Pancreatic cancer is an extremely lethal malignancy. On average, patients who are diagnosed with pancreatic cancer succumb to the disease within 6 months. Research is the only way to defeat pancreatic cancer. My lab is making progress toward finding a cure by detecting the disease earlier and designing novel therapeutic approaches.
David Tuveson’s laboratory uses murine and human models of pancreatic cancer to explore the fundamental biology of malignancy and thereby identify new diagnostic and treatment strategies. The lab’s approaches run the gamut from designing new model systems of disease to developing new therapeutic and diagnostic approaches for rapid evaluation in preclinical and clinical settings. The lab’s studies make use of organoid cultures—three-dimensional cultures of normal or cancerous epithelia—as ex vivo models to probe cancer biology. Current projects in the lab explore changes in redox metabolism associated with pancreatic cancer tumorigenesis, dissect signaling by the Ras oncogene, discover new biomarkers of early pancreas cancer, and identify mechanisms of cross-talk between pancreatic cancer cells and the tumor stroma. Novel treatment approaches suggested by these studies are then tested by performing therapeutic experiments in mouse models. To dissect molecular changes associated with pancreatic tumorigenesis, the Tuveson lab has generated a large collection of human patient-derived organoid models. By measuring the therapeutic sensitivities of patient-derived organoids, the lab is working to identify novel strategies to treat patients as well as markers of therapeutic response. The Tuveson Laboratory maintains strong links to clinical research, and the ultimate goal is confirmation of preclinical findings in early-phase trials. Collectively, the lab’s bench-to-bedside approach is codified as the “Cancer Therapeutics Initiative,” and this initiative will provide these same approaches to the entire CSHL cancer community.
Dr. Tuveson serves as Director of the Cold Spring Harbor Laboratory Cancer Center and the Chief Scientist for the Lustgarten Foundation.
Jacobetz, M. A. and Chan, D. S. and Neesse, A. and Bapiro, T. E. and Cook, N. and Frese, K. K. and Feig, C. and Nakagawa, T. and Caldwell, M. E. and Zecchini, H. I. and Lolkema, M. P. and Jiang, P. and Kultti, A. and Thompson, C. B. and Maneval, D. C. and Jodrell, D. I. and Frost, G. I. and Shepard, H. M. and Skepper, J. N. and Tuveson, D. A. (2013) Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer. Gut, 62(1) pp. 112-20.
Perez-Mancera, P. A. and Rust, A. G. and van der Weyden, L. and Kristiansen, G. and Li, A. and Sarver, A. L. and Silverstein, K. A. and Grutzmann, R. and Aust, D. and Rummele, P. and Knosel, T. and Herd, C. and Stemple, D. L. and Kettleborough, R. and Brosnan, J. A. and Li, A. and Morgan, R. and Knight, S. and Yu, J. and Stegeman, S. and Collier, L. S. and ten Hoeve, J. J. and de Ridder, J. and Klein, A. P. and Goggins, M. and Hruban, R. H. and Chang, D. K. and Biankin, A. V. and Grimmond, S. M. and Wessels, L. F. and Wood, S. A. and Iacobuzio-Donahue, C. A. and Pilarsky, C. and Largaespada, D. A. and Adams, D. J. and Tuveson, D. A. (2012) The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma. Nature, 486(7402) pp. 266-70.
Cook, N. and Frese, K. K. and Bapiro, T. E. and Jacobetz, M. A. and Gopinathan, A. and Miller, J. L. and Rao, S. S. and Demuth, T. and Howat, W. J. and Jodrell, D. I. and Tuveson, D. A. (2012) Gamma secretase inhibition promotes hypoxic necrosis in mouse pancreatic ductal adenocarcinoma. J Exp Med, 209(3) pp. 437-44.
Frese, K. K. and Neesse, A. and Cook, N. and Bapiro, T. E. and Lolkema, M. P. and Jodrell, D. I. and Tuveson, D. A. (2012) nab-Paclitaxel potentiates gemcitabine activity by reducing cytidine deaminase levels in a mouse model of pancreatic cancer. Cancer Discov, 2(3) pp. 260-9.
DeNicola, G. M. and Karreth, F. A. and Humpton, T. J. and Gopinathan, A. and Wei, C. and Frese, K. and Mangal, D. and Yu, K. H. and Yeo, C. J. and Calhoun, E. S. and Scrimieri, F. and Winter, J. M. and Hruban, R. H. and Iacobuzio-Donahue, C. and Kern, S. E. and Blair, I. A. and Tuveson, D. A. (2011) Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature, 475(7354) pp. 106-9.Additional materials of the author at
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