Bert Vogelstein, M.D.
Fax: (410) 955-0548
Interests:
- Genetic Alterations of Colon Cancer
Titles
Clayton Professor of Oncology
Investigator of the Howard Hughes Medical Institute
Professor of Oncology
Professor of Pathology
Joint Appointment in Molecular Biology and Genetics
Schools/Degrees
M.D., Johns Hopkins University, Baltimore, MD
Training
Resident in Pediatrics, Johns Hopkins School of MedicineFellow in Pediatrics, Johns Hopkins school of MedicineResearch Associate, Tumor Cell Biology, National Cancer Institute
More about the scientist whose work has influenced cancer revolutionToday Show features "A Day in the Life of a Scientist" March 17, 2005
Vogelstein Wins "Nobel" of Spain: the Prince of Asturias AwardAcademy of Achievement: Uncovering the Genetic Causes of CancerHoward Hughes Medical Institute: Career HighlightsWhen the Sun Goes Down: Bert "Rockin' Doc" Vogelstein Rocks the Town
Vogelstein and Kinzler on the Future of Cancer Research
Clinical Interests
Timeline of Genetic Discoveries
Research Summary
Dr. Vogelstein and his colleagues have demonstrated that human colorectal tumors represent the expansion of a single transformed cell. The initiation of this process is due to mutations in genes controlling the APC/b-catenin pathway. Progress is due to mutations in other genes, such as c-Ki-Ras, p53, and those controlling the responses to TGF-b and related ligands. These mutations occur in a preferred order as the tumor progresses from benign to malignant stages and can occur either through inherited or somatic means. Genetic alterations affecting genetic stability, such as those resulting in mismatch repair defects or aberrant chromosome segregation, can lead to an accelerated accumulation of somatic mutations and predisposition to cancer.
Dr. Vogelstein’s current work is devoted to the use of sophisticated molecular genetic methods to probe the function of the genes noted above in colorectal cancer cells. His group has developed powerful methods to disrupt specific genes in colorectal cancer cells for this purpose. Additionally, they have invented new technologies for detecting mutations and used these technologies to improve early cancer detection and diagnosis of hereditary susceptibility. Other research in his laboratory focuses on the design of novel therapeutic agents targeting the epithelial and non-epithelial components of colorectal cancers.
Journal Citations
Sur, S., Pagliarini, R., Bunz, F., Rago, C., Diaz, L.A. Jr., Kinzler, K.W., Vogelstein, B., and Papadopoulos, N. (2009). A new panel of isogenic human cancer cells suggests a therapeutic approach for cancers with inactivated p53. PNAS. 106, 3964-3969.
Yan, H., Parsons, W., Jin, G., McLendon, R., Rasheed, A.B., Yuan, W., Kos, I., Batinic-Haberle, I., Jones, S., Riggins, G.J., Friedman, H., Friedman, A., Reardon, D., Herndon, J., Kinzler, K.W., Velculescu, V.E., Vogelstein, B., and Bigner, D.D. (2009). IDH1 and IDH2 Mutations in Gliomas. NEJM. 360, 765-773.
Parmigiani, G., Boca, S., Lin, J., Kinzler, K.W., Velculescu, V., and Vogelstein, B. (2009). Design and analysis issues in genome-wide somatic mutation studies of cancer. Genomics 93, 17-21.
Parsons, D.W., Jones, S., Zhang, X., Lin, J.C., Leary, R.J., Angenendt, P., Mankoo, P., Carter, H., Siu, I.M., Gallia, G.L., Olivi, A., McLendon, R., Rasheed, B.A., Keir, S., Nikolskaya, T., Nikolsky, Y., Busam, D.A., Tekleab, H., Diaz, L.A., Jr., Hartigan, J., Smith, D.R., Strausberg, R.L., Marie, S.K., Shinjo, S.M., Yan, H., Riggins, G.J., Bigner, D.D., Karchin, R., Papadopoulos, N., Parmigiani, G., Vogelstein, B., Velculescu, V.E., and Kinzler, K.W. (2008). An integrated genomic analysis of human glioblastoma multiforme. Science 321, 1807-1812.
