Pancreatic Development, Stem Cell Dfferentiation and Cancer

AG Prof. Dr. Kleger

 

Our laboratory aims for a better understanding of the biology, pathology, and clinical utility of pancreatic development, inherited pancreatic syndromes and pancreatic cancer using human and murine pluripotent stem cells and genetically engineered mouse models (GEM). We focus our studies on pancreas development and on common mechanisms of pluripotent stem cell biology and cancer. Our goals are to define principles of how pluripotent stem cells commit toward the mature pancreatic lineages using the progeny as a patient-specific disease model.

Thereby, we have built up resources for pancreatic disease modelling such as an iPS cell bank including a series of inherited pancreatic disease and various genetically engineered mouse strains lacking DNA damage repair genes in the context of Kras driven carcinogenesis. The latter aim to mimic certain human subtypes of pancreatic ductal adenocarcinoma (PDAC).  

Profilbild von Prof. Dr. rer. med. Alexander Kleger

Prof. Dr. rer. med. Alexander Kleger

Heisenberg Professor für Molekulare Onkologie, Oberarzt, Innere Medizin und Gastroenterologie

Alexander Kleger has been trained as an MD and graduated in 2006. He obtained a doctoral grade in biomedical science “summa cum laude” and habilitated in 2013 with his work „Stem cell differentiation and cellular reprogramming as clinically relevant model systems“ after a postdoctoral fellowship at the Institute for Molecular Medicine and Max-Planck-Research Group for Stem Cell Aging.

His laboratory implements human and mouse pluripotent stem cells and genetically engineered mouse models to study pancreatic development, inherited pancreatic syndromes and pancreatic cancer. His research received numerous awards such as the Adolf-Kußmaul Prize, the prestigious UEGW Top Abstract Award and most recently the Rising Star Award of the UEG. He is a former and current Else-Kröner Fresenius fellow.

For more details click on his curriculum vitae.

 

 

Research Groups and People

News

Jessica Merkle (M.Sc.) receives Travel Grant and Abstract Prize at the DPC congress in Halle (Saale).

 

Deutscher Pankreas Club (DPC) congress:

Markus Breunig (M. Sc.) and Dr. rer. nat. Karolin Walter receive Travel Grant/Abstract Prize.

 

United European Gastroenterology Week in Barcelona:

Dr. rer. nat. Sandra Heller and Frank Arnold (M.Sc.) receive Travel Grant/Poster Prize.

 

Alexander Kleger honored by UEG Rising Star 2018.

https://www.dgvs.de/dgvs-im-blick/dgvs-preistraeger/rising-star-2018/

Annual Meeting of the German Pancreatic Club in Ulm.

http://www.dpc-kongress.de/

M. Sc. Frank Arnold receives Abstract Prize and Dr. rer. nat. Meike Hohwieler receives Poster Prize.

Jahrestagung der Deutschen Gesellschaft für Verdauungs- und Stoffwechselkrankheiten (DGVS).

Jessica Merkle (M.Sc.) receives Otto-Porges Prize.

Markus Breunig (M.Sc.) receives Rudolf-Schindler Abstract Prize.

Frank Arnold (M.Sc.) receives Travel Grant.

 

 

UEGW

Dr. Johann Gout, Jessica Merkle (M.Sc.) and Frank Arnold (M.Sc.) receive Travel Grants at the United European Gastroenterology Week.

 

 

New publication Hohwieler et al.
“Human pluripotent stem cell-derived acinar/ductal organoids generate human pancreas upon orthotopic transplantation and allow disease modelling”
at the Cover of GUT.

Dr. med. Lukas Perkhofer receives prestigious Martin Gülzow-Award at the DGVS.

Für grundlegende und richtungsweisende Arbeiten im Bereich der klinischen Gastroenterologie vergibt die Fachgesellschaft den Martin Gülzow-Preis. 2017 geht dieser an Dr. Lukas Perkhofer aus Ulm seine Arbeit mit dem Titel „Der Verlust von ATM generiert genomische Instabilität und ermöglicht neue therapeutische Strategien des duktalen Pankreaskarzinoms“. Die Vergabe des Preises erfolgt mit freundlicher Unterstützung der MSD SHARP & DOHME GMBH.

 

Dr. rer. nat. Meike Hohwieler receives Otto-Porges Preis at 72. Jahrestagung der Deutschen Gesellschaft für Verdauungs- und Stoffwechselkrankheiten (DGVS).

