Karen Vousden
Encyclopedia
Karen Heather Vousden, CBE
, FRS, FRSE
, FMedSci
is a British
medical researcher. She is known for her work on the tumour suppressor protein, p53
, and in particular her discovery of the important regulatory role of Mdm2
, an attractive target for anti-cancer agents
. She is currently the director of Cancer Research UK
's Beatson Institute of Cancer Research
in Glasgow
, UK.
, Vousden gained a BSc
degree in genetics
and microbiology
(1978) and a PhD
degree in genetics
(1982) from Queen Mary College
, University of London
. Her early post-doctoral positions were with Chris Marshall at the Institute of Cancer Research
, London
, UK (1981–5) and Douglas Lowy at the National Cancer Institute
, Bethesda
, USA (1985–7).
From 1987 to 1995, she led the Human Papillomavirus Group at the Ludwig Institute for Cancer Research
, London, UK. In 1995, she joined the National Cancer Institute in Frederick
, USA, serving successively as head of the Molecular Carcinogenesis section of the ABL-Basic Research Program (1995–7), director of the Molecular Virology and Carcinogenesis Laboratory (1997–8), interim director of the ABL-Basic Research Program (1998–9) and chief of the Regulation of Cell Growth Laboratory, Division of Basic Sciences (1999–2002).
Since 2002, she has been the director of the Cancer Research UK
's Beatson Institute of Cancer Research
in Glasgow
, UK, where she has overseen a £15 million expansion. She also leads the institute's Tumour Suppression research group.
es (HPVs), which are associated with cervical cancer
. With Douglas Lowy and others, she pinpointed the specific viral oncoproteins required by HPV-16 to immortalise
epithelial cells. She was also part of a group which showed that E6, one of the HPV-16 oncoproteins, binds to the human tumour suppressor protein p53
in vivo, resulting in its degradation.
. Sometimes called "the guardian of the genome", p53 plays a critical role in preventing the development of tumours by inducing cells subject to stress, such as DNA
damage, to commit suicide via the apoptosis
mechanism. Vousden's work has been important in delineating the mechanism of this process. With Katsunori Nakano, she discovered a key component in the apoptosis pathway triggered by p53, the protein PUMA
(P53 Upregulated Modulator of Apoptosis).
To prevent it being activated inappropriately, p53 is strictly controlled in the normal cell. Vousden discovered that a key element in this regulation is the protein Mdm2
. With Allan Weissman and others, she showed that Mdm2 is a ubiquitin ligase
which targets p53 for degradation by the proteasome
, thus ensuring levels of the protein remain low when the cell is not under stress.
Reactivating p53 can inhibit the growth of some tumours, making Mdm2 an attractive target for cancer therapeutics. As Mdm2 targets only a small number of proteins for destruction, an inhibitor might have few side effects. A major focus of Vousden's recent work has been investigating the structure of Mdm2 and seeking molecules that inhibit it; a group of low-molecular-weight compounds (discovered in collaboration with the Department of Chemistry at the University of Glasgow
) have recently shown promise in cell-culture studies. Mdm2 inhibitors have also been discovered by researchers at Hoffmann–La Roche and the Karolinska Institute
.
p53 can also help to prevent or repair minor damage to the genome under conditions of low stress. Vousden's group have recently discovered a novel p53-regulated protein, TIGAR
(T-p53 Inducible Glycolysis and Apoptosis Regulator), which can reduce oxidative stress
in cells and might mediate part of this effect of p53.
(2003), Royal Society of Edinburgh
(2004) and the Academy of Medical Sciences
(2006); she was also elected a member of the European Molecular Biology Organization
in 2004. The Institute of Cancer Research
awarded her an Honorary Doctorate in Science (Medicine) in 2006. She will give the Sir Frederick Gowland Hopkins Memorial Lecture of the Biochemical Society
in 2008.
In 2004, The Scotsman
named Vousden among the 25 most powerful Scottish women.
Vousden was appointed Commander of the Order of the British Empire (CBE) in the 2010 New Year Honours.
Order of the British Empire
The Most Excellent Order of the British Empire is an order of chivalry established on 4 June 1917 by George V of the United Kingdom. The Order comprises five classes in civil and military divisions...
, FRS, FRSE
Royal Society of Edinburgh
The Royal Society of Edinburgh is Scotland's national academy of science and letters. It is a registered charity, operating on a wholly independent and non-party-political basis and providing public benefit throughout Scotland...
