Peter van Mourik

CONTENTS Chapter 1 General Introduction 7 Chapter 2 R117H-CFTR function and response to VX-770 correlate with mRNA and protein expression in intestinal organoids 19 Chapter 3 Potentiator synergy in rectal organoids carrying S1251N, G551D or F508del CFTR mutations 39 Chapter 4 Protocol for application, standardization and validation of the forskolin induced swelling assay in Cystic Fibrosis human colon organoids 67 Chapter 5 Centralized intestinal organoid generation is a feasible and safe approach for personalized medicine as demonstrated in the European HIT-CF study 119 Chapter 6 Comparison of organoid swelling and in vivo biomarkers of CFTR function to determine effects of lumacaftor-ivacaftor in patients with Cystic Fibrosis homozygous for the F508del mutation 129 Chapter 7 Rectal organoids enable personalized treatment of Cystic Fibrosis 139 Chapter 8 Rationale and design of the HIT-CF organoid study: stratifying Cystic Fibrosis patients based on intestinal organoid response to different CFTR- modulators 163 Chapter 9 General discussion 179 Chapter 10 Nederlandse samenvatting 203 Chapter 11 Addendum 213