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Professor Simon Waddell

Professor Simon Waddell (BSc, PhD, FHEA)

Professor of Microbial Pathogenesis
E: S.Waddell@bsms.ac.uk
Location: BSMS Medical Research Building, University of Sussex, Falmer, Brighton, BN1 9PX

Areas of expertise: Molecular bacteriology; transcriptional profiling; host-pathogen interactions; AMR

Research areas: Tuberculosis drug discovery; mycobacterial pathogenesis; TB biomarkers; Non-tuberculous mycobacteria (NTM)

Other Roles: Lab lead and Deputy Head of Department for Global Health and Infection; Infection theme lead; Chair of the Laboratory Science Management Group; Module lead for BSMS 404 ‘4th Year Independent Research Project’ (2013-2024); Secretary to the Acid Fast Club; Chair of the NTM Network UK Basic Science Group

Read about the TB/NTM research team at BSMS >

Biography

Prof Simon Waddell trained in molecular microbiology at the University of Birmingham before completing a PhD in mycobacterial pathogenicity at St Georges, University of London. He then spent a stint as a postdoctoral scientist at Stanford University, US, profiling host responses to infection. He joined BSMS in 2010. His work focuses on understanding the interactions between host and pathogen, and investigating the action of anti-mycobacterial compounds through drug therapy. He has published in high impact journals such as Science, PLoS Medicine, BMC Medicine, Cell Host & Microbe, Nature Communications and Lancet Microbe, with funding from sources including BBSRC, MRC, NC3Rs, Royal Society and Wellcome Trust.

His ORCID ID is orcid.org/0000-0002-3684-9116;
ResearchGate ID is https://www.researchgate.net/profile/Simon_Waddell.
Full list of publications available at Sussex Research Online (SRO)

Research

The Waddell lab uses genome-wide technologies to understand mycobacterial (TB and NTM) drug action during human disease, to define bacterial populations that survive early drug therapy, and to identify the mode of action of novel anti-mycobacterial compounds. Our research also explores the interactions between host and pathogen throughout the disease process using transcriptional signatures derived from immune cells and M.tuberculosis to better explain pathogenicity and to reveal novel approaches to treatment.

Over 10 million people caught tuberculosis (TB) in 2023 and 1.25 million people died of the disease. Globally up to 2 billion people may be infected with the causative agent, Mycobacterium tuberculosis. TB remains one of the top 10 causes of death worldwide.

The standard drug therapy for TB uses combinations of 4 drugs over 6 months. The recommended treatment for multidrug-resistant TB lasts 18–24 months or more, with increasingly toxic combinations of second-line drugs. New drug regimens are needed to maintain and improve therapy for tuberculosis, shortening treatment duration and targeting drug-resistant bacteria.

The Waddell group is currently working on projects such as TBGEN (An integrated approach to unravelling susceptibility to tuberculosis in Africa) with African colleagues (https://tbgen.ahri.gov.et/); FLIGHT (Framework for Leveraging Innovation in Global Health Technologies); and with the UK Health Security Agency (UKHSA).

Teaching

Simon teaches in Years 1-4 of the BM-BS medical degree at BSMS and contributes to the MSc in Global Health. He lectures genome biology and infectious diseases and runs student-selected components. He was module leader for BSMS 404 ‘4th Year Independent Research Project’ (2013-2024). He is also an academic tutor. He supervises BSc/MSc project students, medical students and PhD research projects.

Selected publications

Gap-Gaupool B, Glenn SM, Milburn E, Turapov O, Crosatti M, Hincks J, Stewart B, Bacon J, Kendall SL, Voskuil MI, Riabova O, Monakhova N, Green J, Waddell SJ, Makarov VA, Mukamolova GV (2024). Nitric oxide induces the distinct invisibility phenotype of Mycobacterium tuberculosis. Commun Biol; 7(1):1206. PMCID: PMC11439070. DOI: 10.1038/s42003-024-06912-0. https://www.nature.com/articles/s42003-024-06912-0

Roberts AH, Moon CW, Faulkner V, Kendall SL, Waddell SJ, Bacon J (2024). EfpA is required for regrowth ofMycobacterium tuberculosis following isoniazid exposure. Antimicrob Agents Chemother; e0026124. PMCID: PMC11304720. DOI: 10.1128/aac.00261-24. https://journals.asm.org/doi/10.1128/aac.00261-24

Yang JJ, Goff A, Wild DJ, Ding Y, Annis A, Kerber R, Foote B, Passi A, Duerksen JL, London S, Puhl AC, Lane TR, Braunstein M, Waddell SJ, Ekins S (2024). Computational drug repositioning identifies niclosamide and tribromsalan as inhibitors of Mycobacterium tuberculosis and Mycobacterium abscessus. Tuberculosis (Edinb); 146:102500. PMCID: PMC10978224. DOI: 10.1016/j.tube.2024.102500. https://www.sciencedirect.com/science/article/pii/S147297922400026X?via%3Dihub

Cui Y, Lanne A, Peng X, Browne E, Bhatt A, Coltman NJ, Craven P, Cox LR, Cundy NJ, Dale K, Feula A, Frampton J, Fung M, Morton M, Goff A, Salih M, Lang X, Li X, Moon C, Pascoe J, Portman V, Press C, Schulz-Utermoehl T, Lee S, Tortorella MD, Tu Z, Underwood ZE, Wang C, Yoshizawa A, Zhang T, Waddell SJ, Bacon J, Alderwick L, Fossey JS, Neagoie C (2024). Azetidines Kill Multidrug-Resistant Mycobacterium tuberculosis without Detectable Resistance by Blocking Mycolate Assembly. J Med Chem; doi: 10.1021/acs.jmedchem.3c01643. PMCID: PMC10895678.https://pubs.acs.org/doi/10.1021/acs.jmedchem.3c01643

Hailu E, Cantillon D, Madrazo C, Rose G, Wheeler PR, Golby P, Adnew B, Gagneux S, Aseffa A, Gordon SV, Comas I, Young DB, Waddell SJ, Larrouy-Maumus G, Berg S (2023). Lack of methoxy-mycolates characterizes the geographically restricted lineage 7 of Mycobacterium tuberculosis complex. Microb Genom; 9(5):mgen001011. PMCID: PMC10272862. DOI: 10.1099/mgen.0.001011.https://www.microbiologyresearch.org/content/journal/mgen/10.1099/mgen.0.001011

Cantillon D, Goff A, Taylor S, Salehi E, Fidler K, Stoneham S, Waddell SJ (2022). Search for new therapeutic options for the uncommon pathogen Mycobacterium chimaera: an open drug discovery approach. Lancet Microbe; 3(5):e382-e391. PMCID: PMC9042791. DOI: 10.1016/S2666-5247(21)00326-8.https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(21)00326-8/fulltext

Cantillon D, Wroblewska J, Cooper I, Newport MJ, Waddell SJ (2021). Three-dimensional low shear culture ofMycobacterium bovis BCG induces biofilm formation and antimicrobial drug tolerance. npj Biofilms Microbiomes; 7 (12). PMCID: PMC7851154. DOI: 10.1038/s41522-021-00186-8. https://www.nature.com/articles/s41522-021-00186-8

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