, FMedSci
Academy of Medical Sciences
The Academy of Medical Sciences is the United Kingdom's national academy of medical sciences. It was established in 1998 on the recommendation of a group that was chaired by Michael Atiyah. Its president is John Irving Bell....
is a British
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
medical researcher. She is known for her work on the tumour suppressor protein, p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
, and in particular her discovery of the important regulatory role of Mdm2
Mdm2
Mdm2 is an important negative regulator of the p53 tumor suppressor. It is the name of a gene as well as the protein encoded by that gene. Mdm2 protein functions both as an E3 ubiquitin ligase that recognizes the N-terminal trans-activation domain of the p53 tumor suppressor and an inhibitor of...
, an attractive target for anti-cancer agents
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
. She is currently the director of Cancer Research UK
Cancer Research UK
Cancer Research UK is a cancer research and awareness charity in the United Kingdom, formed on 4 February 2002 by the merger of The Cancer Research Campaign and the Imperial Cancer Research Fund. Its aim is to reduce the number of deaths from cancer. As the world's largest independent cancer...
's Beatson Institute of Cancer Research
Beatson Oncology Centre
The Beatson West of Scotland Cancer Centre is a specialised cancer care centre in Glasgow, Scotland. Until recently it had facilities in Gartnavel General Hospital, the Western Infirmary and Glasgow Royal Infirmary...
in Glasgow
Glasgow
Glasgow is the largest city in Scotland and third most populous in the United Kingdom. The city is situated on the River Clyde in the country's west central lowlands...
, UK.
Education and career
After attending Gravesend Grammar School for GirlsGravesend Grammar School for Girls
Mayfield Grammar School is a selective secondary school located off the B261 in Gravesend, Kent, England. The school accepts girls at age 11 by examination and both girls and boys at age 16, based on their GCSE results...
, Vousden gained a BSc
Bachelor of Science
A Bachelor of Science is an undergraduate academic degree awarded for completed courses that generally last three to five years .-Australia:In Australia, the BSc is a 3 year degree, offered from 1st year on...
degree in genetics
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
and microbiology
Microbiology
Microbiology is the study of microorganisms, which are defined as any microscopic organism that comprises either a single cell , cell clusters or no cell at all . This includes eukaryotes, such as fungi and protists, and prokaryotes...
(1978) and a PhD
Doctor of Philosophy
Doctor of Philosophy, abbreviated as Ph.D., PhD, D.Phil., or DPhil , in English-speaking countries, is a postgraduate academic degree awarded by universities...
degree in genetics
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
(1982) from Queen Mary College
Queen Mary, University of London
Queen Mary, University of London is a public research university located in London, United Kingdom and a constituent college of the federal University of London...
, University of London
University of London
-20th century:Shortly after 6 Burlington Gardens was vacated, the University went through a period of rapid expansion. Bedford College, Royal Holloway and the London School of Economics all joined in 1900, Regent's Park College, which had affiliated in 1841 became an official divinity school of the...
. Her early post-doctoral positions were with Chris Marshall at the Institute of Cancer Research
Institute of Cancer Research
The Institute of Cancer Research is a cancer research institute located in London, United Kingdom and a constituent college of the federal University of London. The ICR was founded in 1909 as a research department of the Royal Marsden Hospital and joined the University of London in 2003...
, London
London
London is the capital city of :England and the :United Kingdom, the largest metropolitan area in the United Kingdom, and the largest urban zone in the European Union by most measures. Located on the River Thames, London has been a major settlement for two millennia, its history going back to its...
, UK (1981–5) and Douglas Lowy at the National Cancer Institute
National Cancer Institute
The National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...
, Bethesda
Bethesda, Maryland
Bethesda is a census designated place in southern Montgomery County, Maryland, United States, just northwest of Washington, D.C. It takes its name from a local church, the Bethesda Meeting House , which in turn took its name from Jerusalem's Pool of Bethesda...
, USA (1985–7).
From 1987 to 1995, she led the Human Papillomavirus Group at the Ludwig Institute for Cancer Research
Ludwig Institute for Cancer Research
The Ludwig Institute for Cancer Research Ltd is a global non-profit medical research institute that undertakes laboratory and clinical research into cancer, conducting and sponsoring its own early-phase clinical trials to investigate its discoveries....
, London, UK. In 1995, she joined the National Cancer Institute in Frederick
Frederick
-Royalty:Austria* Frederick I, Duke of Austria , Duke of Austria from 1195–1198* Frederick II, Duke of Austria , last Duke of Austria from the Babenberg dynasty...