Wood, L. D., D. W. Parsons, S. Jones, J. Lin, T. Sjoblom, R. J. Leary, D. Shen, S. M. Boca, T. Barber, J. Ptak, N. Silliman, S. Szabo, Z. Dezso, V. Ustyanksky, T. Nikolskaya, Y. Nikolsky, R. Karchin, P. A. Wilson, J. S. Kaminker, Z. Zhang, R. Croshaw, J. Willis, D. Dawson, M. Shipitsin, J. K. Willson, S. Sukumar, K. Polyak, B. H. Park, C. L. Pethiyagoda, P. V. Pant, D. G. Ballinger, A. B. Sparks, J. Hartigan, D. R. Smith, E. Suh, N. Papadopoulos, P. Buckhaults, S. D. Markowitz, G. Parmigiani, K. W. Kinzler, V. E. Velculescu, and B. Vogelstein. 2007. The genomic landscapes of human breast and colorectal cancers. Science 318:1108-13.
Zhang, X., M. Zhao, M. A. Rudek, P. He, and B. Vogelstein. 2007. Development and validation of a liquid chromatography/tandem mass spectrometry method for the determination of DMXAA in human and mouse plasma. J Chromatogr B Analyt Technol Biomed Life Sci 852:217-22.
Amzel, L.M., Huang, C.H., Mandelker, D., Lengauer, C., Gabelli, S.B., and Vogelstein, B. (2008). Structural comparisons of class I phosphoinositide 3-kinases. Nat Rev Cancer 8, 665-669.
Barber, T.D., McManus, K., Yuen, K.W., Reis, M., Parmigiani, G., Shen, D., Barrett, I., Nouhi, Y., Spencer, F., Markowitz, S., Velculescu, V.E., Kinzler, K.W., Vogelstein, B., Lengauer, C., and Hieter, P. (2008). Chromatid cohesion defects may underlie chromosome instability in human colorectal cancers. Proc Natl Acad Sci U S A 105, 3443-3448.
Diehl, F., Schmidt, K., Choti, M.A., Romans, K., Goodman, S., Li, M., Thornton, K., Agrawal, N., Sokoll, L., Szabo, S.A., Kinzler, K.W., Vogelstein, B., and Diaz, L.A., Jr. (2008). Circulating mutant DNA to assess tumor dynamics. Nature medicine 14, 985-990.
Diehl, F., Schmidt, K., Durkee, K.H., Moore, K.J., Goodman, S.N., Shuber, A.P., Kinzler, K.W., and Vogelstein, B. (2008). Analysis of mutations in DNA isolated from plasma and stool of colorectal cancer patients. Gastroenterology 135, 489-498.
He, Y., Vogelstein, B., Velculescu, V.E., Papadopoulos, N., and Kinzler, K.W. (2008). The antisense transcriptomes of human cells. Science 322, 1855-1857.
Jones, S., Chen, W.D., Parmigiani, G., Diehl, F., Beerenwinkel, N., Antal, T., Traulsen, A., Nowak, M.A., Siegel, C., Velculescu, V.E., Kinzler, K.W., Vogelstein, B., Willis, J., and Markowitz, S.D. (2008). Comparative lesion sequencing provides insights into tumor evolution. Proc Natl Acad Sci U S A 105, 4283-4288.
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., and Kinzler, K.W. (2008). Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science (New York, N.Y 321, 1801-1806.
Diaz, L. A., C. A. Foss, K. Thornton, S. Nimmagadda, C. J. Endres, O. Uzuner, T. M. Seyler, S. D. Ulrich, J. Conway, C. Bettegowda, N. Agrawal, I. Cheong, X. Zhang, P. W. Ladenson, B. N. Vogelstein, M. A. Mont, S. Zhou, K. W. Kinzler, B. Vogelstein, and M. G. Pomper. 2007. Imaging of Musculoskeletal Bacterial Infections by [I]FIAU-PET/CT. PLoS ONE 2:e1007.