 

Tailored therapies for ATM-mutated cancer, Perkhofer et al.  “ATM Deficiency Generating Genomic Instability Sensitizes Pancreatic Ductal Adenocarcinoma Cells to Therapy-Induced DNA Damage” goes online.


Kleger lab receives 3 Travel Grants 1.000 € for abstracts of Dr. rer. nat. Meike Hohwieler, Markus Breunig
and Dr. med. Lukas Perkohofer.

Sandra Heller receives the 10.000 £ Lush Prize.

http://lushprize.org/de/preistraeger-2017/

Animal-free diabetes modelling on an iPSC chip platform.

In 2015, the German federal institute for risk assessment granted animal studies with a total number of 25K mice for diabetes research. In order to substantially reduce the number of mice we are currently missing an in vitro cell system recapitulating the function of pancreatic insulin-producing islets. Therefore, we plan to establish a chip platform to culture thousands of micro-islets that can be stimulated with glucose and drug components. Finally, we will be able to analyze different secreted proteins from these treated insulin-producing islets.

For the production of human micro-islets, we will differentiate human embryonic stem cells (ESC) or human induced pluripotent stem cells (iPSC) generated from patient tissue into pancreatic hormone-producing cells according to a recently published differentiation protocol. Then, we will optimize the formation of micro-islets with agarose micro-well arrays by testing the number of required cells in the array, the duration of the formation process, and viability of the micro-islets in the print chip platform.

Finally, to investigate insulin and glucagon secretion of human micro-islets under variable conditions we plan to apply the chip technology. This will help to replace animal testing in diabetes research and facilitate a faster and more physiological and personalized analysis.

 

Markus Breunig receives Poster Prize when attending the Stem Cell Society Singapore Meeting.

 

Liebau and Kleger lab dissect the process of reprogramming toward induced pluripotency.

www.ncbi.nlm.nih.gov/pubmed/29185460

Dr. rer. nat. Meike Hohwieler receives best poster ward at the 4th Annual Conference of the GSCN in Hannover.

 

 

Publications

  1. Perkhofer L, Gout J, Roger E, Kude de Alemeida F, Baptista Simoes C, Wiesmüller L, Seufferlein T, Kleger A (2021). DNA damage repair as a target in pancreatic cancer: state-of-the-art and future perspectives. Gut, 70(3):606-617.

  2. Wiedenmann, S., Breunig, M., Merkle, J., von Törne, C., Hauck, S., Georgiev T., Moussus, M., Hohwieler, M., Kleger, A., Meier, M.:  Charting ductal differentiation in a pancreas-on-chip model with single-cell resolution, Nature Biomedical Engineering. First submission 08-2020

  3. Breunig, M., Merkle, J., Wagner, M., Melzer, M. K., Barth T.F.E., (...) Kuster, B., Seufferlein, T., Rad, R., Meier, M., Hohwieler, M., Kleger, A.: Modelling Plasticity and Dysplasia of Pancreatic Ductal Organoids Derived from Human Pluripotent Stem Cells, Cell Stem Cell, first submission 05-2020, proceed with publication 02-2021

  4. Müller, Janis A., Rüdiger Groß, Carina Conzelmann, Jana Krüger, Uta Merle, Johannes Steinhart, Tatjana Weil et al. "SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas." Nature Metabolism (2021): 1-17.

  5. Melzer, M.K.; Arnold, F.; Stifter, K.; Zengerling, F.; Azoitei, N.; Seufferlein, T.; Bolenz, C.; Kleger, A. An Immunological Glance on Pancreatic Ductal Adenocarcinoma. Int. J. Mol. Sci. 2020, 21, 3345. doi.org/10.3390/ijms21093345

  6. Arnold F, Gout J, Wiese H, Weissinger S, Roger E, Perkhofer L, Walter K, Scheible J, Prelli-Bozzo C, Lechel A, Ettrich TJ, Azoitei N, Hao L, Fuerstberger A, Kaminska EK, Sparrer KMJ, Rasche V, Wiese S, Kestler HA, Möller P, Seufferlein T, Frappart PO, Kleger A. RINT1 regulates SUMOylation and the DNA damage response to preserve cellular homeostasis in pancreatic cancer. Cancer Res. 2021 Feb 2:canres.2633.2020. doi: 10.1158/0008-5472.CAN-20-2633. Epub ahead of print. PMID: 33531371

  7. Stifter K, Krieger J, Ruths L, Gout J, Mulaw M, Lechel A, Kleger A, Seufferlein T, Wagner M, Schirmbeck R. IFN-γ treatment protocol for MHC-I lo/PD-L1 + pancreatic tumor cells selectively restores their TAP-mediated presentation competence and CD8 T-cell priming potential J Immunother Cancer. 2020 Aug;8(2):e000692. doi: 10.1136/jitc-2020-000692.