, USA, serving successively as head of the Molecular Carcinogenesis section of the ABL-Basic Research Program (1995–7), director of the Molecular Virology and Carcinogenesis Laboratory (1997–8), interim director of the ABL-Basic Research Program (1998–9) and chief of the Regulation of Cell Growth Laboratory, Division of Basic Sciences (1999–2002).
Since 2002, she has been the director of the Cancer Research UK
Cancer Research UK
Cancer Research UK is a cancer research and awareness charity in the United Kingdom, formed on 4 February 2002 by the merger of The Cancer Research Campaign and the Imperial Cancer Research Fund. Its aim is to reduce the number of deaths from cancer. As the world's largest independent cancer...
's Beatson Institute of Cancer Research
Beatson Oncology Centre
The Beatson West of Scotland Cancer Centre is a specialised cancer care centre in Glasgow, Scotland. Until recently it had facilities in Gartnavel General Hospital, the Western Infirmary and Glasgow Royal Infirmary...
in Glasgow
Glasgow
Glasgow is the largest city in Scotland and third most populous in the United Kingdom. The city is situated on the River Clyde in the country's west central lowlands...
, UK, where she has overseen a £15 million expansion. She also leads the institute's Tumour Suppression research group.
Human papillomaviruses
Vousden's early work focused on the molecular biology of human papillomavirusHuman papillomavirus
Human papillomavirus is a member of the papillomavirus family of viruses that is capable of infecting humans. Like all papillomaviruses, HPVs establish productive infections only in keratinocytes of the skin or mucous membranes...
es (HPVs), which are associated with cervical cancer
Cervical cancer
Cervical cancer is malignant neoplasm of the cervix uteri or cervical area. One of the most common symptoms is abnormal vaginal bleeding, but in some cases there may be no obvious symptoms until the cancer is in its advanced stages...
. With Douglas Lowy and others, she pinpointed the specific viral oncoproteins required by HPV-16 to immortalise
Biological immortality
Biological immortality refers to a stable rate of mortality as a function of chronological age. Some individual cells and entire organisms in some species achieve this state either throughout their existence or after living long enough. This requires that death occur from injury or disease rather...
epithelial cells. She was also part of a group which showed that E6, one of the HPV-16 oncoproteins, binds to the human tumour suppressor protein p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
in vivo, resulting in its degradation.
p53
Vousden's recent research has centered on p53P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
. Sometimes called "the guardian of the genome", p53 plays a critical role in preventing the development of tumours by inducing cells subject to stress, such as DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
damage, to commit suicide via the apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
mechanism. Vousden's work has been important in delineating the mechanism of this process. With Katsunori Nakano, she discovered a key component in the apoptosis pathway triggered by p53, the protein PUMA
P53 upregulated modulator of apoptosis
The p53 upregulated modulator of apoptosis also known as Bcl-2-binding component 3 , is a pro-apoptotic protein, member of the Bcl-2 protein family. In humans, the Bcl-2-binding component 3 protein is encoded by the BBC3 gene....
(P53 Upregulated Modulator of Apoptosis).
Mdm2
Mdm2 is an important negative regulator of the p53 tumor suppressor. It is the name of a gene as well as the protein encoded by that gene. Mdm2 protein functions both as an E3 ubiquitin ligase that recognizes the N-terminal trans-activation domain of the p53 tumor suppressor and an inhibitor of...
. With Allan Weissman and others, she showed that Mdm2 is a ubiquitin ligase
Ubiquitin ligase
A ubiquitin ligase is a protein that in combination with an E2 ubiquitin-conjugating enzyme causes the attachment of ubiquitin to a lysine on a target protein via an isopeptide bond; the E3 ubiquitin ligase targets specific protein substrates for degradation by the proteasome...
which targets p53 for degradation by the proteasome
Proteasome
Proteasomes are very large protein complexes inside all eukaryotes and archaea, and in some bacteria. In eukaryotes, they are located in the nucleus and the cytoplasm. The main function of the proteasome is to degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks...
, thus ensuring levels of the protein remain low when the cell is not under stress.
Reactivating p53 can inhibit the growth of some tumours, making Mdm2 an attractive target for cancer therapeutics. As Mdm2 targets only a small number of proteins for destruction, an inhibitor might have few side effects. A major focus of Vousden's recent work has been investigating the structure of Mdm2 and seeking molecules that inhibit it; a group of low-molecular-weight compounds (discovered in collaboration with the Department of Chemistry at the University of Glasgow
University of Glasgow
The University of Glasgow is the fourth-oldest university in the English-speaking world and one of Scotland's four ancient universities. Located in Glasgow, the university was founded in 1451 and is presently one of seventeen British higher education institutions ranked amongst the top 100 of the...
