Islet Biology

Dr. Carina (Kaiyuan) Yang - Postdoc

Mireia Molina van den Bosch - PhD Student

A comprehensive understanding of embryonic pancreas development is essential to reveal the precise mechanisms underlying pancreatic cell fate commitment.

Our group utilizes the pig, a large animal model which resembles human physiology and anatomy, to perform cross-species comparisons of embryonic pancreas development against human and mouse. We aim to:

* identify species distinct/conserved factors directing pancreatic cell fates; and

* verify targets for specific/efficient endocrine/β-cell formation using transgenic pig models and pig iPSC differentiation systems.

Dr. Joane vanVuuren - Postdoc

Priyadharishini Ayyappan - PhD student

β-cell regeneration and replacement offer the possibility of a permanent cure for diabetes. However, to understand human pancreatic development, promote β-cell regeneration, and/or modulate metabolic stresses, it is necessary to identify and target specific pancreatic cell types.

We therefore generated a large panel of monoclonal antibodies against all human pancreatic cell types, including the β-cells. With these novel antibodies, we aim to:

* isolate pancreatic cell-types and their different subtypes from donor material for in-depth characterization to better understand cell-type specific phenotypes

* identify markers of pancreatic cell type heterogeneity during diabetes progression that can function as a target for cell-type specific therapy

* enrich stem-cell derived endocrine progenitors during differentiation to enhance maturation and thus increase their potential for cell replacement therapy

* develop antibody-conjugated drug therapy that specifically targets resident β-cells for regeneration as well as protection against ER stress-induced cell death.

Dr. Christos Karampelias - Postdoc

To preserve and regenerate pancreatic β-cells, insights into the molecular pathways involved in the pathological loss of β-cells is necessary.

Therefore, we investigate the transcriptional and proteomic alterations in the pancreas during diabetes and metabolic stress progression. Healthy and diabetic pig models with traceable β-cells via GFP reporter provide powerful in vivo models. Further, we established 3D pancreatic organoid culture system to aid the validation and screen in vitro for potential targets to alleviate β-cell failure and promote β-cell regeneration.

Furthermore, we will examine the potential of ductal cells in the porcine pancreas as a stem-like cell population to generate β-cells. We will combine single-cell technologies with organoid cultures and chemical screening approaches to characterize ductal cells and identify novel pathways driving β-cell neogenesis