  8. Schulte LA, Arnold F, Siegel F, Backhus J, Beyer G, Weiss FU, Perkhofer L, Beutel A, Seufferlein T, Müller M, Kleger A. Serum IgG4 levels outperform IgG4/IgG RNA ratio in differential diagnosis of IgG4-related disease. JHEP Rep. 2020 Jun 3;2(4):100135. doi: 10.1016/j.jhepr.2020.100135. PMID: 32743490; PMCID: PMC7385040

  9. Frappart PO, Walter K, Gout J, Beutel AK, Morawe M, Arnold F, Breunig M, Barth TF, Marienfeld R, Schulte L, Ettrich T, Hackert T, Svinarenko M, Rösler R, Wiese S, Wiese H, Perkhofer L, Müller M, Lechel A, Sainz B Jr, Hermann PC, Seufferlein T, Kleger A. Pancreatic cancer-derived organoids - a disease modeling tool to predict drug response. United European Gastroenterol J. 2020 Jun;8(5):594-606. doi: 10.1177/2050640620905183. Epub 2020 Feb 19. Erratum in: United European Gastroenterol J. 2020 Oct;8(8):987. PMID: 32213029; PMCID: PMC7268941.

  10. Krüger, J., Groß, R., Conzelmann, C., Müller, J. A., Koepke, L., Sparrer, K. M., ... & Stenger, S. (2020). Drug inhibition of SARS-CoV-2 replication in human pluripotent stem cell-derived intestinal organoids. Cellular and Molecular Gastroenterology and Hepatology.

  11. Roger, E., Gout, J., Arnold, F., Beutel, A. K., Müller, M., Abaei, A., ... & Kleger, A. (2020). Maintenance Therapy for ATM-Deficient Pancreatic Cancer by Multiple DNA Damage Response Interferences after Platinum-Based Chemotherapy. Cells, 9(9), 2110.

  12. Conzelmann, C., Müller, J. A., Perkhofer, L., Sparrer, K. M., Zelikin, A. N., Münch, J., & Kleger, A. (2020). Inhaled and systemic heparin as a repurposed direct antiviral drug for prevention and treatment of COVID-19. Clinical Medicine, 20(6), e218.PERKHOFER, Lukas, et al. DNA damage repair as a target in pancreatic cancer: state-of-the-art and future perspectives. Gut, 2020.

  13. Michel, D., Danzer, K. M., Groß, R., Conzelmann, C., Müller, J. A., Freischmidt, A., ... & Stamminger, T. (2020). Rapid, convenient and efficient kit-independent detection of SARS-CoV-2 RNA. Journal of Virological Methods, 286, 113965.

  14. Gout, J., Perkhofer, L., Morawe, M., Arnold, F., Ihle, M., Biber, S., ... & Hahn, S. A. (2020). Synergistic targeting and resistance to PARP inhibition in DNA damage repair-deficient pancreatic cancer. Gut.

  15. Huang, L., Bockorny, B., Paul, I., Akshinthala, D., Frappart, P. O., Gandarilla, O., ... & Pandell, N. (2020). PDX-derived organoids model in vivo drug response and secrete biomarkers. JCI insight, 5(21).

  16. Klingenstein, S., Klingenstein, M., Kleger, A., & Liebau, S. (2020). From hair to iPSCs—A guide on how to reprogram keratinocytes and why. Current Protocols in Stem Cell Biology, 55(1), e121.

  17. Frappart P, Walter K, Gout J, Beutel A, Morawe M, Frank A, Breunig M, Barh T, Marienfeld R, Schulte L, Ettrich T, Hackert T, Svinarenko M, Rösler R, Wiese S, Wiese H, Perkhofer L, Müller M, Lechel A, Sainz B, Herrmann P, Seufferlein T, Kleger A. Pancreatic cancer-derived organoids – a potential tool to predict drug response. UEG Journal, 2020,in press

  18. Meike Hohwieler, Martin Müller, Pierre-Olivier Frappart, Sandra Heller. (2019). Pancreatic progenitors and organoids as a prerequisite to model pancreatic diseases and cancer. Stem Cells International, Review, 2019:9301382.

