Abdominal Area, Kidneys & Pelvis

Modelling Johanson-Blizzard syndrome (JBS) in a dish – molecular insights into UBR1 deficiency using pluripotent stem cell-derived pancreatic organoids

Institution: Institute of Molecular Oncology and Stem Cell Biology
Applicant: Markus Breunig
Funding line:
First and Second Applications

Johanson-Blizzard syndrome (JBS) is caused by homozygous mutations in the UBR1 gene, encoding for an E3 ubiquitin protein ligase and therefore directly regulating the degradation of multiple proteins. Despite the identification of the genetic cause, the exact mechanism leading to the prenatal loss of pancreatic cells and other tissues has remained elusive. In my innovative JBS model, patient-specific human pluripotent stem cells will be differentiated to mature pancreatic cells by addition of specific growth factors. Hereby, I cannot only describe the predominantly affected cell type and route of cell death, but can also determine disease-causing substrates, thereby enabling the development of future therapeutic concepts.