-
Medical and health sciences
- Molecular and cell biology not elsewhere classified
Autosomal dominant polycystic kidney disease (ADPKD) occurs upon mutations in either the PKD1 or PKD2 gene and represents the most common monogenetic disease (incidence 1:500-1:1000). Frequent and dire complications of APDKD are cardiovascular anomalies, such as intracranial aneurysms, which upon rupture are life-threatening. Here, I intend to further exploit a CRISPR/Cas9-mediated animal model for ADPKD to obtain morphological, molecular and functional insights into the cardiovascular complications of ADPKD. For this, we will identify these anomalies in three-dimensions within the Xenopus tadpole using cutting-edge light sheet microscopy and deep learning image processing. Next, we will use multi-omic approaches to gain deeper insights into the cell states/gene signatures that drive these pathologies, thus elucidating the underlying molecular mechanisms. Finally, we intend to leverage this knowledge to explore new treatment strategies, by modulating the pathologies, both genetically and chemically. We expect this work to lead to a better understanding of the cardiovascular manifestations of ADPKD providing fundamental and translational insight impacting therapeutic strategies.