Bert Vogelstein
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Bert Vogelstein (born 1949) is director of the Ludwig Center, Clayton Professor of Oncology and Pathology and a
Howard Hughes Medical Institute The Howard Hughes Medical Institute (HHMI) is an American non-profit medical research organization based in Chevy Chase, Maryland. It was founded in 1953 by Howard Hughes, an American business magnate, investor, record-setting pilot, engineer, fil ...
investigator at The
Johns Hopkins Johns Hopkins (May 19, 1795 – December 24, 1873) was an American merchant, investor, and philanthropist. Born on a plantation, he left his home to start a career at the age of 17, and settled in Baltimore, Maryland where he remained for most ...
Medical School and
Sidney Kimmel Comprehensive Cancer Center The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University is an NCI-Designated Comprehensive Cancer Center in Baltimore, MD. It was established in 1973 and received its NCI designation that same year as one of the first designated ca ...
. A pioneer in the field of cancer genomics, his studies on colorectal cancers revealed that they result from the sequential accumulation of mutations in
oncogenes An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.
and
tumor suppressor genes A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or red ...
. These studies now form the paradigm for modern cancer research and provided the basis for the notion of the somatic evolution of cancer.


Research

In the 1980s, Vogelstein developed new experimental approaches to study human tumors. His studies of various stages of colorectal cancers led him to propose a specific model for human tumorigenesis in 1988. In particular, he suggested that "cancer is caused by sequential mutations of specific oncogenes and tumor suppressor genes". The first tumor suppressor gene validating this hypothesis was that encoding
p53 p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...
. The p53 protein was discovered 10 years earlier by several groups, including that of David Lane and Lionel Crawford, Arnold Levine, and Lloyd Old. But there was no evidence that p53 played a major role in human cancers, and the gene encoding p53 (TP53) was thought to be an oncogene rather than a tumor suppressor gene. In 1989, Vogelstein and his students discovered that TP53 not only played a role in human tumorigenesis, but that it was a common denominator of human tumors, mutated in the majority of them. He then discovered the mechanism through which TP53 suppresses tumorigenesis. Prior to these studies, the only biochemical function attributed to p53 was its binding to heat shock proteins. Vogelstein and his colleagues demonstrated that p53 had a much more specific activity: it bound DNA in a sequence-specific manner. They precisely defined its consensus recognition sequence and showed that virtually all p53 mutations found in tumors resulted in loss of the sequence-specific transcriptional activation properties of p53. They subsequently discovered genes that are directly activated by p53 to control cell birth and cell death. His group's more recent studies examining the entire compendium of human genes have shown that the TP53 gene is more frequently mutated in cancers than any other gene . In 1991, Vogelstein and long-time colleague Kenneth W. Kinzler, working with Yusuke Nakamura in Japan, discovered another tumor suppressor gene. This gene, called APC, was responsible for
Familial Adenomatous Polyposis Familial adenomatous polyposis (FAP) is an autosomal dominant inherited condition in which numerous Adenomatous polyps, adenomatous Colorectal polyp, polyps form mainly in the epithelium of the colon (anatomy), large intestine. While these polyps s ...
(FAP), a syndrome associated with the development of numerous small benign tumors, some of which progress to cancer. This gene was independently discovered by Ray White's group at the University of Utah. Vogelstein and Kinzler subsequently showed that non-hereditary (somatic) mutations of APC initiate most cases of colon and rectal cancers. They also showed how APC functions – through binding to beta-catenin and stimulating its degradation. Vogelstein and Kinzler worked with Albert de la Chapelle and Lauri Aaltonen at the U. Helsinki to identify the genes responsible for Hereditary NonPolyposis Colorectal Cancer (
