The applicant describes a five-year program leading to independent translational research related to gastrointestinal cancer. The goals of this career development program are: 1) to further the ongoing research in biomarker discovery for colorectal cancer, 2) to gain new knowledge and experience with proteomic technology, and 3) to become an independent researcher focused on the development of novel diagnostic and therapeutic modalities for gastrointestinal cancer. Laboratory skills in molecular biology, mouse models, genomics, and proteomics will be fostered in the laboratory of one of the co- mentors, Dr. Raju Kucherlapati. He is an accomplished scientist with vast experience in mouse models of cancer, genomics, and proteomics. The other co-mentor, Dr. Daniel Podolsky, will serve as a clinical and scientific advisor to the project and foster the professional development of the investigator. Colorectal cancer is the third leading cause of cancer-related mortality in the United States. As stated in The Nation's Investment in Cancer Research FY 2006, we will be able """"""""to eliminate the suffering and death due to cancer"""""""" when we are able to """"""""detect many cancers early enough to make successful treatment possible."""""""" Early diagnosis of colorectal cancer by colonoscopy increases the probability of survival. However, this is an invasive screening procedure limited by available endoscopy resources and patient compliance. Clearly, a robust non-invasive assay is necessary. In light of the recent advances in proteomics, the investigator proposes to use mass spectrometry-based methods to identify plasma biomarkers for colorectal cancer. To overcome the inherent variability in human studies, the investigator has focused on mouse models of colon cancer. Preliminary data suggest that one is able to identify plasma proteins that act as surrogate markers for cancer in mice with high tumor burdens. The proposed plan extends the preliminary studies to determine if one can: 1) identify mice with minimal tumor burden, 2) discriminate between mice with tubular and villous adenomas, and 3) identify mice with carcinomas. The research will be conducted in the laboratory of Dr. Raju Kucherlapati. The investigator will have full access to the Harvard Partners Center for Genetics and Genomics Proteomics Facility, as well as other facilities throughout the Harvard Longwood Medical area. It is anticipated that the guidance and training received from this program will allow the investigator to achieve his goal: to be an independent researcher in academic gastrointestinal medicine. Relevance: This proposal will lay the foundation for the identification of biomarkers which may be used for the early detection of colorectal cancer through the analysis of perhaps a single drop of blood.
