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.
Right – pig embryonic pancreas_SOX9 (Trunk cells, white),
Ecad (epithelial cell surface protein, blue), and endocrine cells(mScarlet reporter, red)
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
White - Ecad
Green – Insulin
Team Leader Islet Biology
Marie Curie Fellow - Team Leader Islet Biology
PhD Student Islet Biology
TA Single Cell Genomics and Intestinal Stem Cells Research
Lab Manager IDR
PhD Student Islet Biology
Doctoral Researcher
Publications
Karampelias, C. ; Yang, K. ; Farkas, F. ; Sterr, M. ; Molina van Den Bosch, M. ; Renner, S. ; Fuß, J. ; von Toerne, C. ; Franzenburg, S. ; Kin, T. ; Wolf, E. ; Kemter, E. ; Lickert, H.
Benchmarking porcine pancreatic ductal organoids for drug screening applications.Yang, K. ; Spitzer, H. ; Sterr, M. ; Hrovatin, K. ; de la O, S. ; Zhang, X. ; Setyono, E.S.A. ; Ud-Dean, M. ; Walzthoeni, T. ; Flisikowski, K. ; Flisikowska, T. ; Schnieke, A. ; Scheibner, K. ; Wells, J.M. ; Sneddon, J.B. ; Kessler, B. ; Wolf, E. ; Kemter, E. ; Theis, F.J. ; Lickert, H.
A multimodal cross-species comparison of pancreas development.Dahiya, S. ; Saleh, M. ; Rodriguez, U.A. ; Rajasundaram, D. ; R. Arbujas, J. ; Hajihassani, A. ; Yang, K. ; Sehrawat, A. ; Kalsi, R. ; Yoshida, S. ; Prasadan, K. ; Lickert, H. ; Hu, J. ; Piganelli, J.D. ; Gittes, G.K. ; Esni, F.
Acinar to β-like cell conversion through inhibition of focal adhesion kinase.Kalla, D. ; Flisikowski, K. ; Yang, K. ; Sangüesa, L.B. ; Kurome, M. ; Kessler, B. ; Zakhartchenko, V. ; Wolf, E. ; Lickert, H. ; Saur, D. ; Schnieke, A. ; Flisikowska, T.
The missing link: Cre pigs for cancer research.Kemter, E. ; Müller, A. ; Neukam, M. ; Ivanova, A. ; Klymiuk, N. ; Renner, S. ; Yang, K. ; Broichhagen, J. ; Kurome, M. ; Zakhartchenko, V. ; Kessler, B. ; Knoch, K.P. ; Bickle, M. ; Ludwig, B. ; Johnsson, K. ; Lickert, H. ; Kurth, T. ; Wolf, E. ; Solimena, M.
Sequential in vivo labeling of insulin secretory granule pools in INS-SNAP transgenic pigs.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