HNPCC Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome is an autosomal dominant genetic condition that is associated with a high risk of colon cancer as well as other cancers including endometrial cancer (second most common), ovary, ...
), the other major form of heritable colorectal tumorigenesis. They were the first to localize one of the major causative genes to a specific chromosomal locus through linkage studies. This localization soon led them and other groups to identify repair genes such as MSH2 and MLH1 that are responsible for most cases of this syndrome. In the early 2000s, Vogelstein and Kinzler, working with
Victor Velculescu Victor E. Velculescu (born August 16, 1970) is a Professor of Oncology and Co-Director of Cancer Biology at Johns Hopkins University School of Medicine. He is internationally known for his discoveries in genomics and cancer research. Early lif ...
, Aman Amer Zakar, Mustak Akbar Zakar, Bishwas Banerjee, Carmen Flohlar, Couleen Mathers, Farheen Zuber Mohmed Patel, Nicholas Papadopoulos, and others in their group, began to perform large scale experiments to identify mutations throughout the genome. They were to perform "exomic sequencing", meaning determination of the sequence of every protein-encoding gene in the human genome. The first analyzed tumors included those of the colon, breast, pancreas, and brain. These studies outlined the landscapes of human cancer genomes, later confirmed by massively parallel sequencing of many different tumor types by laboratories throughout the world. In the process of analyzing all the protein-encoding genes within cancers, Vogelstein and his colleagues discovered several novel genes that play important roles in cancer, such as PIK3CA, IDH1, IDH2, ARID1A, ARID2, ATRX, DAXX, MLL2, MLL3, CIC, and RNF43. Vogelstein pioneered the idea that somatic mutations represent uniquely specific biomarkers for cancer, creating the field now called "liquid biopsies". Working with post-doctoral fellow David Sidransky in the early 1990s, he showed that such somatic mutations were detectable in the stool of colorectal cancer patients and the urine of bladder cancer patients. For this purpose, they developed "Digital PCR" in which DNA molecules are examined one-by-one to determine whether they are normal or mutated. One of the techniques they invented for Digital PCR is called "
BEAMing BEAMing, which stands for beads, emulsion, amplification, magnetics, is a highly sensitive digital PCR method that combines emulsion PCR and flow cytometry to identify and quantify specific somatic mutations present in DNA. Process BEAMing begin ...
", in which the PCR is carried out on magnetic beads in water-in-oil emulsions. BEAMing is now one of the core technologies used in some next-generation, massively parallel sequencing instruments. More recently, they developed a digital-PCR based technique called SafeSeqS, in which every DNA template molecule is recognized by a unique molecular barcode. SafeSeqS dramatically enhances the ability to identify rare variants among DNA sequences, allowing such variants to be detected when they are present in only 1 in more than 10,000 total DNA molecules. In mid-2019, Vogelstein started collaborating with the group of
Martin Nowak Martin Andreas Nowak (born April 7, 1965) is an Austrian-born professor of mathematical biology, at Harvard University since 2003. He is one of the leading researchers in the field that studies the role of cooperation in evolution. Nowak has hel ...
at
Harvard University Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of higher le ...
. Together with their groups, they developed mathematical models to explain the evolution of resistance against targeted therapies. They showed that the sequential administration of multiple targeted drugs precludes any chance for cure — even when there are no possible mutations that can confer cross-resistance to both drugs. Thus, simultaneous combination of targeted therapies (as opposed to sequential) is the preferred strategy as there is at least a potential for cure.


Citations

Vogelstein has published nearly 600 scientific papers. Vogelstein's research papers have been cited over 430,000 times. In 2016
Semantic Scholar Semantic Scholar is an artificial intelligence–powered research tool for scientific literature developed at the Allen Institute for AI and publicly released in November 2015. It uses advances in natural language processing to provide summaries ...
AI program included Vogelstein on its list of top ten most influential biomedical researchers.


