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Bert Vogelstein, M.D.

Photo of Dr. Bert Vogelstein, M.D.

Professor of Oncology

Research Interests: Cancer genetics and its clinical implications

Background

Bert Vogelstein, M.D., was the first scientist to elucidate the molecular basis of a common human cancer. In particular, he and his colleagues have demonstrated that colorectal tumors result from the gradual accumulation of genetic alterations in specific oncogenes and tumor suppressor genes. His group’s discovery and analysis of these genes and their functions represent a landmark in the application of molecular biology to the study of human disease. His work on colorectal cancers forms the paradigm for much of modern cancer research, with profound implications for diagnostic and therapeutic strategies in the future. 

Vogelstein’s studies have elucidated the following principles governing the pathogenesis of human neoplasia. First, human tumors represent the expansion of a single transformed cell. Second, the initiation of this process and the expansion of the transformed cell are due to mutations in specific oncogenes and tumor suppressor genes. Third, these mutations occur in a preferred order as the tumor progresses from benign to malignant stages. Fourth, mutations in the same genes can occur either through inherited or somatic pathways. Fifth, naturally occurring mutations in these genes can provide critical clues to their biochemical and physiologic functions. Sixth, heritable alterations affecting genetic stability can lead to an accelerated accumulation of somatic mutations and an associated predisposition to cancer. Finally, knowledge of the genetic alterations responsible for cancer can be used to develop innovative approaches to improve the management of patients with neoplastic disease. 

More recently, Vogelstein and his colleagues were the first to map cancer genomes and use personalized genomic sequencing to identify the genetic culprit to a hereditary cancer. 

Vogelstein attended the University of Pennsylvania, where he graduated summa cum laude with distinction in mathematics and won the Rosenbaum Award for outstanding undergraduate work in Semitic languages and literature. He obtained his medical degree at the Johns Hopkins University School of Medicine and performed his internship and residency in pediatrics at The Johns Hopkins Hospital. Following his clinical training, Vogelstein completed a postdoctoral fellowship at the National Cancer Institute, focusing on new techniques in molecular biology. He returned to Johns Hopkins as an assistant professor of oncology. He is now the Clayton Professor of Oncology and Co-Director of the Ludwig Center at the Johns Hopkins Kimmel Cancer Center. Vogelstein also holds a joint appointment in molecular biology and genetics at The Johns Hopkins University and is a Howard Hughes Medical Institute investigator.

Vogelstein has won numerous awards for his pioneering studies on the pathogenesis of human cancer. These include the Young Investigator Award from the American Federation for Clinical Research, the Bristol-Myers Squibb Award for Distinguished Achievement in Cancer Research, the American Cancer Society Medal of Honor, a Gairdner International Award, the Rabbi Shai Shacknai Memorial Prize from the Hebrew University of Jerusalem, the Dickson Prize in Medicine from the University of Pittsburgh, the Pezcoller Foundation-AACR International Award, the Baxter Award from the Association of American Medical Colleges, the Howard Taylor Ricketts Award from the University of Chicago, the Ernst Schering Prize, the Passano Award, the G.H.A. Clowes Memorial Award from the American Association for Cancer Research, the William Beaumont Prize in Gastroenterology from the American Gastroenterological Association, the David A. Karnofsky Memorial Award from the American Society for Clinical Oncology, the Paul Ehrlich and Ludwig Darmstaedter Prize from the Paul Ehrlich Foundation, the William Allan Award from the American Society of Human Genetics, the Richard Lounsbery Award from the National Academy of Sciences, the Louisa Gross Horwitz Prize from Columbia University, the Harvey Prize in Human Health from the Technion, the Charles S. Mott Prize from the General Motors Cancer Research Foundation, the John Scott Award, the Prince of Asturias Award in Technical and Scientific Research, the Pioneer in Science Award from the American Research Forum, and the Breakthrough Prize in Life Sciences.

Vogelstein was elected to the American Academy of Arts and Sciences and the National Academy of Sciences in 1992, and to the American Philosophical Society in 1995. He became a fellow of the American Association for the Advancement of Science in 2006. His advisory roles have included chairmanship of the National Research Council Committee on the Biological and Biomedical Applications of Stem Cell Research and the Board of Scientific Counselors of the National Human Genome Research Institute. He has also held editorial positions at Science, Molecular Cell, Cancer Cell and The New England Journal of Medicine.

