//
Skip Navigation
 
 
 
 
 
Print This Page
Share this page: More
 

Dr. Scott Kern

M.D.
Scott Kern
Interests

Genetic Alterations in Pancreatic Cancer

Titles

Professor of Oncology
Professor of Pathology
Co-Director of the Gastronintestinal Cancer Program

Schools\Degrees

M.D., University of Michigan School of Medicine, Ann Arbor, MI

Training

Resident in Medicine, Univeristy of Michigan School of Medicine, Ann Arbor
Fellow in Pathology, Oncology, Gastrointestinal Pathology, Johns Hopkins University School of Medicine

Certifications

American Board of Pathology AP/CP

Clinical Interests

Genetic Oncology of Pancreatic Cancer

Research Summary

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.

 

EM 5/06
 

Journal Citations

Brody, J. R., E. Gallmeier, K. Yoshimura, T. Hucl, P. Kulesza, M. I. Canto, R. H. Hruban, R. D. Schulick, and S. E. Kern. 2006. A proposed clinical test for monitoring fluoropyrimidine therapy: detection and stability of thymidylate synthase ternary complexes. Cancer Biol Ther 5:923-7.

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.

Brody, J. R., T. Hucl, E. Gallmeier, J. M. Winter, S. E. Kern, and K. M. Murphy. 2006. Genomic Copy Number Changes Affecting the Thymidylate Synthase (TYMS) Gene in Cancer: A Model for Patient Classification to Aid Fluoropyrimidine Therapy. Cancer Res 66:9369-73.

Brune, K., T. Abe, M. Canto, L. O'Malley, A. P. Klein, A. Maitra, N. Volkan Adsay, E. K. Fishman, J. L. Cameron, C. J. Yeo, S. E. Kern, M. Goggins, and R. H. Hruban. 2006. Multifocal neoplastic precursor lesions associated with lobular atrophy of the pancreas in patients having a strong family history of pancreatic cancer. Am J Surg Pathol 30:1067-76.

Calhoun, E. S., T. Hucl, E. Gallmeier, K. M. West, D. E. Arking, A. Maitra, C. A. Iacobuzio-Donahue, A. Chakravarti, R. H. Hruban, and S. E. Kern. 2006. Identifying Allelic Loss and Homozygous Deletions in Pancreatic Cancer without Matched Normals Using High-Density Single-Nucleotide Polymorphism Arrays. Cancer Res 66:7920-7928.

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.

Cunningham, S. C., E. Gallmeier, T. Hucl, D. A. Dezentje, E. S. Calhoun, G. Falco, K. Abdelmohsen, M. Gorospe, and S. E. Kern. 2006. Targeted deletion of MKK4 in cancer cells: a detrimental phenotype manifests as decreased experimental metastasis and suggests a counterweight to the evolution of tumor-suppressor loss. Cancer Res 66:5560-4.

Cunningham, S. C., F. Kamangar, M. P. Kim, S. Hammoud, R. Haque, C. Iacobuzio-Donahue, R. Ashfaq, S. E. Kern, A. Maitra, R. E. Heitmiller, M. A. Choti, K. D. Lillemoe, J. L. Cameron, C. J. Yeo, E. Montgomery, and R. D. Schulick. 2006. MKK4 status predicts survival after resection of gastric adenocarcinoma. Arch Surg 141:1095-9; discussion 1100.

Cunningham, S. C., B. McNear, R. S. Pearlman, and S. E. Kern. 2006. Beverage-agarose gel electrophoresis: an inquiry-based laboratory exercise with virtual adaptation. CBE Life Sci Educ 5:281-6.

Foss, C. A., J. J. Fox, G. Feldmann, A. Maitra, C. Iacobuzio-Donohue, S. E. Kern, R. Hruban, and M. G. Pomper. 2007. Radiolabeled anti-claudin 4 and anti-prostate stem cell antigen: initial imaging in experimental models of pancreatic cancer. Mol Imaging 6:131-9.