Awards

* 1990 – The Bristol Myers Squibb Award for "Distinguished Achievement in Cancer Research" * 1992 – The Young Investigator Award from the American Federation for Clinical Research, now the American Federation for Medical Research * 1992 – The
Gairdner Foundation International Award The Canada Gairdner International Award is given annually by the Gairdner Foundation at a special dinner to five individuals for outstanding discoveries or contributions to medical science. Receipt of the Gairdner is traditionally considered a p ...
in Science * 1992 – The American Cancer Society Medal of Honor * 1993 – The Shacknai Memorial Prize from the
Hebrew University The Hebrew University of Jerusalem (HUJI; he, הַאוּנִיבֶרְסִיטָה הַעִבְרִית בִּירוּשָׁלַיִם) is a public research university based in Jerusalem, Israel. Co-founded by Albert Einstein and Dr. Chaim Weiz ...
* 1993 – The Pezcoller Foundation Award from the
American Association for Cancer Research The American Association for Cancer Research (AACR) is the world's oldest and largest professional association related to cancer research. Based in Philadelphia, the AACR focuses on all aspects of cancer research, including basic, clinical, and t ...
* 1993 – The
Richard Lounsbery Award The Richard Lounsbery Award is given to American and French scientists, 45 years or younger, in recognition of "extraordinary scientific achievement in biology and medicine." The Award alternates between French and American scientists, and is aw ...
from the National Academy of Sciences * 1993 – The Baxter Award from the
Association of American Medical Colleges The Association of American Medical Colleges (AAMC) is a nonprofit organization based in Washington, D.C. that was established in 1876. It represents medical schools, teaching hospitals, and academic and scientific societies, while providing serv ...
* 1994 – The
Dickson Prize The Dickson Prize in Medicine and the Dickson Prize in Science were both established in 1969 by Joseph Z. Dickson and Agnes Fischer Dickson. Dickson Prize in Medicine The Dickson Prize in Medicine is awarded annually by the University of Pittsburg ...
from the
University of Pittsburgh The University of Pittsburgh (Pitt) is a public state-related research university in Pittsburgh, Pennsylvania. The university is composed of 17 undergraduate and graduate schools and colleges at its urban Pittsburgh campus, home to the universit ...
* 1994 – The
Ernst Schering Prize The Ernst Schering Prize is awarded annually by the Ernst Schering Foundation for especially outstanding basic research in the fields of medicine, biology or chemistry anywhere in the world. Established in 1991 by the Ernst Schering Research Found ...
* 1994 – The Passano Award from the
Passano Foundation The Passano Foundation, established in 1945, provides an annual award to a research scientist whose work – done in the United States – is thought to have immediate practical benefits. Many Passano laureates have subsequently won the Nobel Priz ...
* 1994 – The
Howard Taylor Ricketts Howard Taylor Ricketts (February 9, 1871 – May 3, 1910) was an American pathologist after whom the family Rickettsiaceae and the order Rickettsiales are named. He was born in Findlay, Ohio. In the early part of his career, Ricketts undertook ...
Award from the
University of Chicago The University of Chicago (UChicago, Chicago, U of C, or UChi) is a private research university in Chicago, Illinois. Its main campus is located in Chicago's Hyde Park neighborhood. The University of Chicago is consistently ranked among the b ...
* 1995 – The David A. Karnofsky Memorial Award from the
American Society of Clinical Oncology The American Society of Clinical Oncology (ASCO) is a professional organization representing physicians of all oncology sub-specialties who care for people with cancer. Founded in 1964 by Fred Ansfield, Harry Bisel, Herman Freckman, Arnoldus G ...
* 1995 – The Clowes Memorial Award from the
American Association for Cancer Research The American Association for Cancer Research (AACR) is the world's oldest and largest professional association related to cancer research. Based in Philadelphia, the AACR focuses on all aspects of cancer research, including basic, clinical, and t ...
* 1997 – The William Beaumont Prize in Gastroenterology from the
American Gastroenterological Association The American Gastroenterological Association (AGA) is a medical association of gastroenterologists. Approximately 16,000 scientists and physicians are members of the organization. Overview The American Gastroenterological Association is a prof ...
* 1997 – Golden Plate Award of the
American Academy of Achievement The American Academy of Achievement, colloquially known as the Academy of Achievement, is a non-profit educational organization that recognizes some of the highest achieving individuals in diverse fields and gives them the opportunity to meet o ...
