Regulation of Angiopoietin mRNA Stability

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DESCRIPTION (provided by applicant): A five year training program of integrated didactic and laboratory experiences to facilitate the development of an academic career involving molecular biology based research. The principle investigator has successfully completed a residency in Anatomic and Clinical Pathology and is currently in a two-year Molecular Genetic Pathology Fellowship. To build toward the goal of obtaining a tenure track position in an academic setting, and to combine a career in both basic research and academic medicine, the choice was made to obtain education and experience in molecular biological research involving angiogenesis and its role in diseases of the eye. This goal will be accomplished through a challenging research proposal focused on signal transduction pathways associated with Angiopoietin-2 (Ang2) mRNA stability. Ang2 is critically involved in blood vessel stability, and is involved in ocular neovascularization. Preliminary data indicate that Ang2 is significantly regulated post-transcriptionally, and that phosphoinositide-3-kinase (PI3K) activity plays a critical role in Ang2 mRNA stability. We will identify cis-acting elements in Ang2 mRNA and the associated trans-acting factors involved in PI3K-mediated Ang2 mRNA stability. Drs. Anderson (Mentor - Chair of the Department of Cell Biology) and Howard (Co-Mentor - Associate Professor of Cell Biology) have extensive research experience in the fields of eye disease (including the role of PI3K in ocular disease) and angiogenesis (including the regulation angiopoietins), respectively. The University of Oklahoma Health Sciences Center is strongly committed to ocular research through the Dean McGee Eye Institute. The facilities available to the principal investigator provide the modem equipment necessary for this level of molecular-based research.