Research
Over the last 20 years I have been studying the herpesvirus Human Cytomegalovirus (HCMV) in the Department of Medicine in the group of John Sinclair. Specifically I have been investigating the molecular mechanism of a phase of the lifecycle termed ‘latency’ whereby undifferentiated cells are infected, but non-productively, until the cells are terminally differentiated. To address this I used a multi-omics approach (transcriptomics, proteomics etc) to identify virally induced cellular changes. We have since applied these findings to designing potential therapeutics which may be used to treat human tissue (stem cells and organs) prior to transplantation.
On the 1st November 2023 I will be commencing an independent position in the Department of Pathology. In this post I intend to continue these lines of research and I am also interested in understanding HCMV in other clinical settings, such as placental transfer to the newborn where it causes significant disease and is a significant burden to the NHS.
Publications
The Human Cytomegalovirus Latency-Associated Gene Product Latency UniqueNatural Antigen Regulates Latent Gene Expression’. Poole, E.; Lau, J.; Groves, I.;Roche, K.; Murphy, E.;Carlan da Silva, M.; Reeves, M.;Sinclair, J. Viruses (2023),15,1875. https://doi.org/10.3390/v15091875
‘Latency-associated upregulation of SERBP1 is important for the recruitment of transcriptional repressors to the viral major immediate early promoter of human cytomegalovirus during latent carriage’ E. Poole and J. Sinclair Frontiers in Microbiology (2022) doi: 10.3389/fmicb.2022.999290
'A BMPR2/YY1 signalling axis is required for HCMV latency in undifferentiated myeloid cells.' Poole, E*., Carlan da Silva, M., Huang, C., Groves, I., Perera, M., Jackson, S., Wills, M., Rana, M. and Sinclair J. (2021) mBio https://doi.org/10.1128/mBio.00227-21
'Bromodomain proteins regulate human cytomegalovirus latency and reactivation allowing epigenetic therapeutic intervention' Groves, I., Jackson, S., Poole, E., Nachson, A., Rozman, B., Schwartz, M., Prinjha,R., Tough, D., Sinclair J. and Wills, M. PNAS March 2, (2021) 118 (9) e2023025118; https://doi.org/10.1073/pnas.2023025118
‘Understanding HCMV Latency Using Unbiased Proteomic Analyses’ Poole E. and Sinclair J. Pathogens 2020, 9(7), 590; doi:10.3390/pathogens9070590
'A virally encoded de-sumoylase is required for reactivation from latency' Poole. E., Lau, J., Kew, V., Sinclair, J., and Reeves, M. Cell Rep, 2018 Jul 17;24(3):594-606. doi: 10.1016/j.celrep.2018.06.048.
'Targeting the latent cytomegalovirus reservoir with an antiviral fusion toxin protein.' Krishna BA, Spiess K, Poole EL, Lau B, Voigt S, Kledal TN, Rosenkilde MM, Sinclair JH. Nature Commun. (2017) Feb 2;8:14321. doi: 10.1038/ncomms14321.
'Transient activation of human cytomegalovirus lytic gene expression during latency allows cytotoxic T cell killing of latently infected cells.' Krishna BA, Lau B, Jackson SE, Wills MR, Sinclair JH, Poole E*. Nature Sci Rep. (2016) Apr 19;6:24674. doi: 10.1038/srep24674.PMID:27091512
'The human cytomegalovirus non-coding Beta2.7 RNA as a novel therapeutic for Parkinson's disease - translational research with no translation.' Poole, E., Kuan, W., Barker, R., and Sinclair, J. Virus Res. (2016) Jan 2;212:64-9. doi: 10.1016/j.virusres.2015.05.007. Epub 2015 May 21.PMID: 26003955
'Alveolar macrophages isolated directly from HCMV seropositive individuals are sites of HCMV reactivation in vivo' Poole, E., Jatinder, J., Krishna, B., Herre, J., Chilvers, E., and Sinclair, J. J. Infect. Dis. (2015) Jun 15;211(12):1936-42. doi: 10.1093/infdis/jiu837
“Latency-associated degradation of the MRP1 drug transporter during latent human cytomegalovirus infection.” Weekes, M., Tan SY, Poole E., Talbot S, Antrobus R, Smith DL, Montag C, Gygi SP, Sinclair JH, Lehner PJ. Science (2013) Apr 12;340(6129):199-202. doi: 10.1126/science.1235047
“A novel neuroprotective therapy for Parkinson’s disease using a viral non-coding RNA that protects mitochondrial complex I activity” Kuan, W-L., Poole, E., Fletcher, M., Tyers, P., Wills, M., Barker, R. and Sinclair, J. Journal of Experimental Medicine (2012), 209 1-10.
