculty member. I am conducting my research in the lab of Dr. Laurie Hudson at the University of New Mexico where we have access to state-of-the-art genomics, microscopy, and flow cytometry resources. UNM is a NCI designated Cancer Center and home to diverse group of investigators whose collaborative and multi-disciplinary efforts generate a rich research environment. Based on her strong background in research education, Dr. Hudson's lab at UNM is the ideal environment to support by transition to a faculty position. My project objective is to understand how regulation of miRNAs contributes to ovarian cancer metastasis. The epidermal growth factor receptor (EGFR) is associated with advanced ovarian cancer, regulates cell invasion, and promotes broad changes in gene expression. Therefore, I will investigate regulation of miRNAs by EGFR signaling in the metastatic progression of ovarian cancer. I hypothesize that EOF receptor signaling promotes ovarian cancer invasion by coordinately regulating a cohort of miRNAs including miR-125a at the transcriptional level. I determined that EGF treatment reduces mir125a expression and miR-125a regulates metastasis relevant targets in ovarian tumor cells. The following specific aims will test the hypothesis: 1) investigate how EGFR signaling transcriptionally regulates miRNA expression in ovarian tumor cells, 2) evaluate the contribution of miR-125a to invasive potential by regulating invasive targets, and 3) analyze human tumors and malignant ascites for miR-125a expression to establish whether the expression of miR-125a is altered in ovarian cancer. These novel studies will provide evidence for a functional role for miRNAs in ovarian cancer. Relevance: The vast majority of women diagnosed with ovarian cancer have advanced metastatic disease (>70%) leading to poor prognosis. The EGFR pathway is strongly associated with poor patient outcome. Understanding how microRNAs uniquely regulated in cancer (through pathways such as EGFR) function in promoting tumor progression will enable development of novel diagnostic and therapeutic targets.
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