Enhanced and Synthetic Cells for Regeneration

Objectives

Our major aim is the generation of enhanced and synthetic cells for regeneration and more specifically hematopoietic cells with improved capabilities. This will include the genetic modification of hematopoietic stem cells (HSCs), hematopoietic progenitor cells as well as differentiated myeloid cells, such as monocytes/macrophages and granulocytes. Long term aims of this work are the generation of

  • HSCs and hematopoietic progenitor cells with improved engraftment and reconstitution potential and defined expression windows, and
  • generation of genetically modified granulocytes and monocytes/macrophages for the treatment of selected diseases.

Research Focus

In the first part which will focus on the expression of genes that will enhance the engraftment and repopulation ability of HSCs, we will in particular analyze and utilize the functions of genes that we discovered in our extensive studies applying insertional mutagenesis approaches. Genes successful in these studies also will be applied to hematopoietic ex vivo differentiation of pluripotent stem cells, incl. induced pluripotent stem cells (iPSC). These studies will be guided by our previous experience with HoxB4 and other transcription factors found to promote HSC differentiation and fitness. Here, in addition to genes encoding for transcription factors, signalling molecules and factors required for survival and genomic integrity also specific miRNAs and lnRNAs will be screened for their function in early hematopoietic as well as myeloid (and lymphoid) differentiation. As a second part, we will modify myeloid cells and other immune cells, in particular monocytes/macrophages and granulocytes; to

  • enhance site specific homing to specific tissues (e.g. liver vs. lung vs skin etc), or
  • direct these cells to specific disease sites (inflammation, tumor, macro- and microvascular diseases), and/or
  • to deliver therapeutic molecules (cytokines, toxins etc), also influencing and shaping the local microenvironment.
  • In this context, inducible and reversible expression of the therapeutic molecules will be investigated utilizing vector constructs already optimized for this purpose in our lab.
  • Safer vector and improved gene editing technologies (incl. CRISPR-Cas9) will be employed to delivery and expression these therapeutic transgene modules.

Collaborations (selection)

  • U. Modlich (Frankfurt & Paul Ehrlich Institute Langen): Analysis of stem cell function in mpl-deficiency models; insertional mutagenesis studies in murine and human HSCs; iPSC differentiation into platelets
  • T. Thum (REBIRTH-Unit miRNA in Myocardial Regeneration), H. Klusmann (REBIRTH & MHH; now University of Halle), Andreas Krueger (REBIRTH: now University of Frankfurt): Role of miRNAs and lncRNAs in early hematopoietic development as well as differentiation and regeneration
  • T. Cantz, REBIRTH-Unit Translational Hepatology and Stem Cell Biology, A. Sharma, REBIRTH-Unit miRNA in Liver Regeneration & R. Zweigerdt, REBIRTH-Unit Mass Production of Pluripotent Stem Cells and Derivates: Use of UCOE-elements to improve transgene expression in PSC-derived progeny; transprogramming of functional hepatocytes and disease modeling in iPSC and derived model systems
  • R. Stripecke, REBIRTH-Unit Regenerative Immune Therapy: Safety assessment of lentiviral vectors designed for human gene therapy; improved generation inducible dendritic cells
  • T. Cathomen, Freiburg: Use of ZF- and TALE-nucleases for iPSC-based gene therapy approaches 
  • H. Geiger, Ulm & M. Milsom Heidelberg: Retroviral insertional mutagenesis to discover genes conferring radioprotection and/or compensating the Fanconi anemia phenotype; HSC biology and HSC fitness enhancing genes
  • J. Bueren, Madrid & S. Cowan, Oxford: Generation of hematopoietic stem and differentiated cells from pluripotent cells
  • M. Ott (REBIRTH): Gene therapy and transcription factor mediated transdifferentiation into pancreatic beta cells
  • Julia Skokowa  & Karl Welte (REBIRTH, now University of Tübingen): Mechanisms underlying congenital neutropenia, development of iPSC-based model systems for neutropenias and novel modes of therapy
  • Katharina Sewald, Armin Braun (REBIRTH): Preclinical safety and toxicology of gene therapy, iPSC-derived hematopoiesis in teratoma models
  • Kai Wollert (REBIRTH): Inducible, conditional transgenic systems to overexpress protective and regenerative genes in myocardial infarct areas, e.g. MYDGF
  • Emmanuelle Charpentier (HZI, now MPI Berlin): Generation of novel CRISPR-Cas9 tools for gene editing and fitness-enhanced HSCs

