Urological Biology and Cancer

Our work

Bladder diseases have been historically understudied. We look at two key areas: recurrent / treatment-resistant urinary tract infection (UTI) and urothelial cancers. Both have suffered from a lack of human cell-based models to provide insights that experimental animals cannot.

In addition to studying the basic biology, we build innovative new microtissue models and develop novel therapies, in broad interdisciplinary collaborations across cell biology, microbiology, computational genetics, medicine, biomedical engineering, materials science and mathematics, spanning academia, industry and the clinic.

Research themes include:

• Tissue engineering and on-chip microfluidic platforms
• Molecular human cell biology
• Host / pathogen interactions of recurrent UTI in various populations, including older individuals and immunosuppressed renal transplant patients
• Antimicrobial resistance
• Pathogen genomic variation in vivo, including within the urinary microbiota
• Biofilms
• Novel drug delivery systems
• Epithelial innate immunity, urothelial biology and urothelial cancers.

Host-pathogen interactions

Urinary tract infection (UTI) is caused by a broad variety of different microbes. We are interested in how bacterial behaviours at the host/pathogen interface facilitate virulence and persistence at the cellular and molecular level, focusing on a number of different pathogens including Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, Proteus mirabilis and Pseudomonas aeruginosa, among others. We study various bacterial behaviours, and are particularly intrigued by the phenomenon of invasion, whereby bacteria shelter inside cells in the bladder wall to form stubborn reservoirs that resist treatment. Given that many of the same species can be isolated from healthy bladders as part of the normal bladder "microbiome", we want to understand what characteristics distinguish the pathogens from their more friendly counterparts, and how the two camps interact. Finally, the host generally has many ways to counter invading bacteria, but this is not well studied in human cells in the UTI context.

Treatment failure and resistance

It is well known that 20-30% of UTIs come back even despite treatment, and the bacteria have evolved a number of tricks to evade antibiotics. Even bacteria that can be killed by a particular antibiotic in a test tube can thrive in the body, at least temporarily but long enough to regroup, in high doses of drug by switching on emergency genetic programmes (a phenomenon known as ‘phenotypic resilience’). Using more physiological human microtissue models, we aim to use the science of transcriptomics, proteomics and metabolomics to pinpoint how UTI bacteria escape killing under these circumstances, which could lead to novel drug targets or alternative therapies. We are also studying biofilms, which are naturally treatment-resistant communities of microbes, often comprised of multiple species, that are problematic in a variety of chronic infections but are not as well understood in UTI. 

Human microtissue models

While many significant advances have been made in animal models, there are key species-specific differences in urinary tract structure, function and immunity whose consequences for patient relevance are unknown. In recent years, we have developed innovative human urothelial microtissue models to understand bladder biology. The most recent version, called 3D-UHU, is fully stratified to human thickness (up to 7-8 layers, as opposed to the mouse urothelium, which only expresses three); is terminally differentiated with correct biomarkers; has robust barrier function; and is fully urine-tolerant, allowing the exposure of bacteria or materials in their native environment. 3D-UHU also elaborates a protective glycosaminoglycan layer on the luminal side, secretes key cytokines in response to infection and undergoes physiological cell shedding, which is a well-known bladder defence mechanism. This in turn disrupts urothelial barrier function, which is a dangerous situation for the host.

3D-UHU underpins many of our infection studies in the lab. We are also adapting the model so it experiences flow and stretch, two important mechanical activities in the bladder, and incorporating catheter material as a model for catheter-induced UTI, a serious problem globally. Because UTI involves a journey from the gut to the bladder, and sometimes from bladder to kidney, we are creating a linked “pelvis-on-a-chip” comprised of individual organoid-based microtissues to study ascending infection. Finally, we have adapted the model as a testbed for understanding urothelial cancers and trialling new treatments for this highly pervasive malignant disease.

Novel therapies

We collaborate with engineering colleagues at UCL and Oxford to develop new cures for UTI and bladder cancer, based on increasing the tissue penetration of existing drugs. One of our collaborative candidates is being taken forward by the UCL spinout company AtoCap Ltd. We are also performing fundamental research to discover entirely new drug targets.

Our experts

Group members

Selected Publications

1. Flores C, Ling J, Loh A, Garcia Maset R, Aw A, White IJ, Fernando R, Rohn JL (2023). A human urothelial microtissue model reveals shared colonization and survival strategies between uropathogens and asymptomatic bacteria. BioRxiv.
2. Stride E, Choi V, Carugo D, Rohn JL, Stoodley P (2023). Drug delivery strategies for antibiofilm therapy. Nature Reviews Microbiology.
3. Jafari NV, Rohn JL (2023). An immunoresponsive three-dimensional urine-tolerant human urothelial (3D-UHU) model to study urinary tract infection. Frontiers in Infection Cell Microbiology, 13, 269.
4. Lasri Doukkali A, Lorenzi T, Parcell BJ, Rohn JL, Bowness R (2023). A hybrid individual-based mathematical model to study bladder infections. Frontiers in Applied Mathematics and Statistics, 9.
5. Morris CJ, Rohn JL, Glickman S, Mansfield KJ (2023). Effective Treatments of UTI - Is Intravesical Therapy the Future? Pathogens, 12 (3).
6. Sathiananthamoorthy S, Florman K, Richard D, Cheng KK, Torri V, McCaig F, Harber M & Rohn JL (2022). Application of various techniques to gain insights into the complex urinary tract microbial communities of renal transplant recipients. Transplant Direct. 2023 Jan 6;9(2):e1418.
7. Aydogdu MO, Rohn JL, Jafari, NV, et al (2022). Severe Acute Respiratory Syndrome Type 2-Causing Coronavirus: Variants and Preventive Strategies. Advanced Science.
8. Jafari NV, Rohn JL (2022). The urothelium: a multi-faceted barrier against a harsh environment. Mucosal Immunology, 15, 1127-1142.
9. Tandogdu Z, Collins J, Shaw G, Rohn JL, et al (2021). Management of patients who opt for radical prostatectomy during the COVID-19 pandemic: An International Accelerated Consensus Statement. BJU Int. 2021 Jun;127(6):729-741.
10. Murray BO, Flores C, Williams C, Flusberg DA, Marr EE, Kwiatkowska KM ... Rohn JL (2021). Recurrent Urinary Tract Infection: A Mystery in Search of Better Model Systems. Front Cell Infect Microbiol. 2021 May 26;11:691210.
11. Kasivisvanathan V, Lindsay J, Rakshani-Moghadam S, Elhamshary A ... Rohn, JL, et al (2020). A cohort study of 30 day mortality after NON-EMERGENCY surgery in a COVID-19 cold site. International Journal of Surgery, 84 57-65.
12. Collins L, Sathiananthamoorthy S, Rohn JL, Malone-Lee, J (2020). A revalidation and critique of assumptions about urinary sample collection methods, specimen quality and contamination. Int Urogynecol J, Jun;31(6):1255-1262.
13. Lau W, Rohn JL, Dharmasena D, Horsley H, Jafari N ... Rohn JL (2020). Novel antibiotic-loaded particles conferring eradication of deep tissue bacterial reservoirs for the treatment of chronic urinary tract infection. Journal of Controlled Release, Dec 10;328:490-502.
14. King JS, Humphreys D, Rohn JL, et al (2020). The great host-pathogen war: UK cellular microbiology meeting 2020. Cellular Microbiology, e13248.
15. Hubbard ATM, Jafari NV, Feasey N, Rohn JL, Roberts AP (2019). Effect of Environment on the Evolutionary Trajectories and Growth Characteristics of Antibiotic-Resistant Escherichia coli Mutants. Frontiers in Microbiology, 10.
16. Katsakouli C, Jiang X, Lau WK, Rohn JL, Edirisinghe M (2019). Generating Antibacterial Microporous Structures Using Microfluidic Processing. ACS Omega, 4 (1), 2225-2233.
17. Rohn JL, Mostowy S, King JS, et al. (2019). The UK Cellular Microbiology Network: Exploring the host-bacterial interface. Cell Microbiol, e13081.
18. Horsley H, Owen J, Carugo D, Malone-Lee J, Stride E, Rohn JL (2019). Ultrasound-activated microbubbles as a novel intracellular drug delivery system for urinary tract infection. Journal of Controlled Release, 301, 166-175.
19. Sathiananthamoorthy S, Malone-Lee J, Gill K, Tymon A ... Rohn JL (2019). Reassessment of routine midstream culture in diagnosis of urinary tract infection. J Clin Microbiol, 57(3):e01452-18.
20. Horsley H, Dharmasena D, Malone-Lee J, Rohn JL (2018). A urine-dependent human urothelial organoid offers a potential alternative to rodent models of infection. 1238 Scientific Reports.

Collaborators

• Prof Eleanor Stride, Institute of Biomedical Engineering, University of Oxford
• Dr Dario Carugo, Institute of Biomedical Engineering, University of Oxford
• Dame Fiona Powrie, Kennedy Institute of Rheumatology, University of Oxford
• Prof Jamie Davies, Centre for Discovery Brain Sciences, University of Edinburgh
• Prof Meriem El Karoui, Centre for Synthetic and Systems Biology, University of Edinburgh
• Prof Mohan Edirisinghe, Department of Mechanical Engineering, UCL
• Prof Francois Balloux, Genetics Institute, UCL
• Dr Lucy Van Dorp, Genetics Institute, UCL Prof Rik Bryan, University of Birmingham
• Prof Mark Linch, UCL Cancer Institute, and Consultant Medical Oncologist, UCLH
• Dr Ruth Bowness, Department of Mathematical Sciences, Univeristy of Bath
• Mr John Hines, Consultant Urological Surgeon, UCLH
• Dr Brett Eisenberg, The Charles Stark Draper Laboratory, Boston USA
• Dr Adam Roberts, Liverpool School for Tropical Medicine.

Related courses

Our members contribute to the MBBS, iBSc, BSc and master's degrees within the Division of Medicine. We provide BSc, iBSc and MSc/MRes research project supervision. We also have an established track record in providing high-quality training to PhD students interested in basic, translational, and clinical research in urological biology.

For patients

If you are a patient or member of the public interested in recurrent, chronic or treatment-resistant UTI, the Chronic UTI Campaign UK is an excellent source of information.