Team Member

Dr. Katharina Scheibner
Junior group Leader Beta cell replacement

Phone: + 49 89-3187-43167
E-mail
Building/Room: Campus Neuherberg, building 3620, room 028b

 

Human stem cell-derived islets for cell replacement therapy

Diabetes mellitus is one of the most prevalent metabolic diseases worldwide and is characterized by insulin deficiency that is caused by dysfunction or destruction of insulin-producing beta cells in the islet of Langerhans.  Daily insulin administrations saves the life of type 1 diabetic patients, however these patients still suffer from fluctuating blood glucose levels that bear the risk of hypoglycemia, lifelong secondary complications and a shortened life span. Importantly, upon transplantation of cadaveric human islets, patients achieve normoglycemia, however compatible human islets are scarce. Human pluripotent stem cells (hPSCs) serve as an optimal source - due to their self-renewing capacity and potency to differentiate into all cell lineages - to generate endocrine islet cells, such as beta cells, in vitro for cell replacement therapy. 

For this reason, the transplantation of stem cell-derived human islets (SC-islets) hold great promise to cure diabetes. Although the efficiency of recent in vitro differentiation protocols improved, the SC-islets consist of not only endocrine cells but also unwanted non-endocrine cell types that impair functionality of SC-islets and safety for patients. We are specifically interested to develop new approaches to generate advanced SC-islets with improved functionality that eventually permits their transplantation into type 1 diabetic patients. 

Moreover, the molecular mechanisms of human pancreas development, such as the induction and patterning of the endoderm and the foregut as well as the induction of an endocrine fate, are not fully resolved. In vitro differentiation of hPSCs allows us to study these developmental processes in more detail. Therefore, another interest of our group is to unravel these mechanisms and thereby improve in vitro differentiation protocols for cell replacement therapy. 

Academic and Research Activities

Since 2021         Junior Group Leader "Beta cell replacement" 

2020           Post Doc, Institute of Diabetes and Regeneration Research, Helmholtz Centre Munich

2015-2020  PhD student, Institute of Diabetes and Regeneration Research, Helmholtz Centre Munich

2013-2015  Master of Science in Biological Sciences, Westfälische Wilhelms-University of Münster Thesis: “The role of epithelial to mesenchymal transition during mouse endoderm development.” Institute of Diabetes and Regeneration Research, Helmholtz Centre Munich

2014                  Icahn School of Medicine at Mount Sinai, New York City, Internship; Developmental and regenerative biology, Liver department, Associate Professor Dr. Kirsten Sadler-Edepli  

2013            Berlin-Brandenburg Centre for Regenerative Therapies (BCRT), Internship; Immunogenicity/ immunomodulation profiles of cells and biomaterials, Dr. Martina Seifert

2012                  Roche Diagnostics GmbH, Penzberg, Internship; Therapeutic cell initiative, Dr. Markus Neubauer

2008-2011   Bachelor of Sciences in Life Science, University of Applied Sciences Berlin. Thesis: "Investigating the putative application of fragment analysis for sexing of South African bird population." Inqaba Biotechnical Industries Ltd, Pretoria, South Africa

Publications

1. Scheibner K*, Schirge S*, Burtscher I*, Büttner M, Sterr M, Yang D, Böttcher A, Ansarullah, Irmler M, Beckers J, Cernilogar FM, Schotta G, Theis FJ and Lickert H.  (2021) Epithelial cell plasticity drives endoderm formation during gastrulation. Nat Cell Biol. Jul;23(7):692-703.  doi.org/10.1038/s41556-021-00694-x

2. Salinno C, Büttner M, Cota P, Tritschler S, Tarquis-Medina M, Bastidas-Ponce A, Scheibner K, Burtscher I, Böttcher A, Theis FJ, Bakhti M, Lickert H. (2021) CD81 marks immature and dedifferentiated pancreatic β-cells. Mol Metab. Jul;49:101188. doi: 10.1016/j.molmet.2021.101188. 

3. Mahaddalkar, PU*; Scheibner, K*; Pfluger, S; Ansarullah; Sterr, M; Beckenbauer, J; Irmler, M; Beckers, J; Knöbel, S; Lickert, H (2020) Generation of pancreatic β cells from CD177+ anterior definitive endoderm. Nat. Biotechnol. 38(9):1061-1072

4. Bastidas-Ponce, A; Tritschler, S; Dony, L; Scheibner, K; Tarquis Medina, M; Salinno, C; Schirge, S; Burtscher, I; Böttcher, A; Theis, FJ; Lickert, H; Bakhti, M (2019) Comprehensive single cell mRNA profiling reveals a detailed roadmap for pancreatic endocrinogenesis. Development 146: dev173849

5. Cernilogar, FM; Hasenöder, S;Wang, Z; Scheibner, K; Burtscher, I; Sterr, M; Smialowski, P; Groh, S; Evenroed, IM; Gilfillan, GD; Lickert, H*; Schotta, G* (2019) Pre-marked chromatin and transcription factor co-binding shape the pioneering activity of Foxa2. Nucleic Acids Res. 47, 9069-9086

6. Bakhti, M*; Scheibner, K*; Tritschler, S; Bastidas-Ponce, A; Tarquis-Medina, M; Theis, FJ; Lickert  (2019) Establishment of a high-resolution 3D modeling system for studying pancreatic epithelial cell biology in vitro. Molecular Metabolism 30 16-29

7. Scheibner, K; Bakhti, M; Bastidas-Ponce, A; Lickert, H (2019) Wnt signaling: implications in endoderm development and pancreas organogenesis. Curr Opin Cell Biol. 61 48-55

8. Bastidas-Ponce, A*; Scheibner, K*; Lickert, H; Bakhti, M (2017) Cellular and molecular mechanisms coordinating pancreas development. Development 144(16) 2873-2888.