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Cambridge Immunology Network

 

Professor of Virus Genomics at Imperial College London and Vice President of infectious diseases & vaccines at Kymab Ltd, UK

Research

Paul Kellam is the Viral Genomics group leader and Senior Investigator at the Wellcome Trust Sanger Institute and a Professor of Viral Pathogenesis at UCL. Paul has a degree in Microbiology from Reading University and a PhD investigating HIV drug resistance from the Wellcome Foundation laboratories and Imperial College, London. At the Wellcome Foundation, Paul’s research on HIV identified essential reverse transcriptase (RT) mutations conferring drug resistance to zidovudine (AZT) leading to determining how the combinatorial development of multiple mutations leads to high-level resistance to antiviral drug regimes. This also led to the first use of capillary sequencing of HIV to detect minority drug resistance variants in patients. In 1996 Paul joined Robin Weiss’s laboratory at the Institute of Cancer Research to work on Kaposi’s sarcoma associated herpesvirus (KSHV). There Paul’s KSHV research identified the virus Latent Nuclear Antigen (LANA) and developed a monoclonal antibody to LANA that is marketed worldwide, being used for the identification of KSHV latently infected cells. This antibody was used to show definitively that KSHV is associated with all forms of Kaposi’s sarcoma, Primary Effusion Lymphoma (PEL) and a plasmablastic variant of Multicentric Castleman’s disease. Paul’s laboratory developed the first KSHV gene expression microarray to explore virus lytic replication and pioneered the use of virus bioinformatics and host gene expression arrays to characterise herpesvirus driven B-cell tumours. This identified the B-cell differentiation transcription factor, X-box binding protein-1 (XBP-1) as the host transcription factor that switches KSHV from latency to the virus lytic cycle. In 2009 Paul established the Virus Genomics laboratory at the Wellcome Trust Sanger Institute which investigates genetic variation of host and virus to determine the molecular and pathogenic outcomes of virus infections. In particular the laboratory uses next generation sequencing of virus and human genomes in people infected with HIV, influenza virus, norovirus, and human herpesviruses. Recently, we identified the first human influenza disease severity determining allele, IFITM3 in people hospitalised with pandemic influenza A H1N1. Paul’s laboratory combines molecular biology and virology with computational research to address basic biological questions in infection and immunity and has worked closely with the Kingdom of Saudi Arabia in characterising the genetics of MERS-CoV.

Publications

Key publications: 

Everitt AR,  Clare S, Pertel T, John SP, Wash RS, Smith SE, Chin CR, Feeley EM, Sims JS, Adams DJ, Wise HM, Kane L, Goulding DA, Digard P, Anttila V, Baillie JK, Walsh TS, Hume DA, Palotie A, Xue Y, Colonna V, Tyler-Smith C, Dunning J, Gordon S, The GenISIS Investigators, The MOSAIC Investigators, Smyth R, Openshaw P, Dougan G,. Brass AL, Kellam P. IFITM3 restricts the morbidity and mortality associated with influenza. Nature. 2012; 484:519-23. 

Watson SJ, Welkers MR, Depledge DP, Coulter E, Breuer JM, de Jong MD, Kellam P. Viral population analysis and minority-variant detection using short read next-generation sequencing. Philos Trans R Soc Lond B Biol Sci. 2013; 4;368(1614):20120205 

Bashford-Rogers, RJM, Palser, AL, Huntly BJ, Rance R, Vassiliou GS, Follows GA, Kellam P Network properties derived from deep sequencing of the human B-cell receptor repertoires delineates B-cell populations. Genome Research 2013; 23;11;1874-8 

Smith SE, Gibson MS, Wash RS, Ferrara F, Wright E, Temperton N, Kellam P and Fife, M. Chicken IFITM3 restricts Influenza viruses and Lyssaviruses in vitro. J.Virol 201387(23):12957-66. 

Everitt AR, Clare S, McDonald JU, Kane L, Harcourt K, Ahras M, Lall A, Hale C, Rodgers A, Young DB, Haque A, Billker O, Tregoning JS, Dougan G, Kellam P. Defining the range of pathogens susceptible to ifitm3 restriction using a knockout mouse model. PLoS One. 2013; 8(11): e80723

Lin TY, Chin CR, Everitt AR, Clare S, Perreira JM,  Savidis G, Aker AM, John SP, Sarlah D, Carreira EM, Elledge SJ, Kellam P, Brass AL­. Amphotericin B Increases Influenza A Virus Infection by Preventing IFITM3-mediated Restriction. Cell Reports 2013; 5(4), 895-908

 

Professor Paul  Kellam
Not available for consultancy

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