  19. Armacki, M., Trugenberger, A.K., Ellwanger, A.K., Eiseler, T., Schwerdt, C., Bettac, L., Langgartner, D., Azoitei, N., Halbgebauer, R., Groß, R. and Barth, T. (2018). Thirty-eight-negative kinase 1 mediates trauma-induced intestinal injury and multi-organ failure. The Journal of clinical investigation, 128(11).

  20. Hohwieler M, Illing A, Hermann PC, Mayer T, Stockmann M, Perkhofer L, Eiseler T, Antony JS, Müller M, Renz S, Kuo CC, Lin Q, Sendler M, Breunig M, Kleiderman SM, Lechel A, Zenker M, Leichsenring M, Rosendahl J, Zenke M, Sainz B Jr, Mayerle J, Costa IG, Seufferlein T, Kormann M, Wagner M, Liebau S, Kleger A. (2016). Human pluripotent stem cell-derived acinar/ductal organoids generate human pancreas upon orthotopic transplantation and allow disease modelling. Gut, 312423.

  21. Perkhofer L, Walter K, Costa IG, Carrasco MC, Eiseler T, Hafner S, Genze F, Zenke M, Bergmann W, Illing A, Hohwieler M, Köhntop R, Lin Q, HolzHolzmann KH, Seufferlein T, Wagner M, Liebau S, Hermann PC, Kleger A, Müller M. (2016). Tbx3 fosters pancreatic cancer growth by increased angiogenesis and activin/nodaldependent induction of stemness. Stem Cell Res 17(2), 367-378

  22. Berger A, Schwerdel D, Costa IG, Hackert T, Strobel O, Lam S, Barth T, Schröppel B, Meining A, Büchler MW, Zenke M, Hermann PC, Seufferlein T, Kleger A. (2016). Circulating cell-free DNA is a reliable tool to detect hot spot mutations in intraductal papillary mucinous neoplasms of the pancreas. Gastroenterology 151(2), 267-70

  23. Ernst K, Schmid J, Beck M, Hägele M, Hohwieler M, Hauff P, Ückert AK, Anastasia A, Fauler M, Jank T, Aktories K, Popoff MR, Schiene-Fischer C, Kleger A, Müller M, Frick M, Barth H. (2016). "Miniguts" from plucked human hair meet Crohn's disease. Z. Gastroenterol. 54, 748-759

  24. Hohwieler M, Perkhofer L, Liebau S, Seufferlein T, Müller M, Illing A, Kleger A. (2017). Stem cell-derived organoids to model gastrointestinal facets of cystic fibrosis. United European Gastroenterol. J. 5, 609-624, Review article

  25. Ernst K, Schmid J, Beck M, Hägele M, Hohwieler M, Hauff P, Ückert AK, Anastasia A, Fauler M, Jank T, Aktories K, Popoff MR, Schiene-Fischer C, Kleger A, Müller M, Frick M, Barth H. (2017). Hsp70 facilitates trans-membrane transport of bacterial ADP-ribosylating toxins into the cytosol of mammalian cells. Sci. Rep. 7, 2724

  26. Raab S, Klingenstein M, Möller A, Illing A, Tosic J, Breunig M, Kuales G, Linta L, Seufferlein T, Arnold SJ, Kleger A, Liebau S. (2017). Reprogramming to pluripotency does not require transition through a primitive streak-like state. Scientific Reports 7(1), 16543

  27. Perkhofer L, Schmitt A, Romero Carrasco MC, Ihle M, Hampp S, Ruess DA, Hessmann E, Russell R, Lechel A, Azoitei N, Lin Q, Liebau S, Hohwieler M, Bohnenberger H, Lesina M, Algül H, Gieldon L, Schröck E, Gaedcke J, Wagner M, Wiesmüller L, Sipos B, Seufferlein T, Reinhardt HC, Frappart PO, Kleger A. (2017). ATM Deficiency Generating Genomic Instability Sensitizes Pancreatic Ductal Adenocarcinoma Cells to Therapy-Induced DNA Damage. Cancer Research 77(20), 5576-5590.