Grants, awards (selection)

  • Genetically corrected iPSC derived macrophages (i-MAC) for innovative gene therapy strategies”, Research Alliance, PI Subproject 2. Axel Schambach (BMBF 01EK1602A) 3/2017-2/2020
  • CRACK-IT award, Axel Schambach, Michael Rothe, Frank Staal, Adrian Thrasher (100,000 GBP) for development of an improved biosafety assay to measure genotoxicity of gene therapy vectors
  • Excellence in Research Award, REBIRTH
  • German-Chinese Junior Research Group, Axel Schambach, Duanqing Pei: „Modern Applications in Biotechnology“, funded by DAAD & BMBF
  • HiLF career awards for several group members
  • Initiative "ReBIRTH goes back to school ": scientific talks for students. Persued in close cooperation with schools of lower saxony such as Gymnasium Burgdorf, Gymnasium Clausthal-Zellerfeld and IGS Albert-Einstein Schule Laatzen. Initiated by Nico Lachmann & Mania Ackermann

Publications

2013 - ongoing

2016

Stahlhut M, Schambach A, Kustikova OS. Transduction of Murine Hematopoietic Stem Cells with Tetracycline-regulated Lentiviral Vectors. Methods in molecular biology. 2016;1448:65-76.

Stahlhut M, Ha TC, Morgan M, Schambach A, Kustikova OS. Comparison of tetracycline-regulated promoters in lentiviral-based vectors in murine transplantation studies. Curr Gene Ther. 2016.

Song G, Pacher M, Balakrishnan A, Yuan Q, Tsay HC, Yang D, Reetz J, Brandes S, Dai Z, Putzer BM, Arauzo-Bravo MJ, Steinemann D, Luedde T, Schwabe RF, Manns MP, Scholer HR, Schambach A, Cantz T, Ott M, Sharma AD. Direct Reprogramming of Hepatic Myofibroblasts into Hepatocytes In Vivo Attenuates Liver Fibrosis. Cell stem cell. 2016;18(6):797-808.

Skuljec J, Cabanski M, Surdziel E, Lachmann N, Brennig S, Pul R, Jirmo AC, Habener A, Visic J, Daluge K, Hennig C, Moritz T, Happle C, Hansen G. Monocyte/macrophage lineage commitment and distribution are affected by the lack of regulatory T cells in scurfy mice. Eur J Immunol. 2016;46(7):1656-68.

Selich A, Daudert J, Hass R, Philipp F, von Kaisenberg C, Paul G, Cornils K, Fehse B, Rittinghausen S, Schambach A, Rothe M. Massive Clonal Selection and Transiently Contributing Clones During Expansion of Mesenchymal Stem Cell Cultures Revealed by Lentiviral RGB-Barcode Technology. Stem cells translational medicine. 2016;5(5):591-601.

Schott JW, Morgan M, Galla M, Schambach A. Viral and Synthetic RNA Vector Technologies and Applications. Molecular therapy : the journal of the American Society of Gene Therapy. 2016;24(9):1513-27.

Papapetrou EP, Schambach A. Gene Insertion Into Genomic Safe Harbors for Human Gene Therapy. Molecular therapy : the journal of the American Society of Gene Therapy. 2016;24(4):678-84.

Mucci A, Kunkiel J, Suzuki T, Brennig S, Glage S, Kuhnel MP, Ackermann M, Happle C, Kuhn A, Schambach A, Trapnell BC, Hansen G, Moritz T, Lachmann N. Murine iPSC-Derived Macrophages as a Tool for Disease Modeling of Hereditary Pulmonary Alveolar Proteinosis due to Csf2rb Deficiency. Stem cell reports. 2016;7(2):292-305.

Manukjan G, Ripperger T, Venturini L, Stadler M, Gohring G, Schambach A, Schlegelberger B, Steinemann D. GABP is necessary for stem/progenitor cell maintenance and myeloid differentiation in human hematopoiesis and chronic myeloid leukemia. Stem cell research. 2016;16(3):677-81.

Maetzig T, Schambach A. Development of Inducible Molecular Switches Based on All-in-One Lentiviral Vectors Equipped with Drug Controlled FLP Recombinase. Methods in molecular biology. 2016;1448:23-39.

