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Dr Timothy Wells

Senior Research Fellow in HMR

Frazer Institute
Faculty of Medicine
timothy.wells@uq.edu.au

Overview

Dr Timothy Wells joined the Frazer Institute in 2016 as a Senior Research Fellow. His research aims to find novel methods of treating multi-drug resistant bacteria, by examing the interactions between the host immune system and Gram negative bacteria. His research largely focuses on Pseudomonas aeruginosa acute and chronic infections, espeically in people living with cystic fibrosis. Dr Wells is passionate about making his research as clinically relevant as possible, with his work previously having led to novel treatment of critically ill patients. His research uses a mixture of molecular microbiology, immunology and genomic approaches.

Research Interests

  • Pseudomonas aeruginosa
    The T-Wells lab is interested in all infections by Pseudomonas aeruginosa whether that be chronic lung infection, wound and joint infections, acute pneumonia, UTIs and bacteremia.
  • Bacterial chronic lung infections
    The T-Wells lab is interested in bacterial infections in people with cystic fibrosis, bronchiectasis, COPD and post-lung transplant

Research Impacts

Dr Wells’s original work in the field of host- pathogen interactions during chronic lung infection has led to several key insights and direct translation to the clinic.

Antibody dependent enhancement of bacterial infection: Antibodies usually protect against bacterial infection, however Dr Wells' work has identified ‘cloaking antibodies’ in patients who have Pseudomonas aeruginosa infections. Cloaking antibodies paradoxically prevent immune killing of patient's bacterial strains. Importantly, high titres of cloaking antibodies has been associated with worse lung function and patient outcomes in people with cystic fibrosis, bronchiectasis and post-lung transplant. These antibodies are also prevelant in actue Pseduomonas infections such as bacteremia.

Novel treatment of multi-drug resistant Pseudomonas aeruginosa lung infection: As cloaking antibodies (cAbs) protect bacteria from immune killing, we hypothesised that cAb removal would restore normal immune killing. Three patients with chronic P. aeruginosa infections and cAb, who had exhausted all standard treatment options have now been treated via plasmapheresis. This treatment removes all antibody, including cAbs from the patients. After treatment, P. aeruginosa was undetectable in all patients, inflammatory markers were normal and lung function increased. As these patients had strains displaying resistance to many antibiotics used clinically, this is a novel treatment method for multi-drug resistant infections.

Qualifications

  • Doctor of Philosophy, The University of Queensland
  • Bachelor (Honours) of Biotechnology, The University of Queensland

Publications

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Grants

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Supervision

View all Supervision

Available Projects

  • Synergistic drugs to counteract cloaking antibodies

    Some patients infected with P. aeruginosa produce antibodies that, instead of fighting infection, actively protect P. aeruginosa from killing by the immune system. These ‘cloaking antibodies’ (cAb) target a lipopolysaccharide on the bacterial surface, known as O-antigen and form a physical barrier that stops the membrane attack complex (MAC) from reaching the bacterial outer membrane. Importantly, patients with cAb had greater disease severity and worse outcomes than patients with no cAb. Previous treatment for cAbs has focused on removal of the antibody, however a second attractive target is the infecting bacteria itself. We have recently investigated the bacterial requirements for the cloaking phenotype by creating strains with variable amounts and lengths of O-antigen expression. Serum bactericidal assays revealed that the serum-inhibition phenotype requires long and dense O-antigen We hypothesise that existing bacterial outer membrane modifying drugs can overcome the effect of cAbs, without cAb removal. This project will investigate potential synergistic drugs that could counteract cAbs, leading to bacterial killing.