Gallmeier, E., T. Hucl, E. S. Calhoun, S. C. Cunningham, F. Bunz, J. R. Brody, and S. E. Kern. 2007. Gene-specific selection against experimental fanconi anemia gene inactivation in human cancer. Cancer Biol Ther 6:654-60.

Gallmeier, E., and S. E. Kern. 2007. Targeting Fanconi anemia/BRCA2 pathway defects in cancer: the significance of preclinical pharmacogenomic models. Clin Cancer Res 13:4-10.

Hruban, R. H., M. I. Canto, C. Griffin, S. E. Kern, A. P. Klein, D. Laheru, and C. J. Yeo. 2005. Treatment of familial pancreatic cancer and its precursors. Curr Treat Options Gastroenterol 8:365-75.

Hruban, R. H., A. Maitra, S. E. Kern, and M. Goggins. 2007. Precursors to pancreatic cancer. Gastroenterol Clin North Am 36:831-49, vi.

Hruban, R. H., K. Takaori, M. Canto, E. K. Fishman, K. Campbell, K. Brune, S. E. Kern, and M. Goggins. 2007. Clinical importance of precursor lesions in the pancreas. J Hepatobiliary Pancreat Surg 14:255-63.

Hucl, T., J. R. Brody, E. Gallmeier, C. A. Iacobuzio-Donahue, I. K. Farrance, and S. E. Kern. 2007. High cancer-specific expression of mesothelin (MSLN) is attributable to an upstream enhancer containing a transcription enhancer factor dependent MCAT motif. Cancer Res 67:9055-65.

Hucl, T., E. Gallmeier, and S. E. Kern. 2007. Distinguishing rational from irrational applications of pharmacogenetic synergies from the bench to clinical trials. Cell Cycle 6:1336-41.

Hustinx, S. R., R. H. Hruban, L. M. Leoni, C. Iacobuzio-Donahue, J. L. Cameron, C. J. Yeo, P. N. Brown, P. Argani, R. Ashfaq, N. Fukushima, M. Goggins, S. E. Kern, and A. Maitra. 2005. Homozygous deletion of the MTAP gene in invasive adenocarcinoma of the pancreas and in periampullary cancer: a potential new target for therapy. Cancer Biol Ther 4:83-6.

Hustinx, S. R., L. M. Leoni, C. J. Yeo, P. N. Brown, M. Goggins, S. E. Kern, R. H. Hruban, and A. Maitra. 2005. Concordant loss of MTAP and p16/CDKN2A expression in pancreatic intraepithelial neoplasia: evidence of homozygous deletion in a noninvasive precursor lesion. Mod Pathol 18:959-63.

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.

Kakar, M., J. R. Davis, S. E. Kern, and C. S. Lim. 2007. Optimizing the protein switch: altering nuclear import and export signals, and ligand binding domain. J Control Release 120:220-32.

Kern, S., D. Riester, C. Hildmann, A. Schwienhorst, and F. J. Meyer-Almes. 2007. Inhibitor-mediated stabilization of the conformational structure of a histone deacetylase-like amidohydrolase. Febs J 274:3578-88.

Kern, S. E., and D. Shibata. 2007. The fuzzy math of solid tumor stem cells: a perspective. Cancer Res 67:8985-8.

Kern, S. E., and J. M. Winter. 2006. Elegance, silence and nonsense in the mutations literature for solid tumors. Cancer Biol Ther 5:349-59.

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.

Martin, S. T., H. Matsubayashi, C. D. Rogers, J. Philips, F. J. Couch, K. Brune, C. J. Yeo, S. E. Kern, R. H. Hruban, and M. Goggins. 2005. Increased prevalence of the BRCA2 polymorphic stop codon K3326X among individuals with familial pancreatic cancer. Oncogene 24:3652-6.

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.

