On June 12th 2024 Elena Sendino Garví successfully defended her thesis entitled “CRISPRing the way to Advanced in Vitro Modelling for Genetic Kidney Disease” at Utrecht University. The project was co-funded by Health~Holland, Top Sector Life Sciences & Health and supervised by Dr. Manoe Janssen and Prof. Dr. Roos Masereeuw.
Chronic kidney disease (CKD) affects 1 out of 8 people of the global population and it is the 10th cause of death worldwide. In children and young adults CKD is frequently caused by genetic defects but how these mutations contribute to kidney disease is often not known.
In this research Elena has developed advanced in vitro disease models of several genetic kidney diseases to 1) better understand whether a candidate gene is directly causing the phenotype, 2) further evaluate the pathophysiological mechanisms of the disease, and 3) provide a platform for target discovery and drug screening. To study transport and leakage in cystinosis she created 3D culture models in which kidney proximal tubular cells are cultured and perfused on a hollow fiber membrane or grown on a hollow gel tube. Furthermore, she created CRISPR/Cas induced knockouts in induced pluripotent stem cells (iPSCs) to develop disease kidney organoids. In this way we could study the effect of NPHP1 and KCNJ16 loss in kidney organoids to better understand disease pathology and screen for potential therapeutic compounds. Finally, Elena explored the potential of CRISPR/Cas gene repair as a therapy for a genetic kidney disease to offer a novel potential therapeutic approach for nephropathic cystinosis.