View all Available Projects

Publications

Featured Publications

Book Chapter

  • Type 1 and 5 secretion systems and associated toxins

    Wells, Timothy J. and Henderson, Ian R. (2013). Type 1 and 5 secretion systems and associated toxins. Escherichia coli: pathotypes and principles of pathogenesis. (pp. 499-532) edited by Michael S. Donnenberg. Cambridge, MA, United States: Academic Press. doi: 10.1016/B978-0-12-397048-0.00016-4

Journal Article

Conference Publication

  • Goblet cell specific anti-apoptotic role of interleukin-24 in spondyloarthritis-associated ileitis

    Cameron, A., Giri, R., Begun, J., Wells, T., Bergot, A. S. and Thomas, R. (2023). Goblet cell specific anti-apoptotic role of interleukin-24 in spondyloarthritis-associated ileitis. EULAR 2023 European Congress of Rheumatology, Milan, Italy, 31 May-3 June 2023. London, United Kingdom: BMJ Group. doi: 10.1136/annrheumdis-2023-eular.1346

  • TIGIT limits anti-bacterial immunity and is a potential target for immunotherapy

    Souza-Fonseca-Guimaraes, Fernando, Rossi, Gustavo Rodrigues, Wells, Timothy and McCulloch, Timothy Ryan (2023). TIGIT limits anti-bacterial immunity and is a potential target for immunotherapy. IMMUNOLOGY2023™ Meeting, Washington, DC, United States, 11 - 15 May 2023. Rockville, MD, United States: The American Association of Immunologists. doi: 10.4049/jimmunol.210.supp.64.14

  • A Novel Pseudomonas aeruginosa Virulence Factor Predicts CLAD and Death after Lung Transplantation

    Divithotawela, C., Pham, A., Ledger, E. L., Hopkins, P., Tan, M., Yerkovich, S., Wells, T. J. and Chambers, D. C. (2020). A Novel Pseudomonas aeruginosa Virulence Factor Predicts CLAD and Death after Lung Transplantation. International Society for Heart and Lung Transplantation 40th Annual Meeting and Scientific Sessions, Online, 22 - 25 April 2020. Philadelphia, PA United States: Elsevier. doi: 10.1016/j.healun.2020.01.1265

  • A Novel Pseudomonas aeruginosa Virulence Factor Predicts CLAD and Death after Lung Transplantation

    Divithotawela, C., Pham, A., Ledger, E. L., Hopkins, P., Tan, M., Yerkovich, S., Wells, T. J. and Chambers, D. C. (2020). A Novel Pseudomonas aeruginosa Virulence Factor Predicts CLAD and Death after Lung Transplantation. 40th Annual Meeting and Scientific Sessions of the International Society for Heart and Lung Transplantation (ISHLT), Montreal, Canada, 22-25 April 2020. New York, NY United States: Elsevier.

  • Chlamydia-Infected Macrophages: "Trojan Horses" for Dissemination of IL-23 and TNF-Mediated Inflammation in SKG Mouse Reactive Arthritis

    Baillet, Athan, Bhuyan, Zaied Ahmed, Douillard, Claire, Bozon, Aurelie, Armitage, Charles, Romand, Xavier, Minh Vu Chuong Nguyen,, Favier, Bertrand, Wells, Timothy, Beagley, Kenneth and Thomas, Ranjeny (2017). Chlamydia-Infected Macrophages: "Trojan Horses" for Dissemination of IL-23 and TNF-Mediated Inflammation in SKG Mouse Reactive Arthritis. 2017 ACR/ARHP Pediatric Rheumatology Symposium, San Diego, CA, United States, 3-8 November 2017. Hoboken, NJ, United States: John Wiley & Sons.

  • Functional genomics of the regulation of nodule number in legumes

    Gresshoff, PM, Gualtieri, G, Laniya, T, Indrasumunar, A, Miyahara, A, Nontachaiyapoom, S, Wells, T, Biswas, B, Chan, PK, Scott, P, Kinkema, M, Djordjevic, M, Hoffmann, D, Pregelj, L, Buzas, DM, Li, DX, Men, A, Jiang, Q, Hwang, CH and Carroll, BJ (2005). Functional genomics of the regulation of nodule number in legumes. 14th International Nitrogen Fixation Congress, Beijing, China, 27 October - 1 November 2004. The Netherlands: Springer. doi: 10.1007/1-4020-3570-5