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Titles

  • Professor of Oncology
  • Joint Appointment in Molecular Biology and Genetics
  • Professor of Pathology

Education

Degrees

  • M.D., Johns Hopkins University School of Medicine (Maryland) (1974)

Research & Publications

Research Summary

The goal of our research is to develop new approaches to the prevention or treatment of cancers through a better understanding of the genes and pathways underlying their pathogenesis.

Our major focus is on cancers of the colon and rectum. We have shown that each colon neoplasm arises from a clonal expansion of one transformed cell. This expansion gives rise to a small benign colon tumor (called a polyp or adenoma). This clonal expansion and subsequent growth of the tumors appears to be caused by mutations in oncogenes and tumor suppressor genes, and the whole process is accelerated by defects in genes required for maintaining genetic instability. Mutations in four or five such genes are required for a malignant tumor to form, while fewer mutations suffice for benign tumorigenesis. As the mutations accumulate, the tumors become progressively more dangerous.

Current studies are aimed at further characterization of the mechanisms through which these genes act, the identification of other genes that play a role in this tumor type, and the application of this knowledge to patient management. Genetic tests for risk assessment, pre-symptomatic detection of tumors, and prognosis have been devised and are constantly being improved. Novel therapeutic agents that target the specific defects in cancer are under development.?

 

Lab Website: Bert Vogelstein Laboratory

Selected Publications

View all on Pubmed

Baker, S.J., Fearon, E.R., Nigro, J.M., Hamilton, S.R., Preisinger, A.C., Jessup, J.M., vanTuinen, P., Ledbetter, D.H., Barker, D.F., Nakamura, Y., White, R., Vogelstein, B. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science 244: 217-221, 1989.

Nishisho, I., Nakamura, Y., Miyoshi, Y., Miki, Y., Ando, H., Horii, A., Koyama, K., Utsunomiya, J., Baba, S., Hedge, P., Markham, A., Krush, A.J., Petersen, G., Hamilton, S.R., Nilbert, M.C., Levy, D.B., Bryan, T.M., Preisinger, A.C., Smith, K.J., Su, L.-K., Kinzler, K.W., Vogelstein, B. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 253: 665-669, 1991.

Kern, S.E., Kinzler, K.W., Bruskin, A., Jarosz, D., Friedman, P., Prives, C., Vogelstein, B. Identification of p53 as a sequence-specific DNA-binding protein. Science 252: 1708-1711, 1991.

Peltomaki, P., Aaltonen, L.A., Sistonen, P., Pylkkanen, L., Mecklin, J.-P., Jarvinen, H., Green, J.S., Jass, J.R., Weber, J.L., Leach, F.S., Petersen, G.M., Hamilton, S.R., de la Chapelle, A., Vogelstein, B. Genetic Mapping of a locus predisposing to human colorectal cancer. Science 260: 810-812, 1993.

Wood, L.D., Parsons, D.W., Jones, S., Lin, J., Sjöblom, T., Leary, R,J., Shen, D., Boca, S.M., Barber, T., Ptak, J., Silliman, N., Szabo, S., Dezso, Z., Ustyanksky, V., Nikolskaya, T., Nikolsky, Y., Karchin, R., Wilson, P.A., Kaminker, J.A., Zhang, Z., Croshaw, R., Willis, J., Dawson, D., Shipitsin, M., Willson, J.K.V., Sukumar, S., Polyak, K., Park, B.H., Pethiyagoda, C.L., Pant, P.V.K., Ballinger, D.G., Sparks, A.B., Hartigan, J., Smith, D. R., Suh, E., Papadopoulos, N., Buckhaults, P., Markowitz,S.D., Parmigiani, G., Kinzler, K.W., Velculescu, V.E. and Vogelstein, B. The genomic landscapes of human breast and colorectal cancers. Science 318: 1108-1113, 2007.

Academic Affiliations & Courses

Graduate Program Affiliation

Program in Human Genetics
Cellular and Molecular Medicine

Videos & Media

Beating Cancer: Precision Immunotherapy

Recent News Articles and Media Coverage

Howard Hughes Medical Institute: Career Highlights

When the Sun Goes Down: Bert "Rockin'' Doc" Vogelstein Rocks the Town

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