The Kern laboratory was the first to accurately document genetic alteration of, localize, and publish sequences of the tumor-suppressor genes BRCA2 and DPC4. The genetic clues from pancreaticobiliary cancers have thus had wide importance for the understanding of other adult-onset cancers. The genetic basis of pancreatic and biliary cancer is among the best-defined of all human cancers. This understanding includes a high proportion of cases, due to various types of inherited cancer susceptibility, and a very high number of molecularly defined genetic alterations per tumor. With the possible exception of colorectal cancer, no other tumor system is known in greater detail. The research is accomplished with a full spectrum of approaches, from the clinical interests of the world’s most active pancreatic cancer center to the application of cutting-edge basic science in an interdepartmental approach.
The laboratory is developing screening tests and therapeutic models to identify promising small drug therapies for the common adult-onset cancers based on our understanding of TGF-beta, p53, and DNA-repair functions in cancer cells. Signaling pathways of key tumor-suppressors are defined in order to suggest rational therapeutic approaches. There are simultaneous efforts to characterize clinical markers of neoplasia that would allow detection at the curable, pre-invasive stages.
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- Brody, J. R., T. Hucl, C. L. Costantino, J. R. Eshleman, E. Gallmeier, H. Zhu, M. S. van der Heijden, J. M. Winter, A. K. Wikiewicz, C. J. Yeo, and S. E. Kern. 2009. Limits to thymidylate synthase and TP53 genes as predictive determinants for fluoropyrimidine sensitivity and further evidence for RNA-based toxicity as a major influence. Cancer Res 69:984-91.
- Singhal, H.; Ren, Y.R.; Kern, S.E. Improved DNA electrophoresis in conditions favoring polyborates and lewis acid complexation. PLoS One. 2010;5(6):e11318.
- Cao, D., R. Ashfaq, M. G. Goggins, R. H. Hruban, S. E. Kern, and C. A. Iacobuzio-Donahue. 2008. Differential Expression of Multiple Genes in Association with MADH4/DPC4/SMAD4 Inactivation in Pancreatic Cancer. Int J Clin Exp Pathol 1:510-7.
- Jones, S., X. Zhang, D. W. Parsons, J. C. Lin, R. J. Leary, P. Angenendt, P. Mankoo, H. Carter, H. Kamiyama, A. Jimeno, S. M. Hong, B. Fu, M. T. Lin, E. S. Calhoun, M. Kamiyama, K. Walter, T. Nikolskaya, Y. Nikolsky, J. Hartigan, D. R. Smith, M. Hidalgo, S. D. Leach, A. P. Klein, E. M. Jaffee, M. Goggins, A. Maitra, C. Iacobuzio-Donahue, J. R. Eshleman, S. E. Kern, R. H. Hruban, R. Karchin, N. Papadopoulos, G. Parmigiani, B. Vogelstein, V. E. Velculescu, and K. W. Kinzler. 2008. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321:1801-6.
- Swanson, K. D., J. M. Winter, M. Reis, M. Bentires-Alj, H. Greulich, R. Grewal, R. H. Hruban, C. J. Yeo, Y. Yassin, O. Iartchouk, K. Montgomery, S. P. Whitman, M. A. Caligiuri, M. L. Loh, D. G. Gilliland, A. T. Look, R. Kucherlapati, S. E. Kern, M. Meyerson, and B. G. Neel. 2008. SOS1 mutations are rare in human malignancies: implications for Noonan Syndrome patients. Genes Chromosomes Cancer 47:253-9.
- Winter, J. M., A. H. Ting, F. Vilardell, E. Gallmeier, S. B. Baylin, R. H. Hruban, S. E. Kern, and C. A. Iacobuzio-Donahue. 2008. Absence of E-cadherin expression distinguishes noncohesive from cohesive pancreatic cancer. Clin Cancer Res 14:412-8.
- Jones, S.; Zhang, X.; Parsons, D.W.; Lin, J.C.; Leary, R.J.; Angenendt, P.; Mankoo, P.; Carter, H.; Kamiyama, H.; Jimeno, A.; Hong, S.M.; Fu, B.; Lin, M.T.; Calhoun, E.S.; Kamiyama, M.; Walter, K.; Nikolskaya, T.; Nikolsky, Y.; Hartigan, J.; Smith, D.R.; Hidalgo, M.; Leach, S.D.; Klein, A.P.; Jaffee, E.M.; Goggins, M.; Maitra, A.; Iacobuzio-Donahue, C.; Eshleman, J.R.; Kern, S.E.; Hruban, R.H.; Karchin, R.; Papadopoulos, N.; Parmigiani, G.; Vogelstein, B.; Velculescu, V.E.; Kinzler, K.W. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008 Sep 26;321(5897):1801-1806.
- Winter, J.M.; Ting, A.H.; Vilardell, F.; Gallmeier, E.; Baylin, S.B.; Hruban, R.H.; Kern, S.E.; Iacobuzio-Donahue, C.A. Absence of E-cadherin expression distinguishes noncohesive from cohesive pancreatic cancer. Clin Cancer Res. 2008 Jan 15;14(2):412-418.
- Minneci, P. C., K. J. Deans, B. Hansen, C. Parent, C. Romines, D. A. Gonzales, S. X. Ying, P. Munson, A. F. Suffredini, J. Feng, M. A. Solomon, S. M. Banks, S. J. Kern, R. L. Danner, P. Q. Eichacker, C. Natanson, and S. B. Solomon. 2007. A canine model of septic shock: balancing animal welfare and scientific relevance. Am J Physiol Heart Circ Physiol 293:H2487-500.
- Kim, K. M., B. M. Choi, S. W. Park, S. H. Lee, L. V. Christensen, J. Zhou, B. H. Yoo, H. W. Shin, K. S. Bae, S. E. Kern, S. H. Kang, and G. J. Noh. 2007. Pharmacokinetics and pharmacodynamics of propofol microemulsion and lipid emulsion after an intravenous bolus and variable rate infusion. Anesthesiology 106:924-34.