Professor Peter Ghazal

Professor Peter Ghazal

Sêr Cymru Chair in Systems Medicine, Systems Immunity Research Institute

School of Medicine

Prof Ghazal's research interests are aimed towards understanding how host-gene networks control infection, especially with those host-pathways associated with sepsis and the immune-metabolic axis.

His recent studies have pioneered the field of host genomics of early-life infection, mapping and deciphering gene metabolic signatures of systemic host response to infection in pre-term infants and neonates and understanding the molecular wiring and mechanisms for coupling lipid metabolism to immune (interferon) response.

These studies are specifically aimed at the development of new diagnostic and therapeutic strategies, including predictive modelling of host-defence against infection in sepsis, and the development of new computational and functional genomic methods for gaining a deeper understanding of complex dynamical biological systems of viral (cytomegaloviral) and microbial diseases.

Selected Publications

  1. Dantoft W, Martínez-Vicente P, Jafali J, Pérez-Martínez L, Martin K, Kotzamanis K, Craigon M, Auer M, Young NT, Walsh P, Marchant A, Angulo A, Forster T and P. Ghazal. Genomic programming of human neonatal dendritic cells in congenital systemic and in vitro cytomegalovirus infection reveal plastic and robust immune pathway biology responses. Front Immunol 8:1146. doi: 10.3389/fimmu.2017.01146. (2017)
  2. Duffin R, O’Connor RA, Crittenden S, Forster T, Yu C, Zheng X, Smyth D, Robb CT, Rossi F, Skouras C, Tang S, Richards J, Pellicoro A, Weller RB, Breyer RM, Mole DJ, Iredale JP, Anderton SM, Narumiya S, Maizels RM, Ghazal P, Howie SE, Rossi AG and C. Yao Prostaglandin E2 constrains systemic inflammation through an innate lymphoid cell-IL-22 axis. Science 351: 1333 – 1338 (2016).
  3. Robertson KA, Hsieh WY, Forster T, Blanc M, Hongjin L, Crick PJ, Yutuc, E, Watterson S, Martin K, Griffiths SJ, Wang Y, Angulo A and P. Ghazal. An interferon- induced microRNA provides broad cell-intrinsic anti-viral immunity through multi-hit host-directed targeting of the sterol pathway. PLoS Biol. 14(3):e1002364. doi: 10.1371/journal.pbio.1002364. (2016)
  4. Smith C, Dickinson P, Forster T, Craigon M, Ross A, Khondoker M, France R, Ivens A, Lynn D, Orme J, Jackson A, Lacaze P, Flanagan, Stenson Ghazal P, Identification of a human neonatal immune-metabolic network associated with bacterial infection. Nature comm. 14;5:4649
  5. Hambleton S, Goodbourn S, Young DF, Dickinson P, Mohamad SM, Valappil M, McGovern N, Cant Hackett SJ, AJ, Ghazal P, Morgan NV, RE Randall. STAT2 deficiency and susceptibility to viral illness in humans. Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):3053-8.
  6. Blanc M, Hsieh WY, Robertson KA, Kropp KA, Forster T, Shui G, Lacaze, Watterson, Griffiths SJ, Spann NJ, Talbot S, Covey DF, Wenk MR, Craigon M, Ruzsics Z, Angulo A, Griffiths WJ, Glass CK, Wang Y P Ghazal. The transcription factor STAT-1 couples macrophage synthesis of 25-hydroxycholesterol to the interferon antiviral response. Immunity. 2013 38(1): 106-18.
  7. Blanc M, WY Hsieh, KA Robertson, S Watterson, G Shui, P Lacaze, M Khondoker, P Dickinson, G Sing, S Rodríguez-Martín, P Phelan, T Forster, B Strobl, M Müller, R Riemersma, T Osborne, MR Wenk, A Angulo and P Ghazal. Host defense against viral infection involves interferon mediated down-regulation of sterol biosynthesis. PLoS Biol. 9 2011.
  8. Santhakumar D, T Forster, NN Laqtom, R Fragkoudis, P Dickinson, C Abreu-Goodger, SA Manakov, NR  Choudhury, A Vermeulen, SJ Griffiths, AJ Enright, B Dutia, A Kohl, P Ghazal and AH Buck. Combined agonist-antagonist genome-wide functional screening identfies broadly active antiviral microRNAs. Proc. Natl. Acad. Sci. USA 107: 13830 – 18835. 2010
  9. Novère NL, M Hucka, H Mi, S Moodie, F Schreiber, A Sorokin, E Demir, K. Wegner, MI Aladjem, SM Wimalaratne, FT Bergman, R Gauges, P Ghazal, et al. The systems biology graphical notation. Nature Biotechnol. 8: 735 -741. 2009.
  10. Birmingham A, LM Selfors, T Forster, D Wrobel, CJ Kennedy, E Shanks, J Santoyo-Lopez, DJ Dunican, A Long, Q Smith, RL Beijersbergen, P Ghazal, CE Shamu. Statistical methods for analysis of high-throughput RNA interference screens. Nature Methods 6: 569 – 575. 2009.
  11. Taylor CF, D. Field, S-A Sansone, R Apweiler, M Ashburner, CA Ball, P-A. Binz, A Brazma, R Brinkman, EW Deutsch, O Fiehn, J Fostel, P Ghazal, et al. Promoting coherent minimum reporting requirements for biological and biomedical investigations: The MIBBI project. Nature Biotechnol. 26: 889 - 896. 2008.
  12. Wilson WH, DC Schroeder, MJ Allen, MTG Holden, J Parkhill, BG Barrell, C Churcher, N Hamlin, K Mungall, H Norbertczak, MA Quail, C Price, E Rabbinowitsch, D Walker, M Craigon, D Roy and P Ghazal. Complete genome sequence and lytic phase transcription profile of a Coccolithovirus. Science 309: 1090 – 1092. 2005.
  13. Benedict CA, TA Banks, L Senderowicz, M Ko, WJ Britt, A Angulo, P Ghazal, CF Ware. Lymphotoxins and cytomegalovirus cooperatively induce interferon-β establishing host-virus détente. Immunity. 15: 617-626, 2001
  14. Monier K., JC González-Armas, S Etteldorf, P Ghazal and KF Sullivan. Annexation of the interchromosomal space during infection. Nature Cell Biol.  2: 661-665, 2000.
  15. Wang H, MN Griffiths, DR Burton, P Ghazal. Rapid antibody responses by low-dose, single-step, dendritic cell-targeted immunization. Proc.Natl. Acad. Sci. USA 97: 847-852, 2000.
  16. Preckel T, WP Fung-Leung, Z Cai, A Vitiello, L Salter-Cid, O Winqvist, TG Wolfe, M von Herrath, A Angulo, P Ghazal, et al. Impaired immunoproteosome assembly and immune responses in PA28-/- mice. Science 286: 2162-2165, 1999
  17. Chambers, J., A. Angulo, D. Amaratunga, H.C Gao, Y. Jiang, J.S. Wan, A. Bittner, K. Frueh, M.R. Jackson, P.A. Peterson, M.G. Erlander, and P. Ghazal. DNA microarrays of the complex human cytomegalovirus genome:  Profiling kinetic class with drug sensitivity of viral gene expression. J. Virol. 73: 5757-5766, 1999.
  18. Kanakaraji, P., K. Ngo, Y. Wu, A. Angulo, P. Ghazal, C.A. Harris, J.J. Siekierka, P.A. Peterson, and W.-P. Fung-Leung. Defective interleukin (IL)-18-mediated natural killer and T helper cell type 1 responses in IL-1 receptor-associated kinase (IRAK)-deficient mice. J. Exp. Med.  189: 1129-1138, 1999.
  19. Ahn, K., A. Angulo, P. Ghazal, P.A. Peterson, Y. Yang, and K. Früh. Human cytomegalovirus inhibits antigen presentation by a sequential multi-step process. Proc. Natl. Acad. Sci. USA.  93: 10990-10995, 1996.
  20. Lee, G., J. Wu, P. Luu, P. Ghazal, and O. Flores. Inhibition of the association of RNA polymerase II with the pre-initiation complex by a viral transcriptional repressor. Proc. Natl. Acad. Sci. USA.  93: 2570-2575, 1996
  21. Ghazal, P., C. DeMattei, E. Giulietti, S.A. Kliewer, K. Umesono, and R.M. Evans. Retinoic acid receptors initiate induction of the cytomegalovirus enhancer in embryonal cells. Proc. Natl. Acad. Sci. USA.  89: 7630-7634, 1992.
  22. Ghazal, P., H. Lubon, B. Fleckenstein, and L. Hennighausen. Binding of transcription factors and creation of a large nucleoprotein complex on the human cytomegalovirus enhancer. Proc. Natl. Acad. Sci. USA 84:3658-3662, 1987
  23. Ghazal, P., A.J. Clark, and J.O. Bishop. Evolutionary amplification of a pseudogene. Proc. Natl. Acad. Sci. USA 82:4182-4185, 1985.

