Dr Andrew Hislop

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Dr Andrew Hislop is a viral immunologist with an interest in how T-cells control oncogenic human viruses such as Kaposi sarcoma-associated herpesvirus, Epstein-Barr virus and Merkel cell virus.
Position:

Senior Research Fellow, School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham. 

Email: a.d.hislop@bham.ac.uk

UoB profile

Background and Research focus

Dr Andrew Hislop and his team are studying the T-cell immune response to oncogenic human viruses. The viruses that they are focussing on include Epstein-Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV), and Merkel cell polyomavirus. EBV-derived antigens could potentially provide viable T-cell targets, yet initial studies from the Hislop group reveal that only a fraction of these antigens are targeted by T-cells. Hence, his lab are conducting comprehensive surveys for immune targets in the entire Epstein-Barr virus proteome to further understand how these viral-derived antigens are selected and targeted by the immune system. Andrew and his team are also interested in defining the immune evasion mechanisms implemented by KSHV. Strikingly, some of the latent proteins demonstrate features which may reduce efficient targeting by CD8+ T-cells. With this in mind, his group is examining the efficiency with which KSHV-specific CD8+ T-cells recognise these antigens, if these mechanisms can be overcome and whether other immune effectors such as CD4+ T-cells are sensitive to these evasion mechanisms. Related to this, they have recently found that KSHV-transformed cells are insensitive to KSHV-specific CD4+ T-cell mediated killing. They are examining whether viral derived anti-apoptotic proteins are responsible for impeding eradication by CD4+ T-cells. Moreover, they are using chemical inhibitors to disrupt key signalling pathways essential for preventing apoptosis, with the eventual aim of restoring sensitivity of KSHV-derived malignant cells to T-cell mediated killing. Latterly, Andrew and his group have broadened their research focus to study Merkel cell polyomavirus, a recently discovered virus which has been linked with the development of Merkel cell carcinoma. Andrew’s group is currently isolating T lymphocytes specific to these Merkel cell polyomavirus antigens to assess whether these will recognise Merkel cell carcinoma cells and whether these can be used therapeutically to eradicate disease caused by this virus.

Expertise

Tumour Immunology; EBV associated malignancies; Kaposi sarcoma associated herpesvirus; antigen processing and presentation; Merkel cell poyomavirus; Merkel cell carcinoma.

Other activities

Andrew has received funding from the Medical Research Council (MRC) and the Association of International Cancer Research (AICR). In addition to his research, Andrew makes substantial contributions to teaching at many levels. In particular, he co-ordinates and delivers lectures on a range of undergraduate (BMedSc and MBChB) and postgraduate (MSc in Immunology and Immunotherapy and Mres in Molecular and Cellular Medicine) courses. He is also closely affiliated with the Cancer Immunology and Immunotherapy Centre (CIIC). Finally he serves as a peer reviewer for a number of research bodies and scientific journals. 

Publications

Sabbah S, Jagne YJ, Zuo J, de Silva T, Ahasan MM, Brander C, Rowland-Jones S, Flanagan KL, Hislop AD. 2012. T-cell immunity to Kaposi’s sarcoma-associated herpesvirus: recognition of primary effusion lymphoma with LANA-specific CD4+ T cells. Blood. 119:2083-92.

Misstear K, Chanas SA, Rezaee SA, Colman R, Quinn LL, Long HM, Goodyear O, Lord JM, Hislop AD, Blackbourn DJ. 2012. Suppression of Antigen-Specific T Cell Responses by the Kaposi’s Sarcoma-Associated Herpesvirus Viral OX2 Protein and Its Cellular Orthologue, CD200. J Virol. 86:6246-57.

Jayasooriya S, Hislop A, Peng Y, Croom-Carter D, Jankey Y, Bell A, Dong T, Rowland-Jones S, Rickinson A, Walther M, Whittle H. 2012. Revisiting the effect of acute P. falciparum malaria on Epstein-Barr virus: host balance in the setting of reduced malaria endemicity. PLoS One 7:331142.

Zuo J, Thomas WA, Haigh TA, Fitzsimmons L, Long HM, Hislop AD, Taylor GS, Rowe M. 2011. Epstein-Barr Virus Evades CD4 T Cell Responses in Lytic Cycle through BZLF1-mediated Downregulation of CD74 and the Cooperation of vBcl-2. PLoS Pathog. e1002455.

Palendira U, Low C, Chan A, Hislop AD, Ho E, Phan TG, Deenick E, Cook MC, Riminton DS, Choo S, Loh R, Alvaro F, Booth C, Gaspar HB, Moretta A, Khanna R, Rickinson AB, Tangye SG. 2011. Molecular pathogenesis of EBV susceptibility in XLP as revealed by analysis of female carriers with heterozygous expression of SAP. PLoS Biol. e1001187.

Zuo J, Quinn LL, Tamblyn J, Thomas WA, Feederle R, Delecluse HJ, Hislop AD, Rowe M. 2011. The Epstein-Barr virus-encoded BILF1 protein modulates immune recognition of endogenously processed antigen by targeting major histocompatibility complex class I molecules trafficking on both the exocytic and endocytic pathways. Journal of Virology 85:1604-14.

Hislop AD, Palendira U, Leese AM, Arkwright PD, Rohrlich PS, Tangye SG, Gaspar HB, Lankester AC, Moretta A, Rickinson AB. 2010. Impaired Epstein-Barr virus-specific CD8+ T cell function in X-linked lymphoproliferative disease is restricted to SLAM family positive B cell targets. Blood 116:3249-3257.

Croft NP, Shannon-Lowe C, Bell AI, Horst D, Kremmer E, Ressing ME, Wiertz EJ, Middeldorp JM, Rowe M, Rickinson AB, Hislop AD. 2009. Stage-specific inhibition of MHC class I presentation by the Epstein-Barr virus BNLF2a protein during virus lytic cycle. PLoS Pathogens. 5: e1000490.