Bert Vogelstein

Source: Wikipedia, the free encyclopedia.
Bert Vogelstein
Joshua T. Vogelstein, and one more, Grandchildren: 5
AwardsBreakthrough Prize in Life Sciences (2013)[1]
Warren Triennial Prize (2014)[2]
Scientific career
FieldsOncology, Pathology
InstitutionsJohns Hopkins School of Medicine
Doctoral students
  • Kenneth Kinzler[3]
Websitewww.hhmi.org/research/investigators/vogelstein_bio.html

Bert Vogelstein (born 1949) is director of the Ludwig Center, Clayton Professor of Oncology and Pathology and a

tumor suppressor genes
. 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.[5] 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".[6][7][8]

The first tumor suppressor gene validating this hypothesis was that encoding

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.[9][10] 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.[11][12] They subsequently discovered genes that are directly activated by p53 to control cell birth and cell death.[13][14] 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 .[15][16][12][17][18][19]

In 1991, Vogelstein and long-time colleague

Familial Adenomatous Polyposis (FAP), a syndrome associated with the development of numerous small benign tumors, some of which progress to cancer.[20][21] 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.[22][23]

Vogelstein and Kinzler worked with

HNPCC), 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.[24][25][26][27]

In the early 2000s, Vogelstein and Kinzler, working with

PIK3CA,[29] IDH1,[30] IDH2,[30] ARID1A,[31] ARID2, ATRX,[32] DAXX,[32] MLL2, MLL3, CIC, and RNF43.[33][34][35][36]

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.[37][38] For this purpose, they developed "Digital PCR" in which DNA molecules are examined one-by-one to determine whether they are normal or mutated.[39] One of the techniques they invented for Digital PCR is called "BEAMing", in which the PCR is carried out on magnetic beads in water-in-oil emulsions.[40] 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.[41][42][43][44][45]

In mid-2019, Vogelstein started collaborating with the group of Martin Nowak at Harvard University. Together with their groups, they developed mathematical models to explain the evolution of resistance against targeted therapies.[46] 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.[47]

Citations

Vogelstein has published nearly 600 scientific papers. Vogelstein's research papers have been cited over 430,000 times.[48]

In 2016 Semantic Scholar AI program included Vogelstein on its list of top ten most influential biomedical researchers.[49]

Awards

Affiliations

References

  1. ^ "Breakthrough Prize – Life Sciences Breakthrough Prize Laureates – Bert Vogelstein". breakthroughprize.org.
  2. ^ a b "Mass. General Hospital's Warren Triennial Prize to honor Bert Vogelstein, MD - Massachusetts General Hospital, Boston, MA". Archived from the original on 2015-02-21. Retrieved 2015-02-21.
  3. PMID 25550474
    – via clinchem.aaccjnls.org.
  4. ^ "Interview with Bert Vogelstein". Archived from the original on 2013-06-03. Retrieved 2010-04-30.
  5. PMID 2982210
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  48. ^ "1360 Highly Cited Researchers (h>100) according to their Google Scholar Citations public profiles". Retrieved 1 February 2017.
  49. ^ "Who's the most influential biomedical scientist? Computer program guided by artificial intelligence says it knows". Science | AAAS. 17 October 2017. Retrieved 16 June 2021.
  50. ^ "Bristol Myers Squibb Award" (PDF). Archived from the original (PDF) on 2012-11-14. Retrieved 2015-04-02.
  51. ^ "Past Recipients / Bert Vogelstein". Canada Gairdner Award web site.
  52. ^ "Team BCPS: creating a culture of deliberate excellence, Baltimore County Public Schools". Archived from the original on 2017-09-20. Retrieved 2015-04-02.
  53. ^ "Nominations Open for 2010 Pezcoller Foundation–AACR International Award for Cancer Research". www.newswise.com.
  54. ^ "Richard Lounsbery Award". National Academy of Sciences. Retrieved 17 October 2022.
  55. ^ Baxter Award
  56. ^ "Bert Vogelstein Ernst Schering Prize 1994". Schering Stiftung. Retrieved 17 October 2022.
  57. ^ "Passano Award". Archived from the original on 2016-02-09. Retrieved 2015-04-02.
  58. ^ "Howard T. Ricketts Prize and Lecture -". biologicalsciences.uchicago.edu. University of Chicago. Retrieved 17 October 2022.
  59. ^ David A. Karnofsky Memorial Award
  60. ^ "AACR-G.H.A. Clowes Award for Outstanding Basic Cancer Research: Past Recipients".
  61. ^ William Beaumont Prize
  62. American Academy of Achievement
    .
  63. ^ "Horwitz Prize Awardees". cuimc.columbia.ed. Columbia University. 20 June 2018. Retrieved 17 October 2022.
  64. ^ "Prize Winners of the Paul Ehrlich and Ludwig Darmstaedter Prize" (PDF). The Paul Ehrlich Foundation. Retrieved 17 October 2022.
  65. ^ "Past Award Recipients - William Allan Award". ASHG. American Society of Human Genetics. Retrieved 17 October 2022.
  66. ^ "Harvey Prize". Technion Web Development Group. Retrieved 17 October 2022.
  67. ^ "Association for Molecular Pathology Award Honors".
  68. ^ "John Scott Award recipients". Archived from the original on 2010-07-01.
  69. ^ "Prince of Asturias Award for Technical & Scientific Research 2004".
  70. ^ "Cancer Research Prize". Charles Rodolphe Brupbacher Foundation. Archived from the original on 2015-04-03.
  71. ^ "Breakthrough Prize – Life Sciences Breakthrough Prize Laureates – Bert Vogelstein". BreakThroughPrize. Retrieved 17 October 2022.
  72. ^ Warren Triennial Prize
  73. ^ "Bert Vogelstein, M.D., Wins 2015 Dr. Paul Janssen Award". UAB "JOHNSON & JOHNSON". 17 June 2015. Retrieved 17 October 2022.
  74. ^ "US researchers receive Dan David Prize for outstanding cancer research". The Jerusalem Post | JPost.com. 8 February 2018. Retrieved 2020-04-21.
  75. ^ "May 2018: Dan David Prize laureates in Personalized Medicine". physics.tau.ac.il. Retrieved 2020-04-21.
  76. ^ "2019 Gruber Genetics Prize". The Gruber Foundation. Retrieved 17 October 2022.
  77. ^ "Albany Medical Center Announces Winners Of Prize In Medicine". WAMC Northeast Public Radio. 24 September 2019. Retrieved 17 October 2022.
  78. ISSN 0140-0460
    . Retrieved 2020-05-26.
  79. ^ "The Japan Prize Foundation". www.japanprize.jp.
  80. ^ "APS Member History". search.amphilsoc.org. Retrieved 2021-12-16.

External links