Projects / Programmes
Differentiation of urothelial cells
January 1, 2018
- December 31, 2027
| Code |
Science |
Field |
Subfield |
| 3.03.00 |
Medical sciences |
Neurobiology |
|
| Code |
Science |
Field |
| B000 |
Biomedical sciences |
|
| Code |
Science |
Field |
| 3.01 |
Medical and Health Sciences |
Basic medicine |
Cell biology, urology, urothelium, urinary bladder, differentiation, regeneration, vesicular traffic, exocytosis, endocytosis, cell junctions, cell signalling, vitamin A, amniotic membrane extracellular vesicles, cystitis, cancer, electron microscopy, correlative microscopy, tissue engineering
Data for the last 5 years (citations for the last 10 years) on
April 18, 2024;
A3 for period
2018-2022
| Database |
Linked records |
Citations |
Pure citations |
Average pure citations |
| WoS |
348 |
7,392 |
5,786 |
16.63 |
| Scopus |
341 |
8,240 |
6,521 |
19.12 |
Researchers (26)
Organisations (1)
Abstract
Research programme P3-0108 “Differentiation of urothelial cells” is running continuously since 1999. The proposed programme deals with important research challenges in the field of cell biology and the most appealing problems of modern urology, which represents huge social and economic burden in Slovenia and in the world. Since the financing of basic and applicative research is constantly underfunded worldwide, the progress in prevention, diagnostics and treatment of frequent urologic disorders is modest in comparison to other fields of medicine.
Normally differentiated urothelium establishes blood-urine barrier by vesicular traffic and intercellular communication. New findings indicate that the urothelium also has sensory function. The urothelium is extremely stable tissue within healthy urinary bladder. Nevertheless, it has great capacity of regeneration after injuries that disrupt blood-urine barrier. This regeneration can follow divergent pathways. It could lead to complete regeneration, but also to incomplete regeneration or even uncontrolled regeneration. Incomplete and uncontrolled regeneration often lead to the development of cystitis and urinary bladder cancer, respectively.
The objectives of proposed research programme are to investigate and understand cell and molecular mechanisms, which lead towards normal differentiation of urothelial cells, and those that lead to urinary bladder diseases (e.g. cystitis, cancer).
Aims of the programme are:
1) Analysis of vesicular traffic in urothelial cells. We will explore mechanisms of plasma membrane formation and micropinocytosis during terminal differentiation of urothelial cells and during complete, incomplete and uncontrolled regeneration.
2) Analysis of intercellular communications in the urinary bladder. We will determine the role of retinoid signalling pathway, intercellular interactions and extracellular vesicles during cystitis development and during urothelial carcinogenesis. We will investigate the role of receptors and ion channels in the functioning of the urinary bladder.
3) Development of advanced electron microscopy methods and other state-of-the-art microscopic methods and optimisation of tissue-engineering methodology. The results of this objective will facilitate towards the improved realisation of other objectives of our programme and will be available to a wider scientific community (Graphical abstract-DUC_2018_ang.pdf).
The programme is ambitious, but it is well justified by our previous results. Since we investigate basic cell processes by using different animal models and in vitro models, which mimic the processes within human urothelium, as well as human samples, we will be able to obtain complex insight into the mechanisms of the urinary bladder disease progress. Our research will therefore contribute to new insights in basic science, and will have impact on health care through the development of potential therapeutic targets and innovative treatment strategies for different urinary bladder diseases.
Significance for science
The programme fit into the broad spectrum of currently important areas of cell biology. Our main research topics are vesicular traffic and cell communications, which both play a critical role in cell differentiation. As divergent pathways lead to different diseases, our research topics answer many questions in medicine.
In the area of urothelial cell biology our group is well recognised in the world, as demonstrated by citations of our published work, invited talks and continuous cooperation with world leading groups (Tung-Tien Sun, University of New York, USA, Matthew Mulvey, University of Utah, USA and Jennifer Southgate, University of York, Great Britain).
Investigations of human urinary bladder samples (cooperation with Department of Urology, University Medical Centre Ljubljana) enable the translation of basic cell biology knowledge to better understanding of urothelium-related diseases (cystitis, bladder cancer).
We continuously develop and use new in vivo and in vitro models of urothelial differentiation, regeneration and diseases. These give us the opportunity of studying the effects of therapeutics on diseased urothelium.
We develop urothelial substitutes, which is an important contribution to the tissue engineering progress. Urothelial (and urinary bladder) grafts could improve treatment of many urologic disorders.
In the field of nanomedicine, we develop systems for targeted drug delivery of nanoparticles. We explore mechanisms of action of chitosan, which is a promising substance for bacterial cystitis treatment.
We are introducing and developing new methods of electron microscopy, which contribute to improved quality of our results.
Significance for the country
The research programme Differentiation of urothelial cells contributes to promote Slovenia in the world with publications in distinguished international journals (such as Histochemistry and Cell Biology, Molecular Biology of the Cell, Journal of Cell Biology, Biology of the Cell, The Journal of Infectious Diseases), invited talks at international congresses and at foreign universities.
With the realization of our programme, we want to achieve practical goals. Our basic studies are designed in a way that they address most relevant issues in urology, which impact quality of life and the represent big economic burden. The most challenging of them are the recurrence of superficial papillary tumours, deficient urothelial substitutes in reconstructive urology, chronic bacterial cystitis and inadequate treatment of interstitial cystitis/bladder pain syndrome and overactive bladder.
Our work on tissue engineering and studies of nanoparticles could contribute to more efficient and cheaper treatments in urology.
Members of the programme group run courses for undergraduate and postgraduate students. They are authors of university textbooks and other study materials. Members of the programme group are mentors to undergraduate and postgraduate students. Together, these enables the transfer of up-to-date and most relevant achievements in cell biology to students.
Members of the programme group appear in public media with discussions and as propagators of science.
Members of the programme group hold patents.
At the Institute of Cell Biology, where the programme is based, we runs projects for pharmaceutical company (Lek d.o.o.).
Young researchers are included in our programme. Young researchers, who had successfully finished their postgraduate studies, were employed either as teaching staff at University of Ljubljana or as researchers.
The important part of our work is dedicated to implementation and development of electron microscopy methods for life sciences. We provide these methods and expertise to other groups and scientists.
Most important scientific results
Interim report
Most important socioeconomically and culturally relevant results
Interim report
