- Karen Vousden
Karen H. Vousden, 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 ofMdm2 , an attractive target for anti-cancer agents. She is currently the director ofCancer Research UK 's Beatson Institute of Cancer Research inGlasgow , UK.Education and career
Vousden gained a first degree in
genetics andmicrobiology (1978) and a PhD ingenetics (1982) from theUniversity of London . [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] (accessed 18 October 2007)] [http://www.nexxusscotland.com/documents/195 Nexxus: Professor Karen Vousden] (accessed 19 October 2007)] Her early post-doctoral positions were withChris Marshall at theInstitute of Cancer Research ,London ,UK (1981–5) andDouglas Lowy at theNational Cancer Institute ,Bethesda ,USA (1985–7). [http://science.cancerresearchuk.org/research/loc/glasgow/beatson/vousdenk/ Cancer Research UK: Karen Vousden] (accessed 18 October 2007)]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 inFrederick , 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 'sBeatson Institute of Cancer Research inGlasgow , UK, where she has overseen a £15 million expansion. [ [http://www.nature.com/nature/journal/v416/n6883/full/nj6883-99a.html NatureJobs: Cancer Research "Nature" 416: 99 (25 April 2002)] (accessed 18 October 2007)] [ [http://info.cancerresearchuk.org/images/publicationspdfs/regional_scotland.pdf Scotland Cancer Research UK 2007] (accessed 18 October 2007)] She also leads the institute's Tumour Suppression research group. [http://www.beatson.gla.ac.uk/research/?topic_id=36 The Beatson Institute for Cancer Research: Tumour Suppression - Karen Vousden] (accessed 18 October 2007)]Research
Human papillomaviruses
Vousden's early work focused on the molecular biology of
human papillomavirus es (HPVs), which are associated withcervical cancer . WithDouglas Lowy and others, she pinpointed the specific viraloncoprotein s required by HPV-16 to immortaliseepithelial cell s. [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] She was also part of a group which showed that E6, one of the HPV-16 oncoproteins, binds to the human tumour suppressor proteinp53 "in vivo", resulting in its degradation. [Lechner MS, Mack DH, Finicle AB, "et al". (1992) Human papillomavirus E6 proteins bind p53 "in vivo" and abrogate p53-mediated repression of transcription "EMBO J" 11: 3045–3052]p53
Vousden's recent research has centered on
p53 . 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 asDNA damage, to commit suicide via theapoptosis mechanism. Vousden's work has been important in delineating the mechanism of this process. WithKatsunori Nakano , she discovered a key component in the apoptosis pathway triggered by p53, the protein PUMA (P53 Upregulated Modulator of Apoptosis). [Nakano K, Vousden KH. (2001) PUMA, a novel proapoptotic gene, is induced by p53 "Mol Cell" 7: 683–694] [Yu J, Zhang L. (2003) No PUMA, no death: implications for p53-dependent apoptosis. "Cancer Cell" 4: 248-249]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 . WithAllan Weissman and others, she showed that Mdm2 is aubiquitin ligase which targets p53 for degradation by theproteasome , thus ensuring levels of the protein remain low when the cell is not under stress. [Kubbutat MHG, Jones SN, Vousden KH. (1997) Regulation of p53 stability by Mdm2 "Nature" 387: 299–303] [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]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. [http://jnci.oxfordjournals.org/cgi/reprint/97/3/166 Garber G. (2005) Missing the target: ubiquitin ligase drugs stall "J Natl Cancer Inst" 97: 166–167] (accessed 22 October 2007)] 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. [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] Mdm2 inhibitors have also been discovered by researchers atHoffmann–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 reduceoxidative stress in cells and might mediate part of this effect of p53. [Bensaad K, Tsuruta A, Selak MA, "et al". (2006) TIGAR, a p53-inducible regulator of glycolysis and apoptosis "Cell" 126: 107–120]Awards and honours
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