Huang, C. H., D. Mandelker, O. Schmidt-Kittler, Y. Samuels, V. E. Velculescu, K. W. Kinzler, B. Vogelstein, S. B. Gabelli, and L. M. Amzel. 2007. The structure of a human p110alpha/p85alpha complex elucidates the effects of oncogenic PI3Kalpha mutations. Science 318:1744-8.
Lin, J., C. M. Gan, X. Zhang, S. Jones, T. Sjoblom, L. D. Wood, D. W. Parsons, N. Papadopoulos, K. W. Kinzler, B. Vogelstein, G. Parmigiani, and V. E. Velculescu. 2007. A multidimensional analysis of genes mutated in breast and colorectal cancers. Genome Res 17:1304-18.
Rago, C., B. Vogelstein, and F. Bunz. 2007. Genetic knockouts and knockins in human somatic cells. Nat Protoc 2:2734-46.
Rago, C., D. L. Huso, F. Diehl, B. Karim, G. Liu, N. Papadopoulos, Y. Samuels, V. E. Velculescu, B. Vogelstein, K. W. Kinzler, and L. A. Diaz, Jr. 2007. Serial assessment of human tumor burdens in mice by the analysis of circulating DNA. Cancer Res 67:9364-70.
Bachman, K. E., Sager, J., Cheong, I., Catto, M., Bardelli, A., Park, B. H., Vogelstein, B., Carotti, A., Kinzler, K. W. & Lengauer, C. (2005). Identification of compounds that inhibit growth of 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine-resistant cancer cells. Mol Cancer Ther 4, 1026-30.
Bettegowda, C., Foss, C. A., Cheong, I., Wang, Y., Diaz, L., Agrawal, N., Fox, J., Dick, J., Dang, L. H., Zhou, S., Kinzler, K. W., Vogelstein, B. & Pomper, M. G. (2005). Imaging bacterial infections with radiolabeled 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodouracil. Proc Natl Acad Sci U S A 102, 1145-50.
Bettegowda, C., Huang, X., Lin, J., Cheong, I., Kohli, M., Szabo, S. A., Zhang, X., Diaz, L. A., Jr., Velculescu, V. E., Parmigiani, G., Kinzler, K. W., Vogelstein, B. & Zhou, S. (2006). The genome and transcriptomes of the anti-tumor agent Clostridium novyi-NT. Nat Biotechnol.
Cheong, I., Huang, X., Bettegowda, C., Diaz, L. A., Jr., Kinzler, K. W., Zhou, S. & Vogelstein, B. (2006). A bacterial protein enhances the release and efficacy of liposomal cancer drugs. Science 314, 1308-11.
Cummins, J. M., He, Y., Leary, R. J., Pagliarini, R., Diaz, L. A., Jr., Sjoblom, T., Barad, O., Bentwich, Z., Szafranska, A. E., Labourier, E., Raymond, C. K., Roberts, B. S., Juhl, H., Kinzler, K. W., Vogelstein, B. & Velculescu, V. E. (2006). The colorectal microRNAome. Proc Natl Acad Sci U S A 103, 3687-92.
Diehl, F., Li, M., Dressman, D., He, Y., Shen, D., Szabo, S., Diaz, L. A., Jr., Goodman, S. N., David, K. A., Juhl, H., Kinzler, K. W. & Vogelstein, B. (2005). Detection and quantification of mutations in the plasma of patients with colorectal tumors. Proc Natl Acad Sci U S A 102, 16368-73.
Diehl, F., Li, M., He, Y., Kinzler, K. W., Vogelstein, B. & Dressman, D. (2006). BEAMing: single-molecule PCR on microparticles in water-in-oil emulsions. Nat Methods 3, 551-9.
Li, M., Diehl, F., Dressman, D., Vogelstein, B. & Kinzler, K. W. (2006). BEAMing up for detection and quantification of rare sequence variants. Nat Methods 3, 95-7.