Professor Peter Ghazal FMedSci holds the Sêr Cymru II Chair of Systems Medicine at Cardiff Medical School, Systems Immunity Research Institute and is Honorary Professor of Molecular Genetics and Biomedicine at the University of Edinburgh Medical School. He was founding Director of the Scottish Centre for Genomic Technology and Informatics and former Head of the Division of Pathway Medicine, Associate Director of Centre for Synthetic and Systems Biology at Edinburgh. Prior to joining Edinburgh Medical School, he was Associate Professor at the Scripps Research Institute in La Jolla, California and a Scholar of the American Leukemia Society.

His research interests are in the field of host genomics of early-life infection, mapping immune (interferon) networks of systemic host response to infection and understanding the link between lipid metabolism and host protection pathways.

These studies are specifically aimed at the development of new diagnostic and therapeutic strategies, including predictive modelling of host-defence against infection. He has been actively involved in a range of collaborative clinical investigations conducted in the UK and in Africa with the MRC Gambia unit using a systems biology approach to better understand neonatal sepsis, and deciphering the molecular systems immunology of childhood pneumonia and vaccine responses.

His career spans 15 years in the USA (as a Fellow at NIH and subsequently as Faculty member at The Scripps Research Institute, Department of Immunology) and the last 17 years in the UK, he has published over 200 papers and 9 patents and founder of three start-up companies.

Professor Ghazal  has served on a number of national and international advisory boards, think tanks, and review committees within both academia, industry, charitable and government bodies in the UK, EU, USA and Canada, including most recently Chair of the Virus Scientific Advisory Board for the Wellcome Trust Sanger Institute, and a member of the Scientific Advisory Board for the NIH NIAID Human Immunology Project Consortium in the USA.  He was elected Fellow of the Academy of Medical Sciences in 2015.