  28. Perkhofer L, Walter K, Costa IG, Carrasco MC, Eiseler T, Hafner S, Genze F, Zenke M, Bergmann W, Illing A, Hohwieler M, Köhntop R, Lin Q, Holzmann KH, Seufferlein T, Wagner M, Liebau S, Hermann PC #, Kleger A #, Müller M. Tbx3 fosters pancreatic cancer growth by increased angiogenesis and activin/nodal-dependent induction of stemness. Stem Cell Res. 2016 Sep;17(2):367-378. doi: 10.1016/j.scr.2016.08.007

  29. Rasch S, Phillip V, Reichel S, Rau B, Zapf C, Rosendahl J, Halm U, Zachäus M, Müller M, Kleger A, Neesse A, Hampe J, Ellrichmann M, Rückert F, Strauß P, Arlt A, Ellenrieder V, Gress TM, Hartwig W, Klar E, Mössner J, Post S, Schmid RM, Seufferlein T, Siech M, Werner J, Will U, Algül H. (2016) Open Surgical versus Minimal Invasive Necrosectomy of the Pancreas-A Retrospective Multicenter Analysis of the German Pancreatitis Study Group.PLoS One. 2016 Sep 26;11(9):e0163651. doi: 10.1371/journal.pone.0163651. eCollection 2016.

  30. Berger A, Schwerdel D, Costa IG, Hackert T, Strobel O, Lam S, Barth T, Schröppel B, Meining A, Büchler MW, Zenke M, Hermann PC, Seufferlein T #, Kleger A #. # corresponding authors.(2016). Circulating cell-free DNA is a reliable tool to detect hot spot mutations in intraductal papillary mucinous neoplasms of the pancreas. Gastroenterology, 2016, Aug;151(2):267-70.

  31. Sroka R, Van Lint J, Katz SF, Schneider MR, Kleger A, Paschke S, Seufferlein T, Eiseler T (2016). Cortactin is a scaffolding platform for the E-cadherin adhesion complex and is regulated by protein kinase D1 phosphorylation. J Cell Sci. 2016 Jun 15;129(12):2416-29. doi: 10.1242/jcs.184721. Epub 2016 May 13.

  32. Hohwieler M1, Renz S, Liebau S, Lin Q, Lechel A, Klaus J, Perkhofer L, Zenke M, Seufferlein T, Illing A, Müller M, Kleger A.„Miniguts" from plucked human hair meet Crohn´s disease. Gastroenterol, 2016, 2016 Aug;54(8):748-59.

  33. Russell R, Ilg M, Lin Q, Wu G, Linta L, Hohwieler M, Lechel A, Bergmann W, Kumar PP, Klingenstein M, Sakk O, Raab S, Moon A, Zenke M, Seufferlein T, Schöler H, Illing A, Liebau S, Kleger A. A dynamic role of Tbx3 in the pluripotency circuitry. Stem Cell Reports, 2015 Dec 8;5(6):1155-70.

  34. Klingenstein M, Raab S, Achberger K, Kleger A #, Liebau S #, Linta L #. # corresponding authors. TBX3 knockdown decreases reprogramming efficiency of human cells. Stem Cells Int., 2016;2016:6759343.

  35. Müller M, Schröer S, Azoitei N, Eiseler T, Bergmann W, Köhntop R, Lin L, Zenke M, Genze F, Weidgang C, Seufferlein T, Liebau S #, Kleger A #. #corresponding authors. A time frame permissive for Protein Kinase D2 activity to direct angiogenesis in mouse embryonic stem cells. Scientific Reports, 2015 Jul 7;5:11742. doi: 10.1038/srep11742.

  36. Martin Müller, Thomas Seufferlein, Martin Wagner, Alexander Kleger. Self-expandable metal stents for persisting esophageal variceal bleeding after band ligation or injection-therapy: A retrospective study.PLoS One, PLoS One. 2015 Jun 22;10(6):e0126525.

  37. Weidgang CE *, Russell R *, Tata PR *, Kühl SJ, Illing A, Müller M, Lin Q, Brunner C, Boeckers TM, Bauer B, Kartikasari AER, Guo Y, Radenz M, Bernemann C, Weiß M, Seufferlein S, Zenke M, Iacovino M, Kyba M, Schöler HR, Kühl M, Liebau S #, and Kleger A #. * equal contribution. # corresponding authors. TBX3 Directs Cell-Fate Decision toward Mesendoderm.Stem Cell Reports, ISSCR and Cell Press, 2013 Aug 29;1(3):248-65.