Nanda, A., Karim, B., Peng, Z., Liu, G., Qiu, W., Gan, C., Vogelstein, B., St Croix, B., Kinzler, K. W. & Huso, D. L. (2006). Tumor endothelial marker 1 (Tem1) functions in the growth and progression of abdominal tumors. Proc Natl Acad Sci U S A 103, 3351-6.
Papadopoulos, N., Kinzler, K. W. & Vogelstein, B. (2006). The role of companion diagnostics in the development and use of mutation-targeted cancer therapies. Nat Biotechnol 24, 985-95.
Parsons, D. W., Wang, T. L., Samuels, Y., Bardelli, A., Cummins, J. M., DeLong, L., Silliman, N., Ptak, J., Szabo, S., Willson, J. K., Markowitz, S., Kinzler, K. W., Vogelstein, B., Lengauer, C. & Velculescu, V. E. (2005). Colorectal cancer: mutations in a signalling pathway. Nature 436, 792.
Peters, B. A., Diaz, L. A., Polyak, K., Meszler, L., Romans, K., Guinan, E. C., Antin, J. H., Myerson, D., Hamilton, S. R., Vogelstein, B., Kinzler, K. W. & Lengauer, C. (2005). Contribution of bone marrow-derived endothelial cells to human tumor vasculature. Nat Med 11, 261-2.
Samuels, Y., Diaz, L. A., Jr., Schmidt-Kittler, O., Cummins, J. M., Delong, L., Cheong, I., Rago, C., Huso, D. L., Lengauer, C., Kinzler, K. W., Vogelstein, B. & Velculescu, V. E. (2005). Mutant PIK3CA promotes cell growth and invasion of human cancer cells. Cancer Cell 7, 561-73.
Sjoblom, T., Jones, S., Wood, L. D., Parsons, D. W., Lin, J., Barber, T. D., Mandelker, D., Leary, R. J., Ptak, J., Silliman, N., Szabo, S., Buckhaults, P., Farrell, C., Meeh, P., Markowitz, S. D., Willis, J., Dawson, D., Willson, J. K., Gazdar, A. F., Hartigan, J., Wu, L., Liu, C., Parmigiani, G., Park, B. H., Bachman, K. E., Papadopoulos, N., Vogelstein, B., Kinzler, K. W. & Velculescu, V. E. (2006). The consensus coding sequences of human breast and colorectal cancers. Science 314, 268-74.
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. (2006). Somatic mutations of GUCY2F, EPHA3, and NTRK3 in human cancers. Hum Mutat 27, 1060-1.
Baker, S. J., Kinzler, K. W., & Vogelstein, B. 2003. Knudson’s hypothesis and the TP53 revolution. Gene. Chromosome. Canc. 38:329.
Bardelli, A., Saha, S., Sager, J. A., Romans, K. E., Xin, B., Markowitz, S. D., et al. 2003. PRL-3 Expression in metastatic cancer. Clin. Cancer Res. 9:5607-5615.
Bettegowda, C., Dang, L. H., Abrams, R., Huso, D. L., Dillehay, L., Cheong, I., et al. 2003. Overcoming the hypoxic barrier to radiation therapy with anaerobic bacteria. Proc. Natl. Acad. Sci. USA. 100:15083-15088.
Dressman, D., Yan, H., Traverso, G., Kinzler, K. W., & Vogelstein, B. 2003. Transforming single DNA molecules into fluorescent magnetic particles for detection and enumeration of genetic variations. Proc. Natl. Acad. Sci. USA. 100:8817-8822.
Traverso, G., Bettegowda, C., Kraus, J., Speicher, M. R., Kinzler, K. W., Vogelstein, B., et al. 2003. Hyper-recombination and genetic instability in BLM-deficient epithelial cells. Cancer Res. 63:8578-8581.
Wang, Z., Vogelstein, B., & Kinzler, K. W. 2003. Phosphorylation of beta-catenin at S33, S37, or T41 can occur in the absence of phosphorylation at T45 in colon cancer cells. Cancer Res. 63:5234-5235.
