M.D., Ph.D., Johns Hopkins University,1994
Pancreatic cancer, experimental therapeutics, diagnostics, mouse models, cancer genetics
phone (516) 367-5246, fax (516) 367-8353
The Tuveson laboratory investigates fundamental aspects of cancer biology and applies this knowledge towards the development of new therapeutic and diagnostic strategies. We focus on Pancreatic ductal adenocarcinoma (PDAC), the most lethal common cancer with a five year survival rate of only 6%. These grim statistics reflect our inability to detect early stage disease, its highly metastatic propensity and therapeutic resistance. Therefore we have developed mouse models of PDAC to discover biomarkers of early disease; to identify the pathways and druggable targets involved in the initiation, progression and metastasis of PDA; and to develop efficacious therapeutic strategies.
We have discovered that PDAC tumors contain a deficient and compressed vasculature that limits therapeutic delivery and therefore efficacy. Using these models we have uncovered several methods to correct or target these vascular deficits and promote response, and this information has led to the initiation of several clinical trials. At CSHL we will search for new vulnerabilities in PDAC neoplastic and microenvironmental cells, and evaluate these candidates in a futuristic “Mouse Hospital” we are creating on campus. Our efforts will include novel therapeutic platforms related to the rich environment of cancer science at CSHL, and bespoke methodologies to develop a new generation of diagnostic approaches for disease detection and tumor monitoring. We aim to translate our preclinical results into the design of pivotal investigational clinical studies.
Dr. Tuveson serves as Director of the Lustgarten Foundation Pancreatic Research Laboratory at CSHL and as Director of Research for the Lustgarten Foundation.
DeNicola, G.M., Karreth, F.A., Humpton, T.J., Gopinathan, A., Wei, C., Frese, K., Mangal, D., Yu, K.H., Yeo, C.J., Calhoun, E.S., Scrimieri, F., Winter, J.M., Hruban, R.H., Iacobuzio-Donahue, C., Kern, S.E., Blair, I.A., and Tuveson, D.A. 2011. Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature. 475: 106–109.
Cook, N., Frese, K.K., Bapiro, T.E., Jacobetz, M.A., Gopinathan, A., Miller, J.L., Rao, S.S., Demuth, T., Howat, W.J., Jodrell, D.I., and Tuveson, D.A. 2012. Gamma secretase inhibition promotes hypoxic necrosis in mouse pancreatic ductal adenocarcinoma. J Exp Med. 209: 437–444.
Frese, K.K., Neesse, A., Cook, N., Bapiro, T., Lolkema, M.P., 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: 260–269.
Jacobetz, M.A., Chan, D.S., Neesse, A., Bapiro, T.E., Cook, N., Frese, K.K., Feig, C., Nakagawa, T., Caldwell, M.E., Zecchini, H.I., Lolkema, M.P., Jiang, P., Kultti, A., Thompson, C.B., Maneval, D.C., Jodrell, D.I., Frost, G.I., Shepard, H.M., Skepper, J.N., and Tuveson, D.A. 2012. Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer. Gut Epub 30 March.
Pérez-Mancera, P.A., Rust, A.G., van der Weyden, L., Kristiansen, G., Li, A., Sarver, A.L., Silverstein, K.A.T, Grützmann, R., Aust, D., Rümmele, P., Knösel, T., Herd, C., Stemple, D.L., Kettleborough, R., Brosnan, J.A., Li, A., Morgan, R., Knight, S., Yu, J., Stegeman, S., Collier, L.S., ten Hoeve, J.J., de Ridder, J., Klein, A.P., Goggins, M., Hruban, R.H., Chang, D.K., Biankin, A.V., Grimmond, S.M., Australian Pancreatic Cancer Genome Initiative, Wessels, L.F.A., Wood, S.A., Iacobuzio-Donahue, C.A., Pilarsky, C., Largaespada, D.A., Adams, D.J., and Tuveson, D.A. 2012. The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma. Nature 486: 266–270.