Karpinski J, Hauber I, Chemnitz J, Schafer C, Paszkowski-Rogacz M, Chakraborty D, Beschorner N, Hofmann-Sieber H, Lange UC, Grundhoff A, Hackmann K, Schrock E, Abi-Ghanem J, Pisabarro MT, Surendranath V, Schambach A, Lindner C, van Lunzen J, Hauber J, Buchholz F. Directed evolution of a recombinase that excises the provirus of most HIV-1 primary isolates with high specificity. Nat Biotechnol. 2016;34(4):401-9.

Eggenschwiler R, Moslem M, Fraguas MS, Galla M, Papp O, Naujock M, Fonfara I, Gensch I, Wahner A, Beh-Pajooh A, Mussolino C, Tauscher M, Steinemann D, Wegner F, Petri S, Schambach A, Charpentier E, Cathomen T, Cantz T. Improved bi-allelic modification of a transcriptionally silent locus in patient-derived iPSC by Cas9 nickase. Scientific reports. 2016;6:38198.

Borger AK, Eicke D, Wolf C, Gras C, Aufderbeck S, Schulze K, Engels L, Eiz-Vesper B, Schambach A, Guzman CA, Lachmann N, Moritz T, Martin U, Blasczyk R, Figueiredo C. Generation of HLA-universal iPSCs-derived megakaryocytes and platelets for survival under refractoriness conditions. Molecular medicine. 2016;22.

2015

Stahlhut M, Schwarzer A, Eder M, Yang M, Li Z, Morgan M, Schambach A, Kustikova OS. Lentiviral vector system for coordinated constitutive and drug controlled tetracycline-regulated gene co-expression. Biomaterials. 2015;63:189-201.

Lachmann N, Brennig S, Hillje R, Schermeier H, Phaltane R, Dahlmann J, Gruh I, Heinz N, Schiedlmeier B, Baum C, Moritz T. Tightly regulated 'all-in-one' lentiviral vectors for protection of human hematopoietic cells from anticancer chemotherapy. Gene therapy. 2015;22(11):883-92.

Dreyer AK, Hoffmann D, Lachmann N, Ackermann M, Steinemann D, Timm B, Siler U, Reichenbach J, Grez M, Moritz T, Schambach A, Cathomen T. TALEN-mediated functional correction of X-linked chronic granulomatous disease in patient-derived induced pluripotent stem cells. Biomaterials. 2015;69:191-200.

Brennig S, Lachmann N, Buchegger T, Hetzel M, Schambach A, Moritz T. “Chemoprotection of murine hematopoietic cells by combined gene transfer of cytidine deaminase (CDD) and multidrug resistance 1 gene (MDR1)”. Journal of Experimental & Clinical Cancer Research. 2015.

Suerth JD, Morgan MA, Kloess S, Heckl D, Neudorfl C, Falk CS, Koehl U, Schambach A. Efficient Generation of Gene-Modified Human Natural Killer Cells Via Alpharetroviral Vectors. J Mol Med (Berl). 2015.

Stahlhut M, Schwarzer A, Eder M, Yang M, Li Z, Morgan M, Schambach A, Kustikova OS. Lentiviral Vector System for Coordinated Constitutive and Drug Controlled Tetracycline-Regulated Gene Co-Expression. Biomaterials. 2015;63:189-201.

Schwarzer A, Holtmann H, Brugman M, Meyer J, Schauerte C, Zuber J, Steinemann D, Schlegelberger B, Li Z, Baum C. Hyperactivation of Mtorc1 and Mtorc2 by Multiple Oncogenic Events Causes Addiction to Eif4e-Dependent Mrna Translation in T-Cell Leukemia. Oncogene. 2015;34(27):3593-604.

Schott JW, Jaeschke NM, Hoffmann D, Maetzig T, Ballmaier M, Godinho T, Cathomen T, Schambach A. Deciphering the Impact of Parameters Influencing Transgene Expression Kinetics after Repeated Cell Transduction with Integration-Deficient Retroviral Vectors. Cytometry A. 2015;87(5):405-18.

Rissone A, Weinacht KG, la Marca G, Bishop K, Giocaliere E, Jagadeesh J, Felgentreff K, Dobbs K, Al-Herz W, Jones M, Chandrasekharappa S, Kirby M, Wincovitch S, Simon KL, Itan Y, DeVine A, Schlaeger T, Schambach A, Sood R, Notarangelo LD, Candotti F. Reticular Dysgenesis-Associated Ak2 Protects Hematopoietic Stem and Progenitor Cell Development from Oxidative Stress. J Exp Med. 2015;212(8):1185-202.

