Dr Strang joined SGUL in 2013 as a tenure-track non-clinical Lecturer in Infection and Immunity and became Lecturer in Virology in 2016.

Dr Strang was awarded an undergraduate degree from the University of Glasgow (1995-1999) and was awarded a PhD from University College London (1999-2003). He carried out post-doctoral research at the Medical Research Council Virology Unit (2003-2006) and Harvard Medical School (2006-2013).

Our laboratory investigates the replication and pathogenesis of human viral pathogens with a view to the development of antiviral drugs. We are interested in viruses that affect both our patient population at St George’s and global health. Of particular interest is human cytomegalovirus.

Human cytomegalovirus (HCMV) is a widespread opportunistic human pathogen that is a major cause of human morbidity and mortality. Over 60% of the population worldwide are infected. HCMV infection is associated with a range of disease in humans, including numerous neurological abnormalities in newborns and infants, such as hearing loss, vision loss and cerebral palsy. HCMV is also a factor in organ transplant rejection and the rate of progression of acquired immunodeficiency syndrome. Links between infection, hypertension, atherosclerosis and cancer have been reported.

There is no widely available HCMV vaccine and currently available anti-HCMV drugs have many shortcomings, including issues surrounding drug resistance. Novel anti-HCMV drugs are urgently required.

The major aims of our human cytomegalovirus research include:

Discovery and development of novel anti-viral compounds and proteins.

In collaboration with academic and industrial colleagues we have utilized high throughput screening to identify compounds that inhibit cellular proteins required for HCMV replication ^1-4. We also adapted our screening technology to perform genetic screens to identify host cell proteins that have the potential to be HCMV drug targets ⁵.

To extend this work in new and exciting directions we have also used machine learning to interrogate our screening results, identifying novel screening “hits” in our data ⁶. Plus, we have extended our interest in host cell factors required for HCMV replication to include nucleic acid, identifying compounds that interact with DNA which can inhibit anti-HCMV replication ⁷.

Our interests in these areas have been recently reviewed ⁸.

We are now assessing antiviral proteins such as interferons for use in antiviral therapy ^{9, 10} and have begun to assist in identification of proteins with antiviral properties that may be amenable to inhibition with small compounds ¹¹. Plus, we are now leveraging our understanding of antiviral activity against HCMV to understand antiviral activity against other viruses of medical importance. For example, antiviral compounds inhibiting replication of vaccinia virus and mpox virus ^{12, 13}.

HCMV pathogenesis – infection of the placenta/HCMV during pregnancy

In our view the most understudied area of viral pathogenesis, including HCMV pathogenesis, is how viral infection of the placenta causes disease in mother and infant. Using a bioinformatics approach we have sought to understand what DNA viruses can be found in the placenta ¹⁴. We find that DNA virus infection of placental tissue, including HCMV, appears to be rare. One possible interpretation of this data is that it is difficult for DNA viruses to establish infection in placental tissue. Our analysis of HCMV, herpes simplex virus and Zika virus replication in a well-known placental cell line suggests this may be true for some, but not all, viruses, including HCMV ¹⁵.

To complement these studies, we have also been involved in clinical studies surrounding the cCHIPS trial based at SGUL. Here, HCMV shedding was examined in parallel to patient engagement studies on knowledge of HCMV infection during pregnancy ^{16, 17}.