  • Functional genomic analysis of nodule development in soybean and Lotus Japonicus

    Gresshoff, P. M., Carroll, B. J., Gualtieri Gonzalez, G. S., Vickers, C., Kuen, P., Huang, C., Scott, P. T., Kinkema, M. D., Men, A., Stiller, J., Jiang, Q., Laniya, T.S., Buzas, D. M., Miyahara, A., Indrasumunar, A., Nontachaiyapoom, S., Hoffmann, D., Biswas, B., Wells, T. J., So, H., Pregelj, L. and Dong, X. (2004). Functional genomic analysis of nodule development in soybean and Lotus Japonicus. Com Bio 2004, Intercontinental Burswood Resort, Perth, Australia, 26-30 September, 2004.

Other Outputs

PhD and MPhil Supervision

Current Supervision

  • The role of Two Partner Secretion proteins in the virulence of Pseudomonas aeruginosa

    Doctor Philosophy — Principal Advisor

    Other advisors:

  • Antibody mediated exacerbation of Pseudomonas aeruginosa infected chronic wounds

    Master Philosophy — Principal Advisor

    Other advisors:

  • The role of cloaking antibodies in the pathophysiology, diagnosis, and treatment of inflammatory diseases

    Doctor Philosophy — Principal Advisor

    Other advisors:

  • Investigating the gram-negative bacterial and host factors that drive sepsis outcomes

    Doctor Philosophy — Principal Advisor

    Other advisors:

  • Investigating B cell responses to Pseudomonas O-Antigen

    Doctor Philosophy — Principal Advisor

    Other advisors:

  • The impact of helpful and harmful immune responses on infection in the cystic fibrosis lung

    Doctor Philosophy — Principal Advisor

  • Deciphering the protective program of innate and adaptive cells in pathogen infection

    Doctor Philosophy — Associate Advisor

    Other advisors:

  • Characterisation of the anti-mycobacterial activity of wollamide cyclic hexapeptides against Mycobacterium tuberculosis

    Doctor Philosophy — Associate Advisor

    Other advisors:

  • The role of endoplasmic reticulum stress in spondyloarthropathy

    Doctor Philosophy — Associate Advisor

    Other advisors:

Possible Research Projects

Note for students: The possible research projects listed on this page may not be comprehensive or up to date. Always feel free to contact the staff for more information, and also with your own research ideas.

  • Synergistic drugs to counteract cloaking antibodies

    Some patients infected with P. aeruginosa produce antibodies that, instead of fighting infection, actively protect P. aeruginosa from killing by the immune system. These ‘cloaking antibodies’ (cAb) target a lipopolysaccharide on the bacterial surface, known as O-antigen and form a physical barrier that stops the membrane attack complex (MAC) from reaching the bacterial outer membrane. Importantly, patients with cAb had greater disease severity and worse outcomes than patients with no cAb. Previous treatment for cAbs has focused on removal of the antibody, however a second attractive target is the infecting bacteria itself. We have recently investigated the bacterial requirements for the cloaking phenotype by creating strains with variable amounts and lengths of O-antigen expression. Serum bactericidal assays revealed that the serum-inhibition phenotype requires long and dense O-antigen We hypothesise that existing bacterial outer membrane modifying drugs can overcome the effect of cAbs, without cAb removal. This project will investigate potential synergistic drugs that could counteract cAbs, leading to bacterial killing.

This staff member is a UQ Expert for media in the following fields:

Pseudomonas aeruginosa, cystic fibrosis infections

They are happy to lend their expertise to your articles or broadcasts and share their research discoveries and insights with the community via media channels.

For additional assistance with story ideas, general advice and information or help with seeking further experts, please email the UQ Media Team or telephone (07) 3365 1120.

Links

ResearcherID: M-2025-2016

ORCID: 0000-0001-7766-5404

Scopus ID: 18635582900

Google Scholar ID:

Personal Profile: Link

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