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Title: Senior Investigator
Work: Wellcome Trust Sanger Institute, Cambridge, United Kingdom
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’s career has spanned the pharmaceutical company and academic research. At the Wellcome Foundation Ltd, Paul’s research on HIV-1 drug resistance identified one of the essential reverse transcriptase (RT) mutations conferring resistance to zidovudine (AZT) and this identified how the development of multiple mutations lead to high-level resistance to antiviral drug regimes. Paul’s work also showed the stepwise accumulation of AZT resistance mutants in patients and determined that retroviral recombination resulted in the genetic linkage of mutations conferring high-level drug resistance. Importantly, this work contributed directly to the adoption of DNA sequencing to support HIV-1 drug therapy choices and to a novel HIV-1 phenotyping assay commercialised by Tibotec-Virco (Antivirogram) and ViroLogic (PhenoSense).
In 1996 Paul joined Robin Weiss’s laboratory as a Cancer Research Campaign Fellow, to work on Kaposi’s sarcoma associated herpesvirus (KSHV). Paul’s KSHV research identified the virus Latent Nuclear Antigen (LANA) and developed a monoclonal antibody to LANA that is used for the identification of KSHV latently infected cells. This antibody was used to show 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 KSHV 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 to investigate genetic variation of host and virus in infectious diseases. Paul’s laboratory identified the first influenza disease severity determining allele, in the human gene IFITM3 in people hospitalised with pandemic influenza A H1N1. This work has been rapidly replicated by others throughout the world and stands as the only example of a characterised human gene polymorphism affecting the clinical outcome to infection by influenza. Paul’s laboratory produced the majority of the initial genome analysis of the Middle East Respiratory Syndrome Coronavirus (MERS CoV) outbreaks in Saudi Arabia where the analysis showed that the transmission pattern of MERS CoV was consistent with multiple transfer events from an animal reservoir and contributing to the identification of MERS CoV in camels. Paul has published 150 papers and reviews and his work has been cited over 9000 times.