1. Ho, C.M. et al. Inhibition of IKKalpha by BAY61-3606 Reveals IKKalpha-Dependent Histone H3 Phosphorylation in Human Cytomegalovirus Infected Cells. PloS one 11, e0150339 (2016).
2. Beelontally, R. et al. Identification of compounds with anti-human cytomegalovirus activity that inhibit production of IE2 proteins. Antiviral research 138, 61-67 (2017).
3. Khan, A.S. et al. High-throughput screening of a GlaxoSmithKline protein kinase inhibitor set identifies an inhibitor of human cytomegalovirus replication that prevents CREB and histone H3 post-translational modification. J Gen Virol 98, 754-768 (2017).
4. Strang, B.L. RO0504985 is an inhibitor of CMGC kinase proteins and has anti-human cytomegalovirus activity. Antiviral research 144, 21-26 (2017).
5. Polachek, W.S. et al. High-Throughput Small Interfering RNA Screening Identifies Phosphatidylinositol 3-Kinase Class II Alpha as Important for Production of Human Cytomegalovirus Virions. J Virol 90, 8360-8371 (2016).
6. Strang, B.L. et al. Identification of lead anti-human cytomegalovirus compounds targeting MAP4K4 via machine learning analysis of kinase inhibitor screening data. PloS one 13, e0201321 (2018).
7. Falci Finardi, N. et al. Identification and characterization of bisbenzimide compounds that inhibit human cytomegalovirus replication. J Gen Virol 102 (2021).
8. Strang, B.L. Toward inhibition of human cytomegalovirus replication with compounds targeting cellular proteins. J Gen Virol 103 (2022).
9. Lista, M.J. et al. Strain-Dependent Restriction of Human Cytomegalovirus by Zinc Finger Antiviral Proteins. J Virol 97, e0184622 (2023).
10. Chowdhury, S. et al. Inhibition of human cytomegalovirus replication by interferon alpha can involve multiple anti-viral factors. J Gen Virol 104 (2023).
11. Nightingale, K. et al. Human cytomegalovirus protein RL1 degrades the antiviral factor SLFN11 via recruitment of the CRL4 E3 ubiquitin ligase complex. Proc Natl Acad Sci U S A 119 (2022).
12. Samolej, J. et al. Bisbenzimide compounds inhibit the replication of prototype and pandemic potential poxviruses. Microbiol Spectr 12, e0407223 (2024).
13. Samolej, J., White, I.J., Strang, B.L. & Mercer, J. Cardiac glycosides inhibit early and late vaccinia virus protein expression. J Gen Virol 105 (2024).
14. Witney, A.A., Aller, S. & Strang, B.L. Metagenomic profiling of placental tissue suggests DNA virus infection of the placenta is rare. J Gen Virol 102 (2021).
15. Hyde, K. et al. Limited replication of human cytomegalovirus in a trophoblast cell line. J Gen Virol 102 (2021).
16. Sapuan, S., Heath, P.T., Strang, B.L., Khalil, A. & Jones, C.E. Learning from the experiences of pregnant women participating in a research study investigating human cytomegalovirus shedding: A qualitative study. PloS one 18, e0292134 (2023).
17. Sapuan, S., Theodosiou, A.A., Strang, B.L., Heath, P.T. & Jones, C.E. A systematic review and meta-analysis of the prevalence of human cytomegalovirus shedding in seropositive pregnant women. Reviews in medical virology 32, e2399 (2022).

19 Dec 2024

ORCID iD 0000-0001-9407-1974

Link to access published articles from PubMed:

https://pubmed.ncbi.nlm.nih.gov/?term=strang_bl&sort=pubdate&size=200

We are very grateful to those who have supported our work – thank you!

Current or previous work in the laboratory is/has been supported by governmental (MRC, NIH), private (Wellcome Trust, Pandemic Institute) or biotechnology (Merck, Sharpe & Dohme, LifeArc, Boehringer Ingelheim GmbH) organizations, as well as personal fellowships, SGUL innovation awards and PhD Studentships (MRC CASE, MRC LID, Kingdom of Saudi Arabia).

Our sincerest thanks to those who have, and continue to, support work in our laboratory!

These include:

Dr Hassan Al-Ali (University of Miami)

Professor Donald Coen (Harvard Medical School)

Professor Andrew Davison (MRC Centre for Virus Research)

Professor Nathanael Grey (Harvard Medical School)

Professor Paul Heath (SGUL)

Dr Beth Holder (Imperial)

Dr Chrissie Jones (University of Southampton)

Professor Alain Kohl (University of Liverpool)

Professor Jason Mercer (University of Birmingham)

Dr Andy Merritt (LifeArc)

Professor Arvind Patel (MRC Centre for Virus Research)

Professor Stuart Neil (King’s College London)

Dr Matthew Reeves (UCL)

Dr Vattipally Sreenu (MRC Centre for Virus Research)

Professor Richard Stanton (Cardiff University)

Dr Chad Swanson (King’s College London)

Dr Adam Witney (SGUL)

Professor Michael Weekes (University of Cambridge)

Dr Bill Zuercher (University of North Carolina)

SGUL Summer School lecturer (2018-present)

Lecturer to SGUL BSc/iBSc, MPharm, MSci, MRes students (2014-present)

Administrator for SGUL BSc/iBSc Infection & Immunity research projects (2014-present)

Personal tutor to SGUL BSc/MBBS undergraduates (2014-present)

SGUL PhD, MRes, MSci, BSc/iBSc student laboratory supervisor (2013-present)