  38. Schmid SJ *, Glatzel MC*, Welke C, Kornmann M, Kleger A, Barth TFE, Fulda S, Lennerz JK, and Möller. * equal contribution. Absence of FLICE-Inhibitory Protein Is a Novel Independent Prognostic Marker for Very Short Survival in Pancreatic Ductal Adenocarcinoma. Pancreas, 2013, Oct;42(7):1114-9.

  39. Illing A *, Stockmann M *, Telugu NS, Linta L, Russell R, Müller M, Seufferlein T, Liebau S #, Kleger A #. * equal contribution. # corresponding authors. Definitive Endoderm Formation from Plucked Human Hair-Derived Induced Pluripotent Stem Cells and SK Channel Regulation. Stem Cells Int, 2013;2013:360573.

  40. Linta L, Stockmann M, Lin Q, Lechel A, Proepper Ch, Boeckers TM, Kleger A #, Liebau L #. # corresponding authors. Microarray-Based Comparisons of Ion Channel Expression Patterns: Human Keratinocytes to Reprogrammed hiPSCs to Differentiated Neuronal and Cardiac Progeny. Stem Cells Int, 2013, 2013:784629.

  41. Linta L, Boeckers TM, Kleger A #, Liebau S #. # corresponding authors. Calcium activated potassium channel expression during human iPS cell-derived neurogenesis. Ann Anat. 2013 Mar 28.

  42. Kleger A * #, Mahaddalkar P *, Katz SF, Lechel A, Ju JY, Loya K, Lin Q, Hartmann D, Liebau S, Kraus J, Cantz T, Kestler HA, Zaehres H, Schöler H, Rudolph KL #. * equal contribution. # corresponding authors. Increased Reprogramming Capacity of Mouse Liver Progenitor Cells, Compared With Differentiated Liver Cells, Requires the BAF Complex. Gastroenterology. 2012 Apr;142(4):907-17.

  43. Stockmann M, Linta L, Föhr KJ, Boeckers A, Ludolph AC, Kuh GF, Udvardi PT, Proepper C, Storch A, Kleger A, Liebau S, Boeckers TM. Developmental and functional nature of human iPSC derived motoneurons.  Stem Cell Reviews and Reports, 2011 Nov 3.

  44. Müller M *, Stockmann M *, Malan D, Wolheim A, Tischendorf M, Linta L, Katz SF, Lin Q, Latz S, Brunner C, Wobus AM, Zenke M, Wartenberg M, Boeckers TB, von Wichert G, Fleischmann BF, Liebau S #, Kleger A #. Ca2+-activated K+-Channels - New Tools to induce Cardiac Commitment from Pluripotent Stem Cells in Mice and Men. Stem Cell Reviews and Reports, 2012 Sep;8(3):720-40.

  45.  Liebau S, Tischendorf M, Ansorge D, Linta L, Stockmann M, Weidgang C, Iacovino M, Boeckers T, Kyba M, Kleger A. An inducible expression system of the calcium activated potassium channel 4 to study the differential impact on embryonic stem cells. Stem Cells Int. 2011;2011:456815.

  46. Azoitei N *, Kleger A *, Schoo N, Thal D, Brunner C, Pusapati GV, Filatova A, Genze F, Möller P, Acker T, Kuefer R, Van Lint J, Baust H, Adler G, Seufferlein T. *equal contribution. Protein kinase D2 is a novel regulator of glioblastoma growth and tumor Formation. Neuro Oncol. 2011 Jul;13(7):710-24.

  47.  Linta L, Stockmann M, Böckers A, Böckers TM, Kleger A # and Liebau S #.  # corresponding authors. Rat embryonic fibroblasts improve reprogramming of human keratinocytes into induced pluripotent stem cells. Stem Cells Dev. 2012 Apr 10;21(6):965-76.

  48. Hartmann D, Srivastava U, Thaler M, Kleinhans KN, N'kontchou G, Scheffold A, Bauer K, Kratzer RF, Kloos N, Katz SF, Song Z, Begus-Nahrmann Y, Kleger A, von Figura G, Strnad P, Lechel A, Günes C, Potthoff A, Deterding K, Wedemeyer H, Ju Z, Song G, Xiao F, Gillen S, Schrezenmeier H, Mertens T, Ziol M, Friess H, Jarek M, Manns MP, Beaugrand M, Rudolph KL. Telomerase gene mutations are associated with cirrhosis Formation. Hepatology. 2011 May;53(5):1608-17.

