Mechanisms of Cancer Initiation by TRIM32

Oregon Health & Science University, Portland OR

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): This revised proposal is in response to the opportunity for Enabling RPGs to Leverage NCRR Center and Center-like Programs with the purpose of accelerating the pace of research of our NCI-funded project R01- CA98577-06, "Mechanisms of Cancer Initiation by TRIM32" including key personnel and jobs for informatics and clinical study coordinators. Specifically, the project addresses this opportunity and ARRA criteria to i) connect my laboratory research and Dermatology-based Molecular Profiling Resource (MPR) of oral and skin tumors to a Research Data Warehouse (RDW) created to streamline access to outcomes data through the efforts of NCRR-funded OCTRI (our OHSU CSTA, Eric Orwell, PI) and new co-investigator Shannon McWeeney, who is OCTRI/Knight Cancer Institute liaison, co-director of OHSU Biomedical Informatics Program with OCTRI's Robert Schuff, and who has overseen the Knight's participation in NCI's CaBIG* initiative;and ii) create/retain jobs for support personnel for clinical coordination and bioinformatics. This R01 revision will accelerate translation of our findings on Trim32 scaffold protein and E3 ubiquitin ligase regulation of tumor suppressors (in particular the protein inhibitor of activated STATs (Pias) family of transcriptional repressors of oncogenes) to prognostics of risk of recurrence and treatment response of high risk head and neck and skin squamous cell carcinomas (SCC). The proposal will extend our research to test novel roles of Trim32 in the context of a broader signaling network in the same tissue samples, including Trim32 association with cMyc phosphorylation status and putative miRNA markers of the tumor stem cell, working with new collaborator Dr. Rosalie Sears. This revised one-year plan will leverage the NCRR-funded OCTRI to pursue two new goals: (Goal 1) annotate our MPR tumor tissues for outcomes research, standardizing data elements between our tissue database and the data sources on campus coordinated by OCTRI RDW (such as the Oregon State Cancer Registry (OSCaR) and patient history in OHSU's electronic chart system EPIC), involving intermediate steps that initiate clinical data annotation immediately while standardizing, data cleaning and migrating our tissue database to a more broadly accessible format under the "umbrella" of the OHSU Knight Cancer Institute;and (Goal 2) extend our analysis from retrospective study of ~33 samples to prospective study of 200-400 cases (including patient-matched uninvolved tissue controls) with outcomes data (including recurrence, stable disease, progression, regression, disease-free survival, death with disease, and treatment) to test new hypotheses about association with Trim32, tumor suppressor Piasy and new endpoints of Trim32 association with stabilized cMyc and miRNA in head and neck and skin SCC. * Cancer Biomedical Informatics Grid