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Dr Timothy Wells
Dr

Timothy Wells

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Overview

Background

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.

Availability

Dr Timothy Wells is:
Available for supervision
Media expert

Qualifications

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

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.

Works

Search Professor Timothy Wells’s works on UQ eSpace

53 works between 2004 and 2024

1 - 20 of 53 works

Featured

2017

Journal Article

The Use of Plasmapheresis in Patients with Bronchiectasis with Pseudomonas aeruginosa Infection and Inhibitory Antibodies

Wells, Timothy J., Davison, John, Sheehan, Emma, Kanagasundaram, Suren, Spickett, Gavin, MacLennan, Calman A., Stockley, Robert A., Cunningham, Adam F., Henderson, Ian R. and De Soyza, Anthony (2017). The Use of Plasmapheresis in Patients with Bronchiectasis with Pseudomonas aeruginosa Infection and Inhibitory Antibodies. American Journal of Respiratory and Critical Care Medicine, 195 (7), 955-958. doi: 10.1164/rccm.201603-0599LE

The Use of Plasmapheresis in Patients with Bronchiectasis with Pseudomonas aeruginosa Infection and Inhibitory Antibodies

2024

Journal Article

Type 5 secretion system antigens as vaccines against Gram-negative bacterial infections

Da Costa, Rochelle M., Rooke, Jessica L., Wells, Timothy J., Cunningham, Adam F. and Henderson, Ian R. (2024). Type 5 secretion system antigens as vaccines against Gram-negative bacterial infections. npj Vaccines, 9 (1) 159. doi: 10.1038/s41541-024-00953-6

Type 5 secretion system antigens as vaccines against Gram-negative bacterial infections

2024

Journal Article

Cloaking antibodies are prevalent in Burkholderia cepacia complex infection and their removal restores serum killing

Pham, Amy, Tan, Kellynn K. Y., Ledger, Emma L., Smith, Daniel J., Reid, David W., Burr, Lucy, Chambers, Daniel C. and Wells, Timothy J. (2024). Cloaking antibodies are prevalent in Burkholderia cepacia complex infection and their removal restores serum killing. Frontiers in Cellular and Infection Microbiology, 14 1426773. doi: 10.3389/fcimb.2024.1426773

Cloaking antibodies are prevalent in Burkholderia cepacia complex infection and their removal restores serum killing

2024

Journal Article

Mechanisms of antibody-dependent enhancement of infectious disease

Wells, Timothy J., Esposito, Tyron, Henderson, Ian R. and Labzin, Larisa I. (2024). Mechanisms of antibody-dependent enhancement of infectious disease. Nature Reviews Immunology. doi: 10.1038/s41577-024-01067-9

Mechanisms of antibody-dependent enhancement of infectious disease

2024

Journal Article

The immune checkpoint TIGIT is upregulated on T cells during bacterial infection and is a potential target for immunotherapy

McCulloch, Timothy R, Rossi, Gustavo R, Miranda‐Hernandez, Socorro, Valencia‐Hernandez, Ana Maria, Alim, Louisa, Belle, Clemence J, Krause, Andrew, Zacchi, Lucia F, Lam, Pui Yeng, Nakamura, Kyohei, Kupz, Andreas, Wells, Timothy J and Souza‐Fonseca‐Guimaraes, Fernando (2024). The immune checkpoint TIGIT is upregulated on T cells during bacterial infection and is a potential target for immunotherapy. Immunology & Cell Biology. doi: 10.1111/imcb.12794

The immune checkpoint TIGIT is upregulated on T cells during bacterial infection and is a potential target for immunotherapy

2024

Journal Article

Impact of CFTR Modulation on <i>Pseudomonas aeruginosa</i> Infection in People With Cystic Fibrosis

Ledger, Emma L, Smith, Daniel J, Teh, Jing Jie, Wood, Michelle E, Whibley, Page E, Morrison, Mark, Goldberg, Joanna B, Reid, David W and Wells, Timothy J (2024). Impact of CFTR Modulation on Pseudomonas aeruginosa Infection in People With Cystic Fibrosis. The Journal of Infectious Diseases. doi: 10.1093/infdis/jiae051

Impact of CFTR Modulation on <i>Pseudomonas aeruginosa</i> Infection in People With Cystic Fibrosis

2024

Journal Article

Antibody-mediated serum resistance protects Pseudomonas aeruginosa during bloodstream infections

Hickson, Sarah M., Hoehensteiger, Johannes K., Mayer-Coverdale, Johanna, Torres, Von Vergel L., Feng, Wenkang, Monteith, Joshua N., Henderson, Ian R., McCarthy, Kate L. and Wells, Timothy J. (2024). Antibody-mediated serum resistance protects Pseudomonas aeruginosa during bloodstream infections. The Journal of Infectious Diseases, 230 (2), e221-e229. doi: 10.1093/infdis/jiad457

Antibody-mediated serum resistance protects Pseudomonas aeruginosa during bloodstream infections

2023

Journal Article

Genomic analyses of Burkholderia respiratory isolates indicates two evolutionarily distinct B. anthina clades

Pham, Amy, Volmer, James G., Chambers, Daniel C., Smith, Daniel J., Reid, David W., Burr, Lucy and Wells, Timothy J. (2023). Genomic analyses of Burkholderia respiratory isolates indicates two evolutionarily distinct B. anthina clades. Frontiers in Microbiology, 14 1274280, 1-14. doi: 10.3389/fmicb.2023.1274280

Genomic analyses of Burkholderia respiratory isolates indicates two evolutionarily distinct B. anthina clades

2023

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

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

2023

Journal Article

Differential regulation of natural killer cells by tumor necrosis factor receptors 1 and 2

McCulloch, Timothy R., Rossi, Gustavo Rodrigues, Lam, Allie, Wong, Joshua, Kane, Lawrence P, Herold, Marco, Wells, Timothy and Souza-Fonseca-Guimaraes, Fernando (2023). Differential regulation of natural killer cells by tumor necrosis factor receptors 1 and 2. The Journal of Immunology, 210 (S1), 72.28-72.28. doi: 10.4049/jimmunol.210.supp.72.28

Differential regulation of natural killer cells by tumor necrosis factor receptors 1 and 2

2023

Conference Publication

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

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

2023

Journal Article

IFI27 transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study

Shojaei, Maryam, Shamshirian, Amir, Monkman, James, Grice, Laura, Tran, Minh, Tan, Chin Wee, Teo, Siok Min, Rodrigues Rossi, Gustavo, McCulloch, Timothy R., Nalos, Marek, Raei, Maedeh, Razavi, Alireza, Ghasemian, Roya, Gheibi, Mobina, Roozbeh, Fatemeh, Sly, Peter D., Spann, Kirsten M., Chew, Keng Yih, Zhu, Yanshan, Xia, Yao, Wells, Timothy J., Senegaglia, Alexandra Cristina, Kuniyoshi, Carmen Lúcia, Franck, Claudio Luciano, dos Santos, Anna Flavia Ribeiro, Noronha, Lucia de, Motamen, Sepideh, Valadan, Reza, Amjadi, Omolbanin ... Tang, Benjamin (2023). IFI27 transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study. Frontiers in Immunology, 13 1060438, 1-14. doi: 10.3389/fimmu.2022.1060438

IFI27 transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study

2022

Journal Article

CIS and TGF ‐β regulatory pathways influence immunity to bacterial infection

McCulloch, Timothy R., Rossi, Gustavo R., Schreuder, Jaring, Belz, Gabrielle T., Wells, Timothy J. and Souza‐Fonseca‐Guimaraes, Fernando (2022). CIS and TGF ‐β regulatory pathways influence immunity to bacterial infection. Immunology, 167 (1), 54-63. doi: 10.1111/imm.13516

CIS and TGF ‐β regulatory pathways influence immunity to bacterial infection

2022

Journal Article

Genomic diversity and antimicrobial resistance of Prevotella species isolated from chronic lung disease airways

Webb, Kasey A., Olagoke, Olusola, Baird, Timothy, Neill, Jane, Pham, Amy, Wells, Timothy J., Ramsay, Kay A., Bell, Scott C., Sarovich, Derek S. and Price, Erin P. (2022). Genomic diversity and antimicrobial resistance of Prevotella species isolated from chronic lung disease airways. Microbial Genomics, 8 (2) 000754. doi: 10.1099/mgen.0.000754

Genomic diversity and antimicrobial resistance of Prevotella species isolated from chronic lung disease airways

2022

Journal Article

Inhibition of the master regulator of Listeria monocytogenes virulence enables bacterial clearance from spacious replication vacuoles in infected macrophages

Tran, Thao Thanh, Mathmann, Carmen D., Gatica-Andrades, Marcela, Rollo, Rachel F., Oelker, Melanie, Ljungberg, Johanna K., Nguyen, Tam T. K., Zamoshnikova, Alina, Kummari, Lalith K., Wyer, Orry J. K., Irvine, Katharine M., Melo-Bolívar, Javier, Gross, Annette, Brown, Darren, Mak, Jeffrey Y. W., Fairlie, David P., Hansford, Karl A., Cooper, Matthew A., Giri, Rabina, Schreiber, Veronika, Joseph, Shannon R., Simpson, Fiona, Barnett, Timothy C., Johansson, Jörgen, Dankers, Wendy, Harris, James, Wells, Timothy J., Kapetanovic, Ronan, Sweet, Matthew J. ... Blumenthal, Antje (2022). Inhibition of the master regulator of Listeria monocytogenes virulence enables bacterial clearance from spacious replication vacuoles in infected macrophages. PLoS Pathogens, 18 (1) e1010166, e1010166. doi: 10.1371/journal.ppat.1010166

Inhibition of the master regulator of Listeria monocytogenes virulence enables bacterial clearance from spacious replication vacuoles in infected macrophages

2021

Journal Article

Inferior outcomes in lung transplant recipients with serum Pseudomonas aeruginosa specific cloaking antibodies

Divithotawela, Chandima, Pham, Amy, Bell, Peter T., Ledger, Emma L., Tan, Maxine, Yerkovich, Stephanie, Grant, Michelle, Hopkins, Peter M., Wells, Timothy J. and Chambers, Daniel C. (2021). Inferior outcomes in lung transplant recipients with serum Pseudomonas aeruginosa specific cloaking antibodies. The Journal of Heart and Lung Transplantation, 40 (9), 951-959. doi: 10.1016/j.healun.2021.05.016

Inferior outcomes in lung transplant recipients with serum Pseudomonas aeruginosa specific cloaking antibodies

2021

Journal Article

Anti-LPS IgA and IgG can inhibit serum killing of Pseudomonas aeruginosa in patients with cystic fibrosis

Pham, Amy, Ledger, Emma L., Coggon, Carrie F., Henderson, Ian R., Reid, David W., Bell, Scott C., Smith, Daniel J. and Wells, Timothy J. (2021). Anti-LPS IgA and IgG can inhibit serum killing of Pseudomonas aeruginosa in patients with cystic fibrosis. Infection and Immunity, 89 (12) e00412-21, e0041221. doi: 10.1128/iai.00412-21

Anti-LPS IgA and IgG can inhibit serum killing of Pseudomonas aeruginosa in patients with cystic fibrosis

2021

Journal Article

Towards efficient immunotherapy for bacterial infection

McCulloch, Timothy R., Wells, Timothy J. and Souza-Fonseca-Guimaraes, Fernando (2021). Towards efficient immunotherapy for bacterial infection. Trends in Microbiology, 30 (2), 158-169. doi: 10.1016/j.tim.2021.05.005

Towards efficient immunotherapy for bacterial infection

2021

Journal Article

Mediation of interleukin-23 and tumor necrosis factor–driven reactive arthritis by Chlamydia-infected macrophages in SKG mice

Romand, Xavier, Liu, Xiao, Rahman, M. Arifur, Bhuyan, Zaied Ahmed, Douillard, Claire, Arora Kedia, Reena, Stone, Nathan, Roest, Dominique, Chew, Zi Huai, Cameron, Amy J., Rehaume, Linda M., Bozon, Aurélie, Habib, Mohammed, Armitage, Charles W., Nguyen, Minh Vu Chuong, Favier, Bertrand, Beagley, Kenneth, Maurin, Max, Gaudin, Philippe, Thomas, Ranjeny, Wells, Timothy J. and Baillet, Athan (2021). Mediation of interleukin-23 and tumor necrosis factor–driven reactive arthritis by Chlamydia-infected macrophages in SKG mice. Arthritis and Rheumatology, 73 (7) art.41653, 1200-1210. doi: 10.1002/art.41653

Mediation of interleukin-23 and tumor necrosis factor–driven reactive arthritis by Chlamydia-infected macrophages in SKG mice

2021

Journal Article

BamA and BamD are essential for the secretion of trimeric autotransporter adhesins

Rooke, Jessica L., Icke, Christopher, Wells, Timothy J, Rossiter, Amanda E., Browning, Douglas F., Morris, Faye C., Leo, Jack C., Schütz, Monika S., Autenrieth, Ingo B., Cunningham, Adam F., Linke, Dirk and Henderson, Ian R. (2021). BamA and BamD are essential for the secretion of trimeric autotransporter adhesins. Frontiers in Microbiology, 12 628879, 1-10. doi: 10.3389/fmicb.2021.628879

BamA and BamD are essential for the secretion of trimeric autotransporter adhesins

Funding

Current funding

  • 2024 - 2025
    Counteracting cloaking antibodies to treat intractable Pseudomonas infection.
    Cystic Fibrosis Foundation USA
    Open grant
  • 2024 - 2025
    Evaluation of plasmapheresis to treat intractable lung infections in people with cystic fibrosis
    Cystic Fibrosis Research Limited
    Open grant
  • 2023 - 2025
    Personalising diagnosis and treatment of Pseudomonas aeruginosa infection (NHMRC Ideas Grant administered by Griffith University)
    Griffith University
    Open grant

Past funding

  • 2023 - 2024
    Understanding and counteracting antibody-mediated inflammation driving lung damage
    Conquer Cystic Fibrosis Lung Health Transplant Grant
    Open grant
  • 2022 - 2024
    Antibody mediated exacerbation of Pseudomonas aeruginosa infected chronic wounds (an MSH-RSS administered by MSHHS)
    Metro South Research Support Scheme Co-funded Collaboration Grant
    Open grant
  • 2021 - 2024
    Impact and treatment of cloaking antibodies in Cystic Fibrosis
    Cystic Fibrosis Foundation USA
    Open grant
  • 2019 - 2021
    Paradoxical antibody: the role of antibody in exacerbating Pseudomonas lung infection
    NHMRC Project Grant
    Open grant
  • 2017
    Determining the scope and mechanism of inhibitory antibodies in bacterial lung infections.
    UQ Early Career Researcher
    Open grant

Supervision

Availability

Dr Timothy Wells is:
Available for supervision

Before you email them, read our advice on how to contact a supervisor.

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.

Supervision history

Current supervision

  • Doctor Philosophy

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

    Principal Advisor

  • Master Philosophy

    Antibody mediated exacerbation of Pseudomonas aeruginosa infected chronic wounds

    Principal Advisor

    Other advisors: Professor Kiarash Khosrotehrani

  • Doctor Philosophy

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

    Principal Advisor

    Other advisors: Dr Kate McCarthy

  • Doctor Philosophy

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

    Principal Advisor

    Other advisors: Professor Ian Henderson, Dr Jessica Rooke

  • Doctor Philosophy

    Investigating B cell responses to Pseudomonas O-Antigen

    Principal Advisor

    Other advisors: Professor Ian Henderson

  • Doctor Philosophy

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

    Principal Advisor

    Other advisors: Professor Mark Morrison

  • Doctor Philosophy

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

    Associate Advisor

    Other advisors: Professor Gabrielle Belz

  • Doctor Philosophy

    The role of endoplasmic reticulum stress in spondyloarthropathy

    Associate Advisor

    Other advisors: Professor Ranjeny Thomas, Dr Anne-Sophie Bergot

  • Doctor Philosophy

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

    Associate Advisor

    Other advisors: Professor Antje Blumenthal

Completed supervision

Media

Enquiries

Contact Dr Timothy Wells directly for media enquiries about:

  • cystic fibrosis infections
  • Pseudomonas aeruginosa

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