) have recently shown promise in cell-culture studies. Mdm2 inhibitors have also been discovered by researchers at Hoffmann–La Roche and the Karolinska Institute
Karolinska Institutet
Karolinska institutet is a medical university in Solna within the Stockholm urban area, Sweden, and one of Europe's largest medical universities...
.
p53 can also help to prevent or repair minor damage to the genome under conditions of low stress. Vousden's group have recently discovered a novel p53-regulated protein, TIGAR
Tigar
Tigar is a 1978 drama film about retired boxing champion Sorga, nicknamed "Tigar". It is in the Serbo-Croatian language, and was made in Yugoslavia....
(T-p53 Inducible Glycolysis and Apoptosis Regulator), which can reduce oxidative stress
Oxidative stress
Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
in cells and might mediate part of this effect of p53.
Awards and honours
Vousden is a fellow of the Royal SocietyRoyal Society
The Royal Society of London for Improving Natural Knowledge, known simply as the Royal Society, is a learned society for science, and is possibly the oldest such society in existence. Founded in November 1660, it was granted a Royal Charter by King Charles II as the "Royal Society of London"...
(2003), Royal Society of Edinburgh
Royal Society of Edinburgh
The Royal Society of Edinburgh is Scotland's national academy of science and letters. It is a registered charity, operating on a wholly independent and non-party-political basis and providing public benefit throughout Scotland...
(2004) and the Academy of Medical Sciences
Academy of Medical Sciences
The Academy of Medical Sciences is the United Kingdom's national academy of medical sciences. It was established in 1998 on the recommendation of a group that was chaired by Michael Atiyah. Its president is John Irving Bell....
(2006); she was also elected a member of the European Molecular Biology Organization
European Molecular Biology Organization
EMBO stands for excellence in the life sciences. The EMBO mission is to enable the best science by supporting talented researchers, stimulating scientific exchange and advancing policies for a world-class European research environment....
in 2004. The Institute of Cancer Research
Institute of Cancer Research
The Institute of Cancer Research is a cancer research institute located in London, United Kingdom and a constituent college of the federal University of London. The ICR was founded in 1909 as a research department of the Royal Marsden Hospital and joined the University of London in 2003...
awarded her an Honorary Doctorate in Science (Medicine) in 2006. She will give the Sir Frederick Gowland Hopkins Memorial Lecture of the Biochemical Society
Biochemical Society
The Biochemical Society is a learned society in the United Kingdom in the field of biochemistry, including all the cellular and molecular biosciences.-Structure:...
in 2008.
In 2004, The Scotsman
The Scotsman
The Scotsman is a British newspaper, published in Edinburgh.As of August 2011 it had an audited circulation of 38,423, down from about 100,000 in the 1980s....
named Vousden among the 25 most powerful Scottish women.
Vousden was appointed Commander of the Order of the British Empire (CBE) in the 2010 New Year Honours.
Reviews and books
- Yee KS, Vousden KH. (2005) Complicating the complexity of p53 Carcinogenesis 26: 1317–1322 (PMID 15888490) (full-text pdf)
- Evan GI, Vousden KH. (2001) Proliferation, cell cycle and apoptosis in cancer Nature 411: 342–348 (PMID 11357141) (full-text pdf)
- Peters G, Vousden KH, eds. Oncogenes and Tumour Suppressors (Oxford University Press; 1997) (ISBN 0199635951)
Primary
- Wilson JM, Henderson G, Black F, et al.. (2007) Synthesis of 5-deazaflavin derivatives and their activation of p53 in cells Bioorg Med Chem 15: 77–86 (PMID 17064912)
- Bensaad K, Tsuruta A, Selak MA, et al.. (2006) TIGAR, a p53-inducible regulator of glycolysis and apoptosis Cell 126: 107–120 ( PMID 16839880)
- Nakano K, Vousden KH. (2001) PUMA, a novel proapoptotic gene, is induced by p53 Mol Cell 7: 683–694 ( PMID 11463392)
- Fang S, Jensen JP, Ludwig RL, et al.. (2000) Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53 J Biol Chem 275: 8945–8951 ( PMID 10722742) (full-text pdf)
- Kubbutat MHG, Jones SN, Vousden KH. (1997) Regulation of p53 stability by Mdm2 Nature 387: 299–303 (PMID 9153396)
- Hawley-Nelson P, Vousden KH, Hubbert NL et al.. (1989) HPV16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes EMBO J 8: 3905–3910 (PMID 2555178) (full-text pdf)