  49.  Liebau S, Steinestel J, Linta L, Kleger A, Storch A, Schoen M, Steinestel K, Proepper C, Bockmann J, Schmeisser MJ, Boeckers TM. An SK3 Channel/nWASP/Abi-1 complex is involved in early neurogenesis. PLoS One. 2011 Mar;6(3):e14599.

  50. Figura G, Wagner M, Nalapareddy K, Hartmann D, Kleger A, Adler G, Rudolph KL. Regeneration of the exocrine pancreas is delayed in telomere-dysfunctional mice. PLoS One. 2011 Feb 22;6(2):e17122.

  51. Kleger A *, Loebnitz C *, Pusapati GV, Müller M, Tümpel S, Illing A, Hartmann D, Brunner C, Liebau S, Adler G, Seufferlein T. * equal contribution.  Protein kinase D2 is an essential regulator of murine myoblast Differentiation. PLoS One. 2011 Jan 27;6(1):e14599.

  52.  Kleger A, Seufferlein T, Malan D, Tischendorf M, Storch A, Wolheim A, Protze S, Porzner M, Proepper C, Brunner C, Katz SF, Pusapati GV, Bullinger L, Köhntopp R, Giehl K, Spyrantis A, Wittekindt O, Lin Q, Zenke M, Fleischmann BK, Wartenberg M, Wobus AM, Boeckers TM and Liebau S. Modulation of calcium-activated potassium channels induces cardiogenesis of pluripotent stem cells and enrichment of pacemaker-like cells. Circulation. 2010 Nov 2;122(18):1823-36.

  53.  Kleger A, Busch T, Liebau S, Prelle K, Paschke S, Beil M, Rolletschek A, Wobus AM, Wolf E, Adler G, Seufferlein T. The bioactive lipid sphingosylphosphorylcholine induces differentiation of mouse embryonic stem cells and human promyelocytic leukaemia cells. Cell Signal. 2007 Feb;19(2):367-77.

  54. Herrmann A, Maisel M, Liebau S, Gerlach M, Kleger A, Schwarz J, Kim KS, Antoniadis G, Lerche H, Storch A. Mesodermal cell types induce neurogenesis from adult human hippocampal progenitor cells. Neurochem. 2006; 98 (2): 629-40.

  55. Schulte-Kemna L, Kornmann M, Kleger A. An exceptional cause of epigastric pain. Gastroenterology, 2016 Jun;150(7):e1-e2.

  56. van Erp RJ, Schröppel B, Barth TF, Seufferlein T, Schmidt SA, Meining A, Kleger A. A rare cause of upper GI bleeding and wasting disease. GUT. 2016 May;65(5):787, 881.

  57. Kleger A, Schnell J, Essig A, Wagner M, Bommer M, Seufferlein T, Härter G. Case report: Fecal transplantation therapy in refractory clostridium difficile colitis. Dtsch Arztebl Int. 2013 Feb;110(7):108.

  58.  Kleger A #, Bommer M, Kunze M, Klaus J, Leithaeuser F, Wegener M, Adler G, Dikopoulos N. # corresponding author. First reported case of disease: Peliosis hepatis as cardinal symptom of Hodgkin's lymphoma. Oncologist. 2009 Nov;14(11):1088-94.

 

 

 

 

Join our lab

The Kleger lab continuously offers MD positions for performing full-time research.
We usually apply for fellowships in organised programmes such as
http://www.uni-ulm.de/einrichtungen/mm/phdprogramme/expmedizin/ 

In case you are interested please send your application documents to
alexander.kleger@uni-ulm.de .

The Kleger lab continuously offers Master and Bachelor positions.
In case you are interested please send your application documents to
alexander.kleger@uni-ulm.de .

There are currently no in house funded positions available.
In case you are supported by a fellowship feel free to send your CV and full application documents to
alexander.kleger@uni-ulm.de .

 

 

Funding

 

 

Gallery

 

 

Good Old Friends

  • Dr. Ronan Russell
  • Dr. Anett Illing
  • Wendy Bergmann
  • Markus Ilg
  • Stefanie Fischer
  • Clair Weidgang
  • Christiane Loebnitz
  • Michael Tischendorf