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Project

Endoplasmic reticulum and mitochondria: common drivers of human β cell and neuronal fate (PANDAROME)

Diabetes and brain disorders appear at first glance to be completely different diseases. However, human
genetics has unveiled some severe forms of diabetes in babies that are associated with abnormal brain
development, including small brain size and epilepsy. Intriguingly, the mutations causing these diseases hit
genes with a role in two critical organelles: the endoplasmic reticulum and mitochondria, which together control
the production of protein and energy in our cells. These mutated genes are active in many organs of the
patients, but the only two cell types that are affected are insulin-producing pancreatic β cells and brain neural
cells. This strongly suggests a shared sensitivity of these two cell types to organelle stress, but how can we
explain this and how can we fix it in affected patients? Our project PANDAROME (for PAncreatic and Neuronal
Development Altered by Re-Organization of Mitochondria and ER dynamics) aims to unravel the role of these
organelles in pancreas and brain development, and how their disruption causes diseases. We will use
innovative human stem cell models and humanized mouse models, to assess how organelles instruct the fate
of β cells and neurons during development and life, and to identify treatments that rescue cell defects. As our
focus on patient mutations and cells ensures relevance to human disease, we anticipate to uncover new
avenues to treat diabetes and brain development diseases.

Date:1 Jan 2022 →  Today
Keywords:diabetes, epilepsy, microcephaly, endoplasmic reticulum stress, unfolded protein response, mitochondria, differentiation, neuron
Disciplines:Endocrinology