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.

van der Heijden, M. S., J. R. Brody, D. A. Dezentje, E. Gallmeier, S. C. Cunningham, M. J. Swartz, A. M. DeMarzo, G. J. Offerhaus, W. H. Isacoff, R. H. Hruban, and S. E. Kern. 2005. In vivo therapeutic responses contingent on Fanconi anemia/BRCA2 status of the tumor. Clin Cancer Res 11:7508-15.

Van der Heijden, M. S., J. R. Brody, E. Elghalbzouri-Maghrani, M. Z. Zdzienicka, and S. E. Kern. 2006. Does tumorigenesis select for or against mutations of the DNA repair-associated genes BRCA2 and MRE11?: Considerations from somatic mutations in microsatellite unstable (MSI) gastrointestinal cancers. BMC Genet 7:3.

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.

Wood, L. D., E. S. Calhoun, N. Silliman, J. Ptak, S. Szabo, S. M. Powell, G. J. Riggins, T. L. Wang, H. Yan, A. Gazdar, S. E. Kern, L. Pennacchio, K. W. Kinzler, B. Vogelstein, and V. E. Velculescu. 2006. Somatic mutations of GUCY2F, EPHA3, and NTRK3 in human cancers. Hum Mutat 27:1060-1.

Brody, J. R., Calhoun, E. S., Gallmeier, E., & Kern, S. E. 2004.Ultra-fast, high-resolution agarose electrophoresis of DNA and RNA using low-molarity conductive media. BioTechniques. 37:598-602.

Gallmeier E., Winter J. M., Cunningham, S. C., Kahn, S. R., & Kern, S. E. 2005.Novel genotoxicity assays identify norethindrone to activate p53 and to phosphorylate H2AX. Carcinogenesis 26:1811-1820.

Van der Heijden, M. S., Brody, J. R., Dezentje, D. A., Gallmeier, E., Swartz, M. J., Demarzo, A. M., Offerhaus, J. H., Isacoff, W. H., Hruban, R. H., & Kern S. E. 2005. In vivo therapeutic responses contingent upon Fanconi anemia/BRCA2 status of the tumor. Clin. Cancer Res. 11:7508-7515.

Van der Heijden, M. S., Brody, . JR., Gallmeie, E., Cunningham, S. C., Dejentje, D. A., Shen, D., Hruban, R. H., Kern, S. E. 2004. Functional defects in the Fanconi anemia pathway in cancer cells. Amer. J. Pathol. 165:651-657.

Wood, L.D.; Calhoun, E.S.; Silliman, N.; Ptak, J.; Szabo, S.; Powell, S.M.; Riggins, G.J.; Wang, T.L.; Yan, H.; Gazdar, A.; Kern, S.E.; Pennacchio, L.; Kinzler, K.W.; Vogelstein, B.; Velculescu, V.E. Somatic mutations of GUCY2F, EPHA3, and NTRK3 in human cancers. Hum Mutat. 2006 Oct;27(10):1060-1061.

Foss, C.A.; Fox, J.J.; Feldmann, G.; Maitra, A.; Iacobuzio-Donohue, C.; Kern, S.E.; Hruban, R.; Pomper, M.G. Radiolabeled anti-claudin 4 and anti-prostate stem cell antigen: initial imaging in experimental models of pancreatic cancer. Mol Imaging. 2007 Mar-Apr;6(2):131-139.

Gallmeier, E.; Hucl, T.; Calhoun, E.S.; Cunningham, S.C.; Bunz, F.; Brody, J.R.; Kern, S.E. Gene-specific selection against experimental fanconi anemia gene inactivation in human cancer. Cancer Biol Ther. 2007 May;6(5):654-660.

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.

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.

 

Read Our Blogs
Cancer Matters: timely topics
Our Cancer: for caregivers

Traveling for care?

blue suitcase

Whether crossing the country or the globe, we make it easy to access world-class care at Johns Hopkins.

Maryland 410-955-5222
U.S. 410-955-5222
International +1-410-614-6424

NCI CCC

 
 
 
 
 

© The Johns Hopkins University, The Johns Hopkins Hospital, and Johns Hopkins Health System. All rights reserved.