This proposal represents the second competing renewal of Vanderbilt's GI SPORE. This SPORE continues to focus on colorectal cancer, the second leading cause of cancer deaths in the US, where it affects more men and women than all other gastrointestinal malignancies combined. Over the last four years, Vanderbilt's GI SPORE has made discoveries and advances that hold great promise toward improvement of the management of individuals with colorectal neoplasia. These include 1) discovery of a novel Wnt antagonist (pyrvinium) and its target (casein kinase 1alpha ) , 2) discovery of a biologically-based, prognostic gene signature for colorectal cancer, 3) evidence that p120 acts as a tumor suppressor in colorectal cancer, 4) development, biological validation and clinical implementation of novel molecular imaging modalities to predict early response to treatment and 5) further development of a unique biorepository of colorectal adenomas, as well as matched normal rectal mucosa and bodily fluids (serum and urine). Our potential for continued success is high based on 1) productivity during the past funding cycles, 2) strong and highly integrative institutional support, 3) recruitment of talented investigators to the field of GI cancer through career development and pilot project funding, 4) access to unparalleled resources for proteomics, drug discovery and small animal imaging, 5) a team of highly interactive clinical investigators and basic scientists working together in a collegial environment and 6) strong Inter-SPORE, pharmaceutical, national and international collaborations. After a rigorous internal and external review process followed by consultation with NCI SPORE administrators, we propose three new projects and continuation of one project. Project 1. Multimodal Imaging &Targeted Therapeutics of Stem Cell-Derived Colon Cancer Project 2. Targeting K-RAS in Colorectal Cancer Project 3. Molecular Markers of Colorectal Cancer Recurrence Project 4. Genetic &Epigenetic Markers of Colorectal Adenoma Recurrence Core A. Administrative Core B. Translational Pathology &Imaging Core C. Biostatistics &Bioinformatics Career Development Program Developmental Research Program

Public Health Relevance

These four projects will transform how we diagnose and treat individuals with colorectal cancer and deepen our understanding of the pathobiology of colorectal neoplasia. A patient advocate is an integral member of each project to help ensure that our translational goals are being met.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-RPRB-M (M1))
Program Officer
Agarwal, Rajeev K
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Vanderbilt University Medical Center
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Zhu, Shoumin; Soutto, Mohammed; Chen, Zheng et al. (2016) Helicobacter pylori-induced cell death is counteracted by NF-κB-mediated transcription of DARPP-32. Gut :
Parang, B; Bradley, A M; Mittal, M K et al. (2016) Myeloid translocation genes differentially regulate colorectal cancer programs. Oncogene 35:6341-6349
Hong, Jun; Chen, Zheng; Peng, Dunfa et al. (2016) APE1-mediated DNA damage repair provides survival advantage for esophageal adenocarcinoma cells in response to acidic bile salts. Oncotarget 7:16688-702
McKenzie, Andrew J; Hoshino, Daisuke; Hong, Nan Hyung et al. (2016) KRAS-MEK Signaling Controls Ago2 Sorting into Exosomes. Cell Rep 15:978-87
Hardbower, Dana M; Singh, Kshipra; Asim, Mohammad et al. (2016) EGFR regulates macrophage activation and function in bacterial infection. J Clin Invest 126:3296-312
Zhao, Yue; Liu, Qi; Acharya, Pankaj et al. (2016) High-Resolution Mapping of RNA Polymerases Identifies Mechanisms of Sensitivity and Resistance to BET Inhibitors in t(8;21) AML. Cell Rep 16:2003-16
Yu, Huapeng H; Dohn, Michael R; Markham, Nicholas O et al. (2016) p120-catenin controls contractility along the vertical axis of epithelial lateral membranes. J Cell Sci 129:80-94
Schulte, Michael L; Khodadadi, Alexandra B; Cuthbertson, Madison L et al. (2016) 2-Amino-4-bis(aryloxybenzyl)aminobutanoic acids: A novel scaffold for inhibition of ASCT2-mediated glutamine transport. Bioorg Med Chem Lett 26:1044-7
Sievers, Chelsie K; Leystra, Alyssa A; Clipson, Linda et al. (2016) Understanding Intratumoral Heterogeneity: Lessons from the Analysis of At-Risk Tissue and Premalignant Lesions in the Colon. Cancer Prev Res (Phila) 9:638-41
Harris, Kelly L; Pulliam, Stephanie R; Okoro, Emmanuel et al. (2016) Western diet enhances benzo(a)pyrene-induced colon tumorigenesis in a polyposis in rat coli (PIRC) rat model of colon cancer. Oncotarget 7:28947-60

Showing the most recent 10 out of 385 publications