* 1998 – The
Louisa Gross Horwitz Prize The Louisa Gross Horwitz Prize for Biology or Biochemistry is an annual prize awarded by Columbia University to a researcher or group of researchers who have made an outstanding contribution in basic research in the fields of biology or biochemist ...
* 1998 – The
Paul Ehrlich and Ludwig Darmstaedter Prize The Paul Ehrlich and Ludwig Darmstaedter Prize is an annual award bestowed by the since 1952 for investigations in medicine. It carries a prize money of 120,000 Euro. The prize awarding ceremony is traditionally held on March 14, the birthday of N ...
from the Paul Ehrlich Foundation * 1998 – The
William Allan Award The William Allan Award, given by the American Society of Human Genetics, was established in 1961 in memory of William Allan (1881–1943), one of the first American physicians to conduct extensive research in human genetics. The William Allan ...
from the American Society of Human Genetics * 2000 – The
Charles S. Mott Prize The Charles S. Mott Prize was awarded annually by the General Motors Cancer Research Foundation as one of a trio of scientific prizes entirely devoted to cancer research, the other two being the Charles F. Kettering Prize and the Alfred P. Sloan, J ...
from the General Motors Cancer Research Foundation * 2001 – The
Harvey Prize Harvey Prize is an annual Israeli award for breakthroughs in science and technology, as well as contributions to peace in the Middle East granted by the Technion in Haifa. History The prize is named for industrialist and inventor Leo Harvey. T ...
in Human Health from the Technion * 2003 – The John Scott Award from the John Scott Trust * 2004 – The
Prince of Asturias Awards The Princess of Asturias Awards ( es, Premios Princesa de Asturias, links=no, ast, Premios Princesa d'Asturies, links=no), formerly the Prince of Asturias Awards from 1981 to 2014 ( es, Premios Príncipe de Asturias, links=no), are a series of a ...
in Science * 2007 – The
Pasarow Award The Robert J. And Claire Pasarow Foundation Medical Research Awards were awarded annually for distinguished accomplishment in areas of investigation that included neuropsychiatry, cardiovascular disease, and cancer research. The program ran from 1 ...
for Medical Research * 2011 – The Charles Rodolphe Brupbacher Prize for Cancer Research * 2012 – The New York Academy of Medicine Medal for Distinguished Contributions to Biomedical Science * 2012 – The Pioneer in Science Award from the American Research Forum * 2013 –
Breakthrough Prize in Life Sciences The Breakthrough Prize in Life Sciences is a scientific award, funded by internet entrepreneurs Mark Zuckerberg and Priscilla Chan of Facebook; Sergey Brin of Google; entrepreneur and venture capitalist Yuri Milner; and Anne Wojcicki, one of the ...
* 2014 – Warren Triennial Prize * 2015 – Dr. Paul Janssen Award for Biomedical Research * 2018
The Dan David Prize for Personalized Medicine
* 2019 –
Gruber Prize in Genetics The Gruber Prize in Genetics, established in 2001, is one of three international awards worth US$500,000 made by the Gruber Foundation, a non-profit organization based at Yale University in New Haven, Connecticut. The Genetics Prize honors leadi ...
* 2019 –
Albany Medical Center Prize The Albany Medical Center Prize in Medicine and Biomedical Research is the United States' second highest value prize in medicine and biomedical research, awarded by the Albany Medical Center. Among prizes for medicine worldwide, the Albany Medical ...
* 2020 – ''
The Times ''The Times'' is a British daily national newspaper based in London. It began in 1785 under the title ''The Daily Universal Register'', adopting its current name on 1 January 1788. ''The Times'' and its sister paper ''The Sunday Times'' (fou ...
'' 'Science Power List' * 2021 –
Japan Prize is awarded to people from all parts of the world whose "original and outstanding achievements in science and technology are recognized as having advanced the frontiers of knowledge and served the cause of peace and prosperity for mankind." The P ...


Affiliations


References


External links


The Official Site of Louisa Gross Horwitz Prize
{{DEFAULTSORT:Vogelstein, Bert Howard Hughes Medical Investigators Members of the United States National Academy of Sciences Richard-Lounsbery Award laureates Johns Hopkins Hospital physicians American oncologists 1949 births Members of the European Molecular Biology Organization Living people People from Baltimore County, Maryland University of Pennsylvania alumni Johns Hopkins School of Medicine alumni 20th-century American Jews 21st-century American Jews Members of the American Philosophical Society Members of the National Academy of Medicine