Ripperger T, Manukjan G, Meyer J, Wolter S, Schambach A, Bohne J, Modlich U, Li Z, Skawran B, Schlegelberger B, Steinemann D. The Heteromeric Transcription Factor Gabp Activates the Itgam/Cd11b Promoter and Induces Myeloid Differentiation. Biochim Biophys Acta. 2015;1849(9):1145-54.

Regelin M, Blume J, Pommerencke J, Vakilzadeh R, Witzlau K, Lyszkiewicz M, Zietara N, Saran N, Schambach A, Krueger A. Responsiveness of Developing T Cells to Il-7 Signals Is Sustained by Mir-17 Approximately 92. J Immunol. 2015;195(10):4832-40. Epub 2015/10/18.

Rahman SH, Kuehle J, Reimann C, Mlambo T, Alzubi J, Maeder ML, Riedel H, Fisch P, Cantz T, Rudolph C, Mussolino C, Joung JK, Schambach A, Cathomen T. Rescue of DNA-Pk Signaling and T-Cell Differentiation by Targeted Genome Editing in a Prkdc Deficient Ipsc Disease Model. PLoS Genet. 2015;11(5):e1005239.

Muller-Kuller U, Ackermann M, Kolodziej S, Brendel C, Fritsch J, Lachmann N, Kunkel H, Lausen J, Schambach A, Moritz T, Grez M. A Minimal Ubiquitous Chromatin Opening Element (Ucoe) Effectively Prevents Silencing of Juxtaposed Heterologous Promoters by Epigenetic Remodeling in Multipotent and Pluripotent Stem Cells. Nucleic Acids Res. 2015;43(3):1577-92.

Manukjan G, Ripperger T, Santer L, von Neuhoff N, Ganser A, Schambach A, Schlegelberger B, Steinemann D. Expression of the Ets Transcription Factor Gabpalpha Is Positively Correlated to the Bcr-Abl1/Abl1 Ratio in Cml Patients and Affects Imatinib Sensitivity in Vitro. Exp Hematol. 2015;43(10):880-90. Epub 2015/06/15.

Lyszkiewicz M, Zietara N, Fohse L, Puchalka J, Diestelhorst J, Witzlau K, Prinz I, Schambach A, Krueger A. Limited Niche Availability Suppresses Murine Intrathymic Dendritic-Cell Development from Noncommitted Progenitors. Blood. 2015;125(3):457-64.

Lachmann N, Czarnecki K, Brennig S, Phaltane R, Heise M, Heinz N, Kempf H, Dilloo D, Kaever V, Schambach A, Heuser M, Moritz T. Deoxycytidine-Kinase Knockdown as a Novel Myeloprotective Strategy in the Context of Fludarabine, Cytarabine or Cladribine Therapy. Leukemia. 2015;29(11):2266-9. Epub 2015/04/30.

Lachmann N, Brennig S, Hillje R, Schermeier H, Phaltane R, Dahlmann J, Gruh I, Heinz N, Schiedlmeier B, Baum C, Moritz T. Tightly Regulated 'All-in-One' Lentiviral Vectors for Protection of Human Hematopoietic Cells from Anticancer Chemotherapy. Gene Ther. 2015;22(11):883-92.

Lachmann N, Ackermann M, Frenzel E, Liebhaber S, Brennig S, Happle C, Hoffmann D, Klimenkova O, Luttge D, Buchegger T, Kuhnel MP, Schambach A, Janciauskiene S, Figueiredo C, Hansen G, Skokowa J, Moritz T. Large-Scale Hematopoietic Differentiation of Human Induced Pluripotent Stem Cells Provides Granulocytes or Macrophages for Cell Replacement Therapies. Stem Cell Reports. 2015;4(2):282-96.

Hoseini SS, Hapke M, Herbst J, Wedekind D, Baumann R, Heinz N, Schiedlmeier B, Vignali DA, van den Brink MR, Schambach A, Blazar BR, Sauer MG. Inducible T-Cell Receptor Expression in Precursor T Cells for Leukemia Control. Leukemia. 2015;29(7):1530-42.

Hoffmann D, Gohring G, Heuser M, Ganser A, Schambach A, Morgan MA. Letter to the Editor: Production of Mature Healthy Hematopoietic Cells from Induced Pluripotent Stem Cells Derived from an Aml Diagnostic Sample Containing the T(8;21) Translocation. Stem Cells. 2015.

