David J. Blackbourn is Professor and Head of the School of Biosciences and Medicine, Faculty of Health and Medical Sciences. His group studies viruses that are responsible for causing cancer. In particular, his interests lie in how such viruses cause disease, evade the immune response and interact with the DNA damage response.
Prof Blackbourn has published over 70 research papers and reviews in virology and immunology. He has received major grant funding from Cancer Research UK, The Wellcome Trust, the MRC, BBSRC and the Royal Society. He is a Fellow of the Society of Biology (FSB).
Infectious agents, including viruses, are associated with up to 20% of human cancers. The Blackbourn laboratory studies two such viruses: Kaposi's sarcoma-associated herpesvirus (KSHV) and Merkel cell polyomavirus (MCV or MCPyV).
Our major interest is in how viruses cause disease and modulate the immune response. KSHV provides a model for most of our studies, but the impact of our work could extend to other viruses or host/pathogen interactions. Our main research topics in this context are:
- How KSHV interacts with the DNA damage response.
- How KSHV modulates the type I interferon (alpha & beta) response.
- How KSHV deregulates antigen-specifc T cell responses.
- What are the consequences of KSHV infection on endothelial cell biology, including cell-cell interactions and regulating leukocyte recruitment.
For MCV, our interests lie in understanding the tumour microenvironment and how it contributes to the pathogenesis of Merkel cell carcinoma.
Prof Blackbourn collaborates with colleagues throughout the world, including:
- Dr Roger Grand, University of Birmingham
- Dr Andrew Hislop, University of Birmingham
- Professor Christian Munz, University of Zurich
- Dr Mohamed Mutocheluh, Kwame Nkrumah University of Science and Technology (KNUST), Ghana
- Dr Neil Steven, University of Birmingham
- Professor Rolf Renne, University of Florida
Publications from the last five years:
McKimmie, C.S., M.D. Singh, K. Hewit, O. Franco-Lopez, M. Le Broq, S. Rose-John, A.H. Baker, R. Wheat, D.J. Blackbourn, R.J.B. Nibbs and G.J. Graham. An analysis of the function and expression of D6 on lymphatic endothelial cells. Blood, 121: 3768-3777. 2013
Jacobs, S.R., S.M. Gregory, J.A. West, A.C. Wollish, D.J. Blackbourn, M.T. Heise and B. Damania. The KSHV vIRFs inhibit interferon activation mediated by TLR3. J. Virol. 87: 798-806, 2013.
Damania, B and D.J. Blackbourn. Innate Barriers to Viral Infection. Future Microbiology 7:815-822, 2012. Butler, L.M., H.C. Jeffery, R.L. Wheat RL, P.C. Rae, H.M. Long, G.B. Nash & D.J. Blackbourn. KSHV inhibits expression and function of endothelial cell MHC class II via suppressor of cytokine signalling 3. J.Virol. 86: 7158-7166, 2012.
Misstear, K., S.A. Chanas, S.A.R. Rezaee, R. Colman, A.S. Solovyova, L.L. Quinn, H.M. Long, J.M. Lord, J.A. Gracie, I.B. McInnes, A.D. Hislop and D.J. Blackbourn. Suppression of antigen-specific T cell responses by the KSHV vOX2 protein and its cellular orthologue, CD200. J.Virol. 86: 6246-6257, 2012.
Berhane, S., C. Aresté, J. Ablack, G. Ryan, D.J. Blackbourn, J.S. Mymryk, A.S. Turnell, J.C. Steele & R.J.A. Grand. Adenovirus E1A interacts directly with, and regulates the level of expression of, the immunoproteasome component MECL1. Virology, 421: 149-158, 2011.
Mutocheluh, M., L. Hindle, C. Aresté, S.A. Chanas, L.M. Butler, K. Lowry, K. Shah, D.J. Evans & D.J. Blackbourn. KSHV vIRF-2 inhibits type 1 interferon signalling by targeting ISGF-3. J. Gen. Virol., 92: 2394-8, 2011.
Jackson, B.R., J.R. Boyne, M. Noerenberg, A. Taylor, G.M. Hautbergue, M.J. Walsh, R. Wheat, D.J. Blackbourn, S.A. Wilson, A. Whitehouse. An interaction between KSHV ORF57 and UIF provides mRNA-adaptor redundancy in herpesvirus intronless mRNA export. PLoS Pathog. 2011 Jul;7(7):e1002138. Epub 2011 Jul 21.
Butler L.M., H.C. Jeffery, R.L. Wheat, P.C. Rae, K. Townsend, K.R. Alkharsah, T.F. Schulz, G.B. Nash and D.J. Blackbourn. KSHV inhibits neutrophil recruitment through an IL-6 dependent mechanism - a new paradigm for viral immune evasion. J. Virol. 85: 7321-7332, 2011.
Taylor, G.S. and D.J. Blackbourn. Immunomodulation by infectious agents in human cancers: Lessons from gammaherpesviruses EBV and KSHV. Cancer Letters 305: 263-278, 2011.
