Karen Heather Vousden (born 19 July 1957)[4] 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.
From 1987 to 1995, she led the Human Papillomavirus Group at the Ludwig Institute for Cancer Research, London, UK.[8][14] In 1995, she joined the National Cancer Institute in Frederick, USA,[14] 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).[8][10]
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.[14][15][16] She also led the institute's Tumour Suppression research group.[17] 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.[18] In 2018, she was elected a foreign associate of the National Academy of Sciences.
Vousden's recent research has centred on p53,[21] 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).[22][23]
Structure of Mdm2
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.[7][24][25]
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.[24] 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.[24][26] Mdm2 inhibitors have also been discovered by researchers at Hoffmann–La Roche and the Karolinska Institute.[24]
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.[27]
Peters G, Vousden KH, eds. Oncogenes and Tumour Suppressors (Oxford University Press; 1997) (ISBN0199635951)
Wilson, JM; Henderson, G; Black, F; et al. (January 2007). ". (2007) Synthesis of 5-deazaflavin derivatives and their activation of p53 in cells". Bioorg Med Chem. 15 (1): 77–86. doi:10.1016/j.bmc.2006.10.011. PMID17064912.
^Vousden, Karen (1982). Use of suppressor gene mutations to study transfer RNA redundancy in Coprinus (PhD thesis). Queen Mary and Westfield College. OCLC940246473. ProQuest301407293.(subscription required)
^Wilson, J. M.; Henderson, G.; Black, F.; Sutherland, A.; Ludwig, R. L.; Vousden, K. H.; Robins, D. J. (2007). "Synthesis of 5-deazaflavin derivatives and their activation of p53 in cells". Bioorganic & Medicinal Chemistry. 15 (1): 77–86. doi:10.1016/j.bmc.2006.10.011. PMID17064912.