Heinz N, Ehrnstrom B, Schambach A, Schwarzer A, Modlich U, Schiedlmeier B. Comparison of Different Cytokine Conditions Reveals Resveratrol as a New Molecule for Ex Vivo Cultivation of Cord Blood-Derived Hematopoietic Stem Cells. Stem Cells Transl Med. 2015;4(9):1064-72. Epub 2015/07/15.

Dreyer AK, Hoffmann D, Lachmann N, Ackermann M, Steinemann D, Timm B, Siler U, Reichenbach J, Grez M, Moritz T, Schambach A, Cathomen T. Talen-Mediated Functional Correction of X-Linked Chronic Granulomatous Disease in Patient-Derived Induced Pluripotent Stem Cells. Biomaterials. 2015;69:191-200.

Dobbs K, Dominguez Conde C, Zhang SY, Parolini S, Audry M, Chou J, Haapaniemi E, Keles S, Bilic I, Okada S, Massaad MJ, Rounioja S, Alwahadneh AM, Serwas NK, Capuder K, Ciftci E, Felgentreff K, Ohsumi TK, Pedergnana V, Boisson B, Haskologlu S, Ensari A, Schuster M, Moretta A, Itan Y, Patrizi O, Rozenberg F, Lebon P, Saarela J, Knip M, Petrovski S, Goldstein DB, Parrott RE, Savas B, Schambach A, Tabellini G, Bock C, Chatila TA, Comeau AM, Geha RS, Abel L, Buckley RH, Ikinciogullari A, Al-Herz W, Helminen M, Dogu F, Casanova JL, Boztug K, Notarangelo LD. Inherited Dock2 Deficiency in Patients with Early-Onset Invasive Infections. N Engl J Med. 2015;372(25):2409-22.

Ackermann M, Liebhaber S, Klusmann JH, Lachmann N. Lost in Translation: Pluripotent Stem Cell-Derived Hematopoiesis. EMBO Mol Med. 2015;7(11):1388-402.

2014

Zwingenberger S, Yao Z, Jacobi A, Vater C, Valladares RD, Li C, Nich C, Rao AJ, Christman JE, Antonios JK, Gibon E, Schambach A, Maetzig T, Goodman SB, Stiehler M. Enhancement of Bmp-2 Induced Bone Regeneration by Sdf-1alpha Mediated Stem Cell Recruitment. Tissue Eng Part A. 2014;20(3-4):810-8.

Zhang H, Goudeva L, Immenschuh S, Schambach A, Skokowa J, Eiz-Vesper B, Blasczyk R, Figueiredo C. Mir-155 Is Associated with the Leukemogenic Potential of the Class Iv Granulocyte Colony-Stimulating Factor Receptor in Cd34(+) Progenitor Cells. Mol Med. 2014;20:736-46. Epub 2015/03/03.

Wunderlich S, Kircher M, Vieth B, Haase A, Merkert S, Beier J, Gohring G, Glage S, Schambach A, Curnow EC, Paabo S, Martin U, Enard W. Primate Ips Cells as Tools for Evolutionary Analyses. Stem Cell Res. 2014;12(3):622-9.

Thomay K, Schienke A, Vajen B, Modlich U, Schambach A, Hofmann W, Schlegelberger B, Gohring G. Chromosomal Instability and Telomere Shortening in Long-Term Culture of Hematopoietic Stem Cells: Insights from a Cell Culture Model of Rps14 Haploinsufficiency. Cytogenet Genome Res. 2014;142(1):14-20.

Suzuki T, Arumugam P, Sakagami T, Lachmann N, Chalk C, Sallese A, Abe S, Trapnell C, Carey B, Moritz T, Malik P, Lutzko C, Wood RE, Trapnell BC. Pulmonary Macrophage Transplantation Therapy. Nature. 2014;514(7523):450-4.

Suerth JD, Labenski V, Schambach A. Alpharetroviral Vectors: From a Cancer-Causing Agent to a Useful Tool for Human Gene Therapy. Viruses. 2014;6(12):4811-38.

Rothe M, Schambach A, Biasco L. Safety of Gene Therapy: New Insights to a Puzzling Case. Curr Gene Ther. 2014;14(6):429-36.

