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After carrying out postdoctoral work at universities in Bern, Switzerland, Edinburgh, and Sussex, he joined the Imperial Cancer Research Fund (ICRF) in London in 1984. After some time in Oxford as Chair of the Department of Microbiology, he was appointed Chief Executive of Cancer Research UK in 2002. He moved his laboratory to the United States upon being named President of Rockefeller University in 2003 and was also Director of the Anderson Center for Cancer Research at Rockefeller. He is a member of the Royal Society and a Foreign Associate of the US National Academy of Sciences. In 1999 he received a knighthood for services in cancer research and cell biology and since 2000 has been a member of CST advising the Prime Minister on science and technology. He received The Royal Society's Royal and Copley Medals and the Legion of Honor in 2002 and the Nobel Prize in Physiology or Medicine in 2001.
Sir Paul stepped down as President of Rockefeller University in December 2010 to return to the UK as Head of the new UK Centre for Medical Research and Innovation in London, and as President of the Royal Society, following Sir Martin Rees on 30 November 2010.