UroAgeMAP - Identifying cellular and molecular determinants of urothelial-to-mesenchymal crosstalk in aged patients

• Applicant: Privatdozentin Dr. Jennifer Kranz
• Subject Area: Reproductive Medicine, Urology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 511931150

Infections and cancerogenesis represent hallmarks of ageing. Urinary tract infections and urothelial carcinoma impose tremendous health problems to the elderly. In women, the prevalence of urinary tract infections increases with age, and doubles reaching approximately the rate in the general female population above the age of 65 years. Nearly half of the affected elderly patients suffer from recurrent urinary tract infections, leading to repeated hospitalizations and a tremendous socio-economic burden. Currently, antibiotic treatment represents the “gold-standard” therapy, whereas personalized approaches that target the urothelium's regenerative capacity are missing. The incidence of bladder cancer correlates with increased age in both sexes. Urothelial carcinoma, the second most common urological malignancy, is responsible for 5% of all cancer-related deaths in the US. Several ageing-related pathomechanisms of cancerogenesis of urothelial cells have been proposed, including stem-cell exhaustion and genomic instability. Especially the dynamics of urothelial cell plasticity and the role of the tumor-supportive stroma have been investigated as important determinants of the local tumour microenvironment. While risk genotypes, e.g. a TLR4 polymorphism, related to recurrent urinary tract infection and nitrosamine exposure for urothelial cancer development have been identified, a detailed understanding of the molecular changes associated with ageing of the urothelial cell niche is currently lacking. Therefore, there is an urgent unmet medical need to better understand the molecular changes of the urothelial-cell niche in ageing using state of the art technologies, guiding the development of novel diagnostics and targeted therapeutics. UroAgeMAP proposes a set of experiments using cutting-edge spatial transcriptomics technologies to unravel the molecular heterogeneity of the urothelial-to-mesenchymal crosstalk associated with ageing in humans.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Christoph Kuppe