Durrington, H.J., P.D. Upton, S. Hoer, J. Boname, B. Dunmore, J. Yang, T.K. Crilley, L.M. Butler, D.J. Blackbourn, G.B. Nash, P.J. Lehner, N.W. Morrell. Identification of a lysosomal pathway regulating degradation of the bone morphogenetic protein receptor type-II. J. Biol. Chem. 285: 37641-49, 2010.
Aresté, C., M. Mutocheluh, M. and D.J. Blackbourn. Identification of Caspase-mediated Decay of Interferon Regulatory Factor-3, Exploited by a Kaposi Sarcoma-associated Herpesvirus Immunoregulatory Protein. J. Biol. Chem. 284: 23272-85, 2009.
Aresté, C. and Blackbourn, D.J. Modulation of the immune system by Kaposi's sarcoma-associated herpesvirus. Trends in Microbiology. 17:119-129, 2009.
Wang, L., M. Pietrek, M. Brinkmann, A. Hävemeier, I. Fischer, B. Hillenbrand, O. Dittrich-Breiholz, M. Kracht , S. Chanas, D.J. Blackbourn and T.F. Schulz. Identification and functional characterization of a spliced Rhesus Rhadinovirus gene with homology to the K15 gene of Kaposi's sarcoma-associated herpesvirus. J. Gen. Virol. 90:1190-1201, 2009.
Okroj, M., L. Mark, A. Stokowska, S.W. Wong, D.J. Blackbourn, O.B. Spiller, A. Blom. Characterization of the complement inhibitory function of Rhesus Rhadinovirus complement control protein (RCP). J. Biol. Chem. 284:505-514, 2009.
Mark, L., D.G. Proctor, D.J. Blackbourn, A.M. Blom, O.B. Spiller. Separation of decay-accelerating and cofactor functional activities of KSHV complement control protein (KCP) using monoclonal antibodies. Immunology. 123:228-38, 2008.
Colman, R. and D.J. Blackbourn. Cofactors in KS Development. AIDS. 22:1629-32, 2008.
Objective: Vitamin D deficiency (serum 25-hydroxyvitamin D˂25nmol/L) is extremely common in western-dwelling South Asians but evidence regarding vitamin D supplement usage in this group is very limited. This work identifies demographic, dietary and lifestyle predictors associated with vitamin D supplement use.
Design: Cross-sectional analysis of baseline vitamin D supplement use data.
Setting: UK Biobank cohort.
Subjects: In total, n 8024 South Asians (Bangladeshi, Indian, Pakistani), aged 40-69 years.
Results: Twenty-three % of men and 39% of women (P˂0.001) [22% of Bangladeshis, 32% of Indians, 25% of Pakistanis (P˂0.001)] took a vitamin D containing supplement. Median vitamin D intakes from diet were low at 1.0-3.0 micrograms per day, being highest in Bangladeshis and lowest in Indians (P˂0.001). Logistic regression modelling showed that females had a higher odds of vitamin D supplement use than males (odds ratio (OR) = 2.02; 95% confidence interval (CI) 1.79 to 2.28). A lower supplement usage was seen in younger persons (40-60 years) (OR=0.75; 95% CI 0.65 to 0.86 reference= ˃60 years), and those living outside of Greater London (OR=0.53 to 0.77), with borderline trends for a lower body mass index, higher oily fish intake and higher household income associated with increased odds of vitamin D supplement use.
Conclusions: Vitamin D supplements were not used by most South Asians and intakes from diet alone are likely to be insufficient to maintain adequate vitamin D status. Public health strategies are now urgently required to promote the use of vitamin D supplements in these specific UK South Asian sub-groups.
Background Aflatoxin B1 (AFB1) contamination of food is very high in most sub-Saharan African countries. AFB1 is known to cause hepatocellular carcinoma (HCC) by inducing mutation in the tumour suppressor gene TP53. The number of new HCC cases is high in West Africa with an accompanying high mortality. The type I interferon (IFN) pathway of the innate immune system limits viral infections and exerts its anti-cancer property by up-regulating tumour suppressor activities and pro-apoptotic pathways. Indeed, IFN-α is reported to show significant protective effects against hepatic fibrogenesis and carcinogenesis. However, the mechanism behind AFB1 deregulation of the type I interferon (IFN) signalling pathway, with consequent HCC is largely unknown. This current study seeks to test the hypothesis that AFB1 inhibits the type I IFN response by directly interfering with key signalling proteins and thus increase the risk of HCC in humans.
Methods We evaluated the effects of AFB1 on the type I IFN signalling pathway using IFN stimulated response element (ISRE)-based luciferase reporter gene assay. In addition, the effects of AFB1 on the transcript levels of JAK1, STAT1 and OAS3 were assessed by real-time quantitative polymerase chain reaction (RT-qPCR) and confirmed by immunoblot assay.
Results Our results indicated that AFB1 inhibited the type I IFN signalling pathway in human hepatoma cell line HepG2 cells by suppressing the transcript levels of JAK1, STAT1 and OAS3. AFB1 also decreased the accumulation of STAT1 protein.
Conclusion The inhibition of the type I IFN anti-cancer response pathway by AFB1 suggest a novel mechanism by which AFB1 may induce hepatocellular carcinoma in humans.