Download PD Dr. Tobias CANTZ

CURRICULUM VITAE
Tobias Cantz, MD
REBIRTH cluster of Excellence
Hannover Medical School and Max Planck Institut Münster
Translational Hepatology and Stem Cell Biology
Carl-Neuberg-Str. 1
30625 Hanover, Germany
www.rebirth-hannover.de/cantz
e-mail: [email protected]
Academic Curriculum:
1993 - 2000
Studies of Medicine, Ruprecht Karls University, Heidelberg, Germany
1997 - 2000
Doctorate at German Cancer Research Center (DKFZ) Heidelberg, Germany. Dept.
of Tumorbiochemistry (Prof. D. Keppler)
2000 - 2004
Physician and staff scientist Dept. of Gastroenterology, Hepatology and
Endocrinology, Medical School Hannover, Germany (Prof. M. Manns)
2004 - 2008
Staff scientist, Max Planck Institute for Molecular Biomedicine, Muenster,
Germany (Hans R. Schöler)
2008 - present
Head of the Research Group ‘Translational Hepatology and Stem Cell Biology’ in
the Cluster of Excellence REBIRTH, Hannover Medical School, Germany
Scientific Awards:
2007
Coordinator of www.zellux.net (web-based teaching material for high school
pupils on ethics and therapeutic perspectives of human embryonic stem cells)
2011
Pro Scientia Prize of the Eckhart-Buddecke-Foundation
2013
Founding Member of the German Stem Cell network (www.gscn.org)
Research Interests:
Stem cell biology in hepatic differentiation and regeneration, generation of induced pluripotent stem
cells (iPS cells), molecular mechanisms underlying epigenetic reprogramming / trans-programming,
stem cell-based liver disease models, ethical aspects of embryonic stem cell and iPS cell research.
Selected Publications:
Eggenschwiler R, Loya K, Wu G, Sharma AD, Sgodda M, Zychlinski D, Herr C, Steinemann D, Teckman
J, Bals R, Ott M, Schambach A, Schöler HR, Cantz T (2013). Sustained knockdown of a diseasecausing gene in patient specific induced pluripotent stem cells using lentiviral vector based gene
therapy. Stem Cells Translat Med. 2(9):641-54.
Pfaff N & Cantz T (2013). From Skin to Blood: A New Member Joins the iClub. Cell Stem Cell.
13(2):131-3.
Sgodda M, Möbus S, Hoepfner J, Sharma AD, Schambach A, Greber B, Ott M, Cantz T (2013).
Improved Hepatic Differentiation Strategies for Human Induced Pluripotent Stem Cells. Curr Mol
Medicine, 13(5):842-55.
Pfaff N, Fiedler J, Holzmann A, Schambach A, Moritz T, Cantz T*, Thum T* (2011). MiRNA screening
reveals a new miRNA family stimulating iPS cell generation via regulation of Meox2.
EMBOreports 12(11):1153-59 (*corresponding authors)
Wu G, Liu N, Rittelmeyer I, Sharma AD, Sgodda M, Zaehres H, Bleidissel M, Greber B, Gentile L, Han
DW, Rudolph C, Steinemann D, Schambach A, Ott M, Schöler HR, Cantz T (2011). Generation of
Healthy Mice from Gene-Corrected Disease-Specific Induced Pluripotent Stem Cells. PLoS Biol
9(7): e1001099
2
Abstract:
Direct reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) is a promising
approach for the derivation of disease-specific iPSCs. In the clinical setting, patient-specific iPSCs
must undergo repair prior to autologous cell transplantation if the underlying condition was caused
by a genetic disorder and long-term functional capabilities of the gene-corrected cells needs to be
ensured. Aiming at robust reprogramming protocols we investigated the effects of all 16
reprogramming factor stoichiometries and evaluated a versatile polycistronic reprogramming vector,
expressing all four factors (Oct4, Sox2, Klf4, and c-Myc). Furthermore, we identifed several
microRNAs, whose modulation improved the efficacy of iPS cell generation.
Moreover, we evaluated a cytokine and small molecule based protocol for direct differentiation of
human embryonic stem cells (hESC) and hiPS cells into hepatic cells that could be visualized and
selected by a lentiviral albumin-GFP/Neo construct. Functional characterization of these cells allowed
the recapitulation of the disease phenotype for further studies of underlying molecular mechanisms
of the respective disease. Aiming at a sustained knock-down of a disease causing gene in iPSCs and
their differentiated derivatives, we investigated a novel approach for the expression of a therapeutic
shRNA in α-1-antitrypsin deficiency (A1AT)-specific iPSC using third generation lentiviral vectors. With
this novel strategy, we were able to achieve a significant reduction in the expression of the mutated
PiZ-A1At variant in transduced and differentiated disease specific iPSC from a murine model and from
one individual suffering from severe α-1-antitrypsin deficiency-associated liver disease.
With respect to stem cell-based therapies, often postulated hypotheses suggested that more
proliferative fetal or stem cell-derived hepatic cells perform better as hepatic cell transplants than
adult hepatocytes and, therefore, should be considered as preferential cell source. In a xenograftaccepting mouse strain, which serves as competitive liver repopulation model, we could not confirm
such hypotheses, but our results suggested that the maturity of transplanted cells has a major effect
of engraftment and repopulation efficiencies. Therefore, we aim at further improvements in the
hepatic differentiation protocols of human pluripotent stem cells that eventually yield in
transplantable cells exhibiting long-term repopulation capabilities in xeno-graft accepting animals.