Phaltane R, Lachmann N, Brennig S, Ackermann M, Modlich U, Moritz T. Lentiviral Mgmt(P140k)-Mediated in Vivo Selection Employing a Ubiquitous Chromatin Opening Element (A2ucoe) Linked to a Cellular Promoter. Biomaterials. 2014;35(25):7204-13. Epub 2014/05/31.

Maetzig T, Kuehle J, Schwarzer A, Turan S, Rothe M, Chaturvedi A, Morgan M, Ha TC, Heuser M, Hammerschmidt W, Baum C, Schambach A. All-in-One Inducible Lentiviral Vector Systems Based on Drug Controlled Flp Recombinase. Biomaterials. 2014;35(14):4345-56.

Liu L, Xu Y, He M, Zhang M, Cui F, Lu L, Yao M, Tian W, Benda C, Zhuang Q, Huang Z, Li W, Li X, Zhao P, Fan W, Luo Z, Li Y, Wu Y, Hutchins AP, Wang D, Tse HF, Schambach A, Frampton J, Qin B, Bao X, Yao H, Zhang B, Sun H, Pei D, Wang H, Wang J, Esteban MA. Transcriptional Pause Release Is a Rate-Limiting Step for Somatic Cell Reprogramming. Cell Stem Cell. 2014;15(5):574-88.

Limbourg A, Schnabel S, Lozanovski VJ, Napp LC, Ha TC, Maetzig T, Bauersachs J, Naim HY, Schambach A, Limbourg FP. Genetic Reporter Analysis Reveals an Expandable Reservoir of Oct4+ Cells in Adult Skin. Cell Regen (Lond). 2014;3(1):9.

Lachmann N, Happle C, Ackermann M, Luttge D, Wetzke M, Merkert S, Hetzel M, Kensah G, Jara-Avaca M, Mucci A, Skuljec J, Dittrich AM, Pfaff N, Brennig S, Schambach A, Steinemann D, Gohring G, Cantz T, Martin U, Schwerk N, Hansen G, Moritz T. Gene Correction of Human Induced Pluripotent Stem Cells Repairs the Cellular Phenotype in Pulmonary Alveolar Proteinosis. Am J Respir Crit Care Med. 2014;189(2):167-82.

Kustikova OS, Stahlhut M, Ha TC, Scherer R, Schambach A, Baum C. Dose Response and Clonal Variability of Lentiviral Tetracycline-Regulated Vectors in Murine Hematopoietic Cells. Exp Hematol. 2014;42(7):505-15 e7.

Kuehle J, Turan S, Cantz T, Hoffmann D, Suerth JD, Maetzig T, Zychlinski D, Klein C, Steinemann D, Baum C, Bode J, Schambach A. Modified Lentiviral Ltrs Allow Flp Recombinase-Mediated Cassette Exchange and in Vivo Tracing of "Factor-Free" Induced Pluripotent Stem Cells. Mol Ther. 2014;22(5):919-28.

Happle C, Lachmann N, Skuljec J, Wetzke M, Ackermann M, Brennig S, Mucci A, Jirmo AC, Groos S, Mirenska A, Hennig C, Rodt T, Bankstahl JP, Schwerk N, Moritz T, Hansen G. Pulmonary Transplantation of Macrophage Progenitors as Effective and Long-Lasting Therapy for Hereditary Pulmonary Alveolar Proteinosis. Sci Transl Med. 2014;6(250):250ra113.

Haemmerle R, Phaltane R, Rothe M, Schroder S, Schambach A, Moritz T, Modlich U. Clonal Dominance with Retroviral Vector Insertions near the Angpt1 and Angpt2 Genes in a Human Xenotransplant Mouse Model. Mol Ther Nucleic Acids. 2014;3:e200.

Hacein-Bey-Abina S, Pai SY, Gaspar HB, Armant M, Berry CC, Blanche S, Bleesing J, Blondeau J, de Boer H, Buckland KF, Caccavelli L, Cros G, De Oliveira S, Fernandez KS, Guo D, Harris CE, Hopkins G, Lehmann LE, Lim A, London WB, van der Loo JC, Malani N, Male F, Malik P, Marinovic MA, McNicol AM, Moshous D, Neven B, Oleastro M, Picard C, Ritz J, Rivat C, Schambach A, Shaw KL, Sherman EA, Silberstein LE, Six E, Touzot F, Tsytsykova A, Xu-Bayford J, Baum C, Bushman