Karen Vousden

{{Infobox scientist

| name = Karen Vousden

| honorific_suffix = {{postnominals|country=GBR|size=100%|CBE|FRS|FRSE|FMedSci}}

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| birth_date = {{Birth date and age|df=yes|1957|07|19}}{{Who's Who | title=Vousden, Prof. Karen Heather, (Mrs R. Ludwig) | id = U44064 | volume = 2016 | edition = online Oxford University Press|location=Oxford}}

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| fields = Cancer{{Cite journal

| last1 = Evan | first1 = Gerard I.

| authorlink1 = Gerard Evan

| last2 = Vousden | first2 = Karen H.

| authorlink2 = Karen Vousden

| title = Proliferation, cell cycle and apoptosis in cancer

| journal = Nature

| volume = 411

| issue = 6835

| pages = 342–348

| doi = 10.1038/35077213

| year = 2001

| pmid = 11357141

| bibcode = 2001Natur.411..342E

| s2cid = 4414024

}}Peters G, Vousden KH, eds. Oncogenes and Tumour Suppressors (Oxford University Press; 1997) ({{ISBN|0199635951}})

| workplaces = {{Plainlist|

| alma_mater = Queen Mary and Westfield College

| thesis_title = Use of suppressor gene mutations to study transfer RNA redundancy in Coprinus

| thesis_url = https://www.proquest.com/docview/301407293

| thesis_year = 1982

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| known_for = Work on p53 tumour suppressor protein{{Cite journal

| last1 = Sedwick | first1 = C.

| title = Karen Vousden: Getting the big picture on p53

| doi = 10.1083/jcb.1982pi

| journal = The Journal of Cell Biology

| volume = 198

| issue = 2

| pages = 148–149

| year = 2012

| pmid = 22826118

| pmc =3410416

}}{{Cite journal

| last1 = Yee | first1 = K. S.

| last2 = Vousden | first2 = K. H.

| title = Complicating the complexity of p53

| doi = 10.1093/carcin/bgi122

| journal = Carcinogenesis

| volume = 26

| issue = 8

| pages = 1317–1322

| year = 2005

| pmid = 15888490

| doi-access = free

}} and Mdm2 protein

| influences =

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| awards = {{Plainlist|

CBE (2010)
FRS (2003)
EMBO Member (2004)
FRSE (2004)
FMedSci{{when|date=November 2016}}}}

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| spouse = {{marriage|Robert Ludwig|1986}}

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}}

Karen Heather Vousden (born 19 July 1957) 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. From 2003 to 2016, she was the director of the Cancer Research UK Beatson Institute in Glasgow, UK, moving back to London in 2016 to take up the role of Chief Scientist at CRUK and Group Leader at the Francis Crick Institute.

Education

After attending Gravesend Grammar School for Girls,{{citation needed|date=January 2013}} Vousden gained a Bachelor of Science degree in genetics and microbiology (1978) and a PhD from Queen Mary College, University of London on the use of suppressor gene mutations to study transfer RNA redundancy in the fungus Coprinus.[http://www.cancerschool.gla.ac.uk/reports/dr-karen-vousden-20-03-02.html University of Glasgow School for Cancer Studies: Dr. Karen H. Vousden] {{Webarchive|url=https://web.archive.org/web/20070206150926/http://www.cancerschool.gla.ac.uk/reports/dr-karen-vousden-20-03-02.html |date=6 February 2007 }} (accessed 18 October 2007)[http://www.nexxusscotland.com/documents/195 Nexxus: Professor Karen Vousden] (accessed 19 October 2007) {{webarchive |url=https://web.archive.org/web/20110714180053/http://www.nexxusscotland.com/documents/195 |date=14 July 2011 }}{{cite thesis |degree=PhD |first=Karen|last=Vousden |title=Use of suppressor gene mutations to study transfer RNA redundancy in Coprinus |publisher=Queen Mary and Westfield College |year=1982 |authorlink=Karen Vousden|oclc=940246473|id={{ProQuest|301407293}}}}{{subscription required}}

Career

Vousden's early postdoctoral research positions were with Chris Marshall{{Cite journal

| last1 = Vousden | first1 = K. H.

| last2 = Marshall | first2 = C. J.

| title = Three different activated ras genes in mouse tumours; evidence for oncogene activation during progression of a mouse lymphoma

| journal = The EMBO Journal

| volume = 3

| issue = 4

| pages = 913–917

| year = 1984

| pmid = 6327295

| pmc = 557447

| doi = 10.1002/j.1460-2075.1984.tb01905.x

}} at the Institute of Cancer Research, London, UK (1981–85) and Douglas Lowy{{Cite journal

| last1 = Schiller | first1 = J. T.

| last2 = Vass | first2 = W. C.

