The proposed plan for this NCI Mentored Career Development for Underrepresented Minorities K01 award is a two-year Mentored Phase, followed by a three-year Independent Phase. The Mentored Phase will provide for advanced training for the minority principal investigator under the co-mentorship of Dr. David Wong at the Laboratory of Head and Neck Cancer Research/Dental Research Institute and Dr. Lily Wu at the Vector-based Gene Therapy Laboratory/Crump Institute for Molecular Imaging at UCLA. This phase will provide the candidate with the opportunity to focus her efforts on research and development towards an academic career as an independent scientist. The overall goal of this proposal is to examine the role of p12 CDK2AP11 in regulating normal and neoplastic growth using in vivo model systems. Our rationale is that p12CDK2AP1, a cell cycle regulator and CDK2-associating protein commonly downregulated in -70% of head and neck cancers, is importantly involved in regulating normal and neoplastic growth in vivo. Several studies have shown that reexpressing p12 CDK2AP1 in tumor cells results in growth inhibition and induction of apoptosis, however little is known regarding the role of this molecule in regulating normal cell growth. During the Mentored Phase, the candidate will engage in investigating the role of pi2 CDK2AP1in normal development, and generating novel p12 CDK2AP1-based gene therapies for head and neck cancer treatment. In addition to the research training, a didactic component has been incorporated in the career development plan to enhance the candidate's overall career development. Defined milestones also will be in place to assess the candidate's scientific progress, particularly during transition to the Independent Phase. During the Independent Phase, the candidate will engage in examining the role of p12 CDK2AP1 in neoplastic growth by temporally ablating p12 CDK2AP1 expression specifically in adult head and neck tissues and developing novel tumor-targeted gene therapy strategies for future translational applications. The examination of the cellular and molecular responses to p12 CDK2AP1 ablation and therapy will provide insights into the functions of this cell cycle regulator in normal and neoplastic growth in vivo. This K01 mechanism is critical in assuring the time and resources needed for the development of the candidate into an independent research scientist in the field of cancer biology.
|Zolochevska, Olga; Figueiredo, Marxa L (2010) Novel tumor growth inhibition mechanism by cell cycle regulator cdk2ap1 involves antiangiogenesis modulation. Microvasc Res 80:324-31|
|Zolochevska, Olga; Figueiredo, Marxa L (2009) Expression of cell cycle regulator cdk2ap1 suppresses tumor cell phenotype by non-cell-autonomous mechanisms. Oral Oncol 45:e106-12|
|Figueiredo, Marxa L; Kao, Chinghai; Wu, Lily (2007) Advances in preclinical investigation of prostate cancer gene therapy. Mol Ther 15:1053-64|