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D'Cunha_J

Research Abstracts Online
January 2009 - March 2010

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University of Minnesota Twin Cities
Medical School
Department of Surgery

PI: Jonathan D'Cunha

Translational Control of Lung Cancer: Mechanistic Studies in Tumorigenesis

Lung cancer is a leading cause of cancer-related deaths in the United States (US) and worldwide. Therefore, developing new molecular targets for lung cancer therapy remains a top priority. Non-small cell lung cancer (NSCLC) comprises 80% of all lung cancers. A growing body of evidence clearly indicates that enhanced translation is a characteristic of malignant transformation in a number of tumors, including NSCLC. Even with best standard medical and surgical therapy, the outlook for patients is often dismal upon diagnosis. Thus, molecular controls of this pathway are attractive targets for novel therapies. To this end, these researchers are very interested in the molecular events following translational activation that lead to the development of NSCLC. In-depth understanding of this will potentially lead to new therapeutic approaches.

Previous work from this laboratory has demonstrated that repression of enhanced translational activity in NSCLC results in reversion of the malignant phenotype in vitro and in vivo. Based on this previous work and accumulating work by others in translational control, the researchers hypothesize that enhanced translational activation is a key event in tumorigenesis in NSCLC. To better understand the important malignancy-associated proteins regulated by enhanced translational activity, they are investigating the molecular mechanisms of translational activation in NSCLC by activating the translational control complex of human bronchial epithelial cells thereby rendering them tumorigenic. The tumorigenic clones will be analyzed at the molecular level in vitro and in vivo. The researchers will then seek to identify the key transcripts accounting for oncogenesis. Finally, they will test small molecule inhibitors of key proteins that account for tumorigenesis as a potential novel therapeutic strategy. These investigations will then serve as a backbone for future investigations into a much-needed new class of therapeutics for NSCLC.

Group Members

Joel McCauley, Graduate Student
Scott Selby, Research Associate