| last3 = Vousden | first3 = K. H.

| last4 = Lowy | first4 = D. R.

| title = E5 open reading frame of bovine papillomavirus type 1 encodes a transforming gene

| journal = Journal of Virology

| volume = 57

| issue = 1

| pages = 1–6

| year = 1986

| pmid = 3001335

| pmc = 252691

| doi = 10.1128/JVI.57.1.1-6.1986

}} at the National Cancer Institute, Bethesda, United States (1985–87).[http://science.cancerresearchuk.org/research/loc/glasgow/beatson/vousdenk/ Cancer Research UK: Karen Vousden] (accessed 18 October 2007) {{webarchive |url=https://web.archive.org/web/20060928025337/http://science.cancerresearchuk.org/research/loc/glasgow/beatson/vousdenk/ |date=28 September 2006 }}

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 (1995–97), director of the Molecular Virology and Carcinogenesis Laboratory (1997–98), interim director of the ABL-Basic Research Program (1998–99) and chief of the Regulation of Cell Growth Laboratory, Division of Basic Sciences (1999–2002).

From 2003 to 2016, she was the director of the Cancer Research UK Beatson Institute in Glasgow, UK, where she oversaw a £15 million expansion.{{Cite journal | author = Anon| title = Nature jobs changes| journal = Nature | volume = 417 | issue = 6887 | pages = 99 | year = 2002 | doi = 10.1038/nj6883-99a | doi-access = free }}[http://info.cancerresearchuk.org/images/publicationspdfs/regional_scotland.pdf Scotland Cancer Research UK 2007] (accessed 18 October 2007){{dead link|date=June 2013}} She also led the institute's Tumour Suppression research group.[http://www.beatson.gla.ac.uk/cancer-metabolism-growth-and-survival/karen-vousden-tumour-suppression.html Cancer Research UK Beatson Institute: Karen Vousden – Tumour Suppression] {{Webarchive|url=https://web.archive.org/web/20150713175711/http://www.beatson.gla.ac.uk/cancer-metabolism-growth-and-survival/karen-vousden-tumour-suppression.html |date=13 July 2015 }} (accessed 18 October 2007) She also served on the Life Sciences jury for the Infosys Prize in 2014.

Since 2016, she has moved back to London to take up the role of CRUK Chief Scientist and Group Leader at the Francis Crick Institute.[https://www.crick.ac.uk/research/a-z-researchers/researchers-v-y/karen-vousden/biography/ Francis Crick Institute: Karen Vousden Biography] In 2018, she was elected a foreign associate of the National Academy of Sciences.

Research

=Human papillomaviruses=

Vousden's early work focused on the molecular biology of human papillomaviruses (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.{{Cite journal

| last1 = Hawley-Nelson | first1 = P.

| last2 = Vousden | first2 = K. H.

| last3 = Hubbert | first3 = N. L.

| last4 = Lowy | first4 = D. R.

| last5 = Schiller | first5 = J. T.

| title = HPV16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes

| journal = The EMBO Journal

| volume = 8

| issue = 12

| pages = 3905–3910

| year = 1989

| pmid = 2555178

| pmc = 402081

| doi = 10.1002/j.1460-2075.1989.tb08570.x

}} 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.{{Cite journal

| last1 = Lechner | first1 = M. S.

| last2 = Mack | first2 = D. H.

| last3 = Finicle | first3 = A. B.

| last4 = Crook | first4 = T.

| last5 = Vousden | first5 = K. H.

| last6 = Laimins | first6 = L. A.

| title = Human papillomavirus E6 proteins bind p53 in vivo and abrogate p53-mediated repression of transcription

| journal = The EMBO Journal

| volume = 11

| issue = 8

| pages = 3045–3052

| year = 1992

| pmid = 1379175

| pmc = 556787

| doi = 10.1002/j.1460-2075.1992.tb05375.x

}}

=p53 suppressor protein=

Vousden's recent research has centred on p53, a gene which 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. Her 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).{{Cite journal

| last1 = Nakano | first1 = K.

| last2 = Vousden | first2 = K. H.

| doi = 10.1016/S1097-2765(01)00214-3

| title = PUMA, a Novel Proapoptotic Gene, is Induced by p53

| journal = Molecular Cell

| volume = 7

| issue = 3

| pages = 683–694

| year = 2001

| pmid = 11463392

| doi-access = free

}}{{Cite journal

| doi = 10.1016/S1535-6108(03)00249-6

| last1 = Yu | first1 = J.

| last2 = Zhang | first2 = L.

| title = No PUMA, no death: Implications for p53-dependent apoptosis

| journal = Cancer Cell

| volume = 4

| issue = 4

| pages = 248–249

| year = 2003

| pmid = 14585351

| url = https://zenodo.org/record/895373

| doi-access = free

}}

Image:Mdm2.png

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.{{Cite journal

| last1 = Fang | first1 = S.

