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Helmholtz Munich | J. vanVuuren (left), C. Yang (middle), C. Karampelias (right)

Islet Biology

We study the molecular basis of pancreatic lineage specification as well as islet cell development, maturation, heterogeneity, function, and regeneration across species. We investigate epigenetic, transcriptional, and proteomic features in mouse, pig, and human islets in order to uncover and functionally interrogate the driving factors and molecular programs behind the changes in islet cell phenotypes.

We study the molecular basis of pancreatic lineage specification as well as islet cell development, maturation, heterogeneity, function, and regeneration across species. We investigate epigenetic, transcriptional, and proteomic features in mouse, pig, and human islets in order to uncover and functionally interrogate the driving factors and molecular programs behind the changes in islet cell phenotypes.

Research Topics

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

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

Who we are

Dr. Kaiyuan Yang

Post Doc - Islet Biology

Dr. Joanne van Vuuren

Post Doc - Islet Biology

Dr. Christos Karampelias

Postdoc - Islet Biology

Mireia Molina van den Bosch

PhD Student - Islet Biology and Intestinal Stem Cell Research

Ines Kunze

Technical Assistant - Intestinal stem cells

Kerstin Diemer

Lab Manager IDR-L and technical assistant - Islet Biology

Priyadharishini Ayyappan

PhD Student - Islet Biology

Publications

Read more

2021 Scientific Article in Nature metabolism

Müller, J.A. ; Groß, R. ; Conzelmann, C. ; Krüger, J. ; Merle, U. ; Steinhart, J. ; Weil, T. ; Koepke, L. ; Bozzo, C.P. ; Read, C. ; Fois, G. ; Eiseler, T. ; Gehrmann, J. ; van Vuuren, J. ; Wessbecher, I.M. ; Frick, M. ; Costa, I.G. ; Breunig, M. ; Grüner, B. ; Peters, L. ; Schuster, M. ; Liebau, S. ; Seufferlein, T. ; Stenger, S. ; Stenzinger, A. ; MacDonald, P.E. ; Kirchhoff, F. ; Sparrer, K.M.J. ; Walther, P. ; Lickert, H. ; Barth, T.F.E. ; Wagner, M. ; Münch, J. ; Heller, S. ; Kleger, A.

SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas.

Contact

Donna Thomson

Personal Assistant IDR-L / Office and Administrative Project Manager

Campus Neuherberg, building 3620, room 306b