PhD degree for Eric Verschuren

11 February 2020

Eric Verschuren successfully defended his thesis entitled "The sense of urinary flow in kidney physiology".

Outline of this thesis
The aim of this thesis is to characterize how pro-urinary flow in the tubular system of the kidneys orchestrates ion transport to guarantee electrolyte and water homeostasis. Elucidating the mechanisms behind this fascinating phenomenon may pave the way for the development of novel therapeutics for diseases where pro-urinary flow or sensing thereof are defective. In detail, and in the context of disease, this thesis aims to provide new insights into the molecular signaling pathways affected by pro-urinary flow that may also be key to ADPKD. In chapter 2, the role of PC1 in Mg2+, Ca2+ and water handling in the kidneys was studied in a pre-cystic kidney-specific inducible Pkd1 knockout mouse model. Subsequently, the role of PC1 in the regulation of Mg2+ handling was studied at the level of the transcriptome, in chapter 3, where DCT was isolated from inducible Pkd1 knockout mice using the COPAS technology. Next, chapter 4 aimed to provide new insights into the molecular mechanisms involved with pro-urinary flow and Mg2+ transport. State-of-the-art CRISPR/Cas9 technology and microfluidics, applied in vitro, revealed tubular flow as a new factor activating Mg2+ transport
in DCT, independent of the primary cilium. In chapter 5, in vitro microfluidics experiments were combined with studies in mouse and zebrafish, to obtain new insights into how pro-urinary flow could affect renal ATP release into the nephron lumen in health and disease (i.e. ADPKD). In chapter 6, the involvement of the purinergic receptor P2Y1 in renal electrolyte handling was studied in the zebrafish model. Finally, the main findings of this thesis are summarized in chapter 8 and discussed in chapter 7 to highlight the impact of this thesis.

Click here to access Eric' thesis digitally.