| last2 = Jensen | first2 = J. P.

| last3 = Ludwig | first3 = R. L.

| last4 = Vousden | first4 = K. H.

| last5 = Weissman | first5 = A. M.

| title = Mdm2 is a RING Finger-dependent Ubiquitin Protein Ligase for Itself and p53

| doi = 10.1074/jbc.275.12.8945

| journal = Journal of Biological Chemistry

| volume = 275

| issue = 12

| pages = 8945–8951

| year = 2000

| pmid = 10722742

| doi-access = free

}}{{Cite journal

| last1 = Kubbutat | first1 = M. H. G.

| last2 = Jones | first2 = S. N.

| last3 = Vousden | first3 = K. H.

| doi = 10.1038/387299a0

| title = Regulation of p53 stability by Mdm2

| journal = Nature

| volume = 387

| issue = 6630

| pages = 299–303

| year = 1997

| pmid = 9153396

| bibcode = 1997Natur.387..299K

| s2cid = 4329670

}}

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.{{Cite journal | last1 = Garber | first1 = K. | title = Missing the Target: Ubiquitin Ligase Drugs Stall | doi = 10.1093/jnci/97.3.166 | pmid = 15687356 | journal = JNCI Journal of the National Cancer Institute | volume = 97 | issue = 3 | pages = 166–167 | year = 2005 | doi-access = free }} 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.{{Cite journal

| last1 = Wilson | first1 = J. M.

| last2 = Henderson | first2 = G.

| last3 = Black | first3 = F.

| last4 = Sutherland | first4 = A.

| last5 = Ludwig | first5 = R. L.

| last6 = Vousden | first6 = K. H.

| last7 = Robins | first7 = D. J.

| doi = 10.1016/j.bmc.2006.10.011

| title = Synthesis of 5-deazaflavin derivatives and their activation of p53 in cells

| journal = Bioorganic & Medicinal Chemistry

| volume = 15

| issue = 1

| pages = 77–86

| year = 2007

| pmid = 17064912

}} 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.{{Cite journal

| last1 = Bensaad | first1 = K.

| last2 = Tsuruta | first2 = A.

| last3 = Selak | first3 = M. A.

| last4 = Vidal | first4 = M. N. C.

| last5 = Nakano | first5 = K.

| last6 = Bartrons | first6 = R.

| last7 = Gottlieb | first7 = E.

| last8 = Vousden | first8 = K. H.

| doi = 10.1016/j.cell.2006.05.036

| title = TIGAR, a p53-Inducible Regulator of Glycolysis and Apoptosis

| journal = Cell

| volume = 126

| issue = 1

| pages = 107–120

| year = 2006

| pmid = 16839880

| s2cid = 15006256

| doi-access = free

}}

=Key publications=

{{cite journal | last1 = Yee | first1 = KS | last2 = Vousden | first2 = KH | year = 2005 | title = Complicating the complexity of p53 | journal = Carcinogenesis | volume = 26 | issue = 8 | pages = 1317–1322 | pmid = 15888490 | doi=10.1093/carcin/bgi122| doi-access = free }}
{{cite journal | last1 = Evan | first1 = GI | last2 = Vousden | first2 = KH | year = 2001 | title = Proliferation, cell cycle and apoptosis in cancer | journal = Nature | volume = 411 | issue = 6835 | pages = 342–348 | pmid = 11357141 | doi=10.1038/35077213 | bibcode = 2001Natur.411..342E | s2cid = 4414024 | url = http://minf.vub.ac.be/~chrisvs/PapersMCD7.pdf }}
Peters G, Vousden KH, eds. Oncogenes and Tumour Suppressors (Oxford University Press; 1997) ({{ISBN|0199635951}})
{{cite journal | last1 = Wilson | first1 = JM | last2 = Henderson | first2 = G | last3 = Black | first3 = F | display-authors = etal | title = . (2007) Synthesis of 5-deazaflavin derivatives and their activation of p53 in cells | journal = Bioorg Med Chem | volume = 15 | pages = 77–86 | pmid = 17064912 | doi=10.1016/j.bmc.2006.10.011 | date=January 2007| issue = 1 }}
{{cite journal | last1 = Bensaad | first1 = K | last2 = Tsuruta | first2 = A | last3 = Selak | first3 = MA | display-authors = etal | year = 2006 | title = TIGAR, a p53-inducible regulator of glycolysis and apoptosis | journal = Cell | volume = 126 | issue = 1 | pages = 107–120 | doi = 10.1016/j.cell.2006.05.036 | pmid = 16839880 | s2cid = 15006256 | doi-access = free }}
{{cite journal | last1 = Nakano | first1 = K | last2 = Vousden | first2 = KH | year = 2001 | title = PUMA, a novel proapoptotic gene, is induced by p53 | journal = Mol Cell | volume = 7 | issue = 3 | pages = 683–694 | doi = 10.1016/S1097-2765(01)00214-3 | pmid = 11463392 | doi-access = free }}
{{cite journal | last1 = Fang | first1 = S | last2 = Jensen | first2 = JP | last3 = Ludwig | first3 = RL | display-authors = etal | year = 2000 | title = Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53 | journal = J Biol Chem | volume = 275 | issue = 12 | pages = 8945–8951 | doi = 10.1074/jbc.275.12.8945 | pmid=10722742| doi-access = free }}
{{cite journal | last1 = Kubbutat | first1 = MHG | last2 = Jones | first2 = SN | last3 = Vousden | first3 = KH | year = 1997 | title = Regulation of p53 stability by Mdm2 | journal = Nature | volume = 387 | issue = 6630 | pages = 299–303 | pmid = 9153396 | doi=10.1038/387299a0| bibcode = 1997Natur.387..299K | s2cid = 4329670 }}
{{cite journal | last1 = Hawley-Nelson | first1 = P | last2 = Vousden | first2 = KH | last3 = Hubbert | first3 = NL | display-authors = etal | year = 1989 | title = HPV16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes | journal = EMBO J | volume = 8 | issue = 12 | pages = 3905–3910 | pmid = 2555178 | pmc=402081| doi = 10.1002/j.1460-2075.1989.tb08570.x }}

Awards and honours

Vousden is a fellow of the Royal Society (2003),[http://www.royalsoc.ac.uk/page.asp?id=1564 Royal Society: Professor Karen Vousden FRS – Cancer’s achilles heel?] (accessed 18 October 2007) {{webarchive |url=https://web.archive.org/web/20071013024411/http://www.royalsoc.ac.uk/page.asp?id=1564 |date=13 October 2007 }} Royal Society of Edinburgh (2004)[http://www.royalsoced.org.uk/fellowship/elections/elect04.htm Royal Society of Edinburgh: Election of Fellows 2004] {{Webarchive|url=https://web.archive.org/web/20070923061019/http://www.royalsoced.org.uk/fellowship/elections/elect04.htm |date=23 September 2007 }} (accessed 19 October 2007) and the Academy of Medical Sciences (2006);[http://www.acmedsci.ac.uk/p121fid846.html Academy of Medical Sciences: Professor Karen Vousden FRS FMedSci] {{webarchive|url=https://web.archive.org/web/20110719004115/http://www.acmedsci.ac.uk/p121fid846.html |date=19 July 2011 }} (accessed 18 October 2007) she was also elected a member of the European Molecular Biology Organization in 2004.[http://www.embo.org/publications/annual_report_04.pdf EMBO EMBC Annual Report 2004] (accessed 19 October 2007) {{webarchive |url=https://web.archive.org/web/20060831051820/http://www.embo.org/publications/annual_report_04.pdf |date=31 August 2006 }} The Institute of Cancer Research awarded her an Honorary Doctorate in Science (Medicine) in 2006.[http://www.icr.ac.uk/about_us/annual_research_report/annual_research_report_2006/7508.pdf Institute of Cancer Research: Academic Dean's Report 2006] {{webarchive|url=https://web.archive.org/web/20110611002347/http://www.icr.ac.uk/about_us/annual_research_report/annual_research_report_2006/7508.pdf |date=11 June 2011 }} (accessed 18 October 2007) She gave the Sir Frederick Gowland Hopkins Memorial Lecture of the Biochemical Society in 2008.[http://www.biochemist.org/bio/02905/0050/029050050.pdf Biochemical Society Awards in 2008, The Biochemist October 2007, p. 50] (accessed 18 October 2007) She was awarded the Royal Medal from the Royal Society of Edinburgh in 2009. Vousden was appointed Commander of the Order of the British Empire (CBE) in the 2010 New Year Honours.{{London Gazette |issue=59282 |date=31 December 2009 |page=8 |supp=y }}

In 2004, The Scotsman named Vousden among the 25 most powerful Scottish women.[http://news.scotsman.com/topics.cfm?tid=288&id=1019042004 Bowditch G. Scotland's top 50 powerful women, The Scotsman (31 August 2004)] (accessed 18 October 2007)

In 2021, Karen Vousden was recognized with the first [https://www.pezcoller.it/en/awards/the-pezcoller-%E2%80%93-marina-larcher-fogazzaro-%E2%80%93-eacr-women-in-cancer-research-award-/ Pezcoller Foundation-Marina Larcher Fogazzaro-EACR Women in Cancer Award].