Bert Vogelstein

The Bert Vogelstein Laboratory seeks 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 the 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. Bert Vogelstein, M.D. graduated summa cum laude with distinction in mathematics from the University of Pennsylvania. He obtained his medical degree and performed clinical training in pediatrics at the Johns Hopkins University School of Medicine. After postdoctoral training in new techniques in molecular biology at the National Cancer Institute, 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. He is a Howard Hughes Medical Institute investigator. Bert Vogelstein aims to develop new prevention and treatment strategies based on the genetic alterations that drive tumorigenesis. Vogelstein and his team have identified some of the most common mutations that initiate tumors or cause them to progress, and have characterized the signaling pathways through which they act. One of the team’s most important discoveries in this area was that a relatively small number of genes plays a major role in most human cancer types. Currently, they focus on using this core set of cancer driver genes to develop novel methods for identifying cancers at an early stage, and to devise novel therapeutic approaches for exploiting the vulnerabilities these mutations cause. Dr. Bert Vogelstein was the first to elucidate the molecular basis of a common human cancer. 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 attended the University of Pennsylvania, where he graduated Summa Cum Laude with distinction in mathematics. He obtained his medical degree at the Johns Hopkins University School of Medicine and performed his residency in pediatrics at the Johns Hopkins Hospital. Following his clinical training, Dr. Vogelstein completed a post-doctoral fellowship at the National Cancer Institute, focusing on the development of new techniques in molecular biology. He returned to Johns Hopkins as an Assistant Professor in Oncology, and is now Clayton Professor of Oncology and Pathology. Dr. Vogelstein also holds a joint appointment in Molecular Biology and Genetics at JHU and is an Investigator of the Howard Hughes Medical Institute. He is currently the Director of the Ludwig Center for Cancer Genetics & Therapeutics at the Johns Hopkins Kimmel Cancer Center. 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. Dr. Bert Vogelstein is a pioneer in cancer genetics. As early as 1988, his research on colorectal cancer was transforming when he proposed that cancers result from the gradual accumulation of mutations in specific cancer-causing genes (oncogenes) and tumor suppressor genes. This model forms the backbone for modern cancer research and has greatly influenced the diagnosis and treatment of cancer. His team’s novel experiments demonstrated that colorectal tumors represent clonal expansions of mutated cells and that colorectal tumors are characterized by mutations of the p53 tumor suppressor gene. They co-discovered the tumor suppressor gene, adenomatous polyposis coli (APC), showing that mutations initiate colorectal neoplasia, many liver cancers, and other tumor types. He and his colleagues developed innovative DNA sequencing techniques and his research has revealed important insights into tumor heterogeneity, clonal evolution, the interplay between genetics and environmental factors in cancer development, and biomarkers that can be employed for the early detection of cancer. Now that most of the genetic changes responsible for human cancer have been identified, Dr. Vogelstein focuses on developing therapies and diagnostic methods for earlier cancer detection. In the late 1980s, Bert Vogelstein, M.D., became the first scientist to unravel the molecular basis of one of the most common genetic mutations in all cancers: errors in the p53 gene. That discovery led to the creation of a specific model for human carcinogenesis, fondly known as Vogelgram, and is widely credited with laying the groundwork for much of modern cancer genetics research today. With his colleague, Kenneth Kinzler, Ph.D., a co-director of the Ludwig Center at Johns Hopkins Kimmel Cancer Center, Dr. Vogelstein helped define the molecular pathways cancers use to gain an advantage over normal cells to cause disease. Initially, the pioneering work of these two scientists focused on colorectal cancers, demonstrating that cumulative p53 mutations suppress ordinary cellular mechanisms used to keep malignancies under control. But their painstaking efforts in this one cancer now serves as a paradigm for detecting genetic errors in many other cancers. Dr. Vogelstein and the Hopkins team have focused attention on prevention and detection strategies that exploit the genetic vulnerabilities identified. One involves a liquid biopsy test that scours the blood for signs of early cancer when it may be preventable or even curable. The test, which measures mutated DNA and snippets of tumor-associated proteins, is one of several approaches under study world-wide. For his contributions to cancer research, Dr. Vogelstein has been honored many times, including the Distinguished Scientist Award from the Association of American Cancer Institutes and as one of the first-ever recipients of the Breakthrough Prize in Life Sciences. As early as 2003, he already held the distinction of being the most highly cited scientist in the world, with over 300,000 citations to his published articles.