Ongoing Projects

Project 1: Testing novel liposomal formulations as modulators of bladder pain and inflammation

In collaboration with PD Dr. E. Babyichuk (Institute of Anatomy, University of Bern), we are developing and testing two kinds of lipid-based formulations: liposomal nanotraps, which neutralize membrane-damaging bacterial exotoxins, and LPS-neutralizing liposomes (LNL), which inactivate lipopolysaccharides (LPS) to prevent excessive immune activation. We want to study how their application affects the course of acute and chronic inflammatory responses in the bladder wall, occurring as the result of radiation therapy, chemical exposure or bacterial infection of the bladder.  Our approach presents an innovative, non-antibiotic strategy for pain and UTI management, and paves the way for novel non-antibiotic therapies for UTIs and other toxin-mediated diseases.

Project 2. A biomimetic contractile model of the urinary bladder

Concomitant with the ageing population, the incidence of LUTD is steadily increasing, necessitating more research into the mechanisms of LUTD and development of new therapeutic approaches. Recreating the disease-mediated bladder changes in vitro is challenging because cells put in culture rapidly lose their phenotype, and animal studies, especially in rodents, are limited by differences in bladder function and tissue programs.  In collaboration with Prof. Dr. Yves Perriard and Integrated Actuators Laboratory (LAI), EPFL, Neuchatel, we are developing a tissue-engineered contractile model of the bladder - the “actuated bio-bladder“, recreating normal function and mimicking disease. In the frame of our multi-centre interdisciplinary collaboration, we merge cutting-edge 3D bioprinting, soft actuator technology, fluid and solid mechanics with the existing gene expression profiling data to build a model of the normal and dysfunctional human bladder amendable to experimental control. We are working on a biomimetic bladder model that (i) delivers physiological and disease waveforms; (ii) enables co-cultures on/through electrodes (porous); (iii) supports imaging (transparent); (iv) provides self-sensed, closed-loop strain/force; (v) multiplexes in standard incubators with embedded power supply; and (vi) demonstrates functional barrier and contractile behavior with human cells, including immune components.

Project 3: Urinary exosomes as a source of protein and microRNA-based disease biomarkers

Urine is easy to collect non-invasively and contains extracellular vesicles including exosomes, which can be used as disease biomarkers.  Urinary miRNA assessment offers advantages over urodynamics and other methods, requiring special skills and trained personnel. In order to facilitate the assessment of the bladder function, relevant for diagnostic of LUTS and obstruction, we developed an optimized ultracentrifugation and size exclusion chromatography approach for highly reproducible isolation for 50-150 nm urinary vesicles, corresponding to the exosomes, from urine. As a part of the Center for Extracellular Vesicle Research (EVR) at the University of Bern, we are investigating the composition and content (proteins, non-coding RNAs including miRNAs) of the urinary extracellular vesicles purified from normal and patients’ urine.  Our panel of representative miRNAs is explored to develop a non-invasive diagnostic test for bladder outlet obstruction and neurogenic bladder dysfunction.

Comparative transcriptome and proteome analysis of SCI-induced neurogenic LUTD in humans and rats

Project 4. Effect of early treatment with Onabotulinumtoxin A on the bladder function of patients with acute SCI in single cell resolution

Despite the ample evidence of the beneficial effect of BoNTA on the bladder function in SCI patients, there is a limited understanding of the mechanisms by which BoNTA affects specific cell types in the bladder wall and regulates the expression of different genes, proteins and metabolites, preventing neurogenic detrusor overactivity (NDO). Using the biopsies and urine collected by our collaborators from Sunnaas Hospital and Oslo University Hospital, Norway, we carried out a longitudinal study of the molecular changes in the bladders of SCI patients, receiving BoNTA or placebo shortly after injury and at a 3 months’ time-points afterwards. We analyzed bulk and single nuclei transcriptomes from the bladder biopsies of SCI patients, and carried out urinary proteomics. Our results show that early BoNTA injections into the bladders of SCI patients preserved organ architecture, effectively preventing immune cell infiltration and urothelial dysfunction leading to NDO. Urine collection and analysis are valuable tools in the evaluation of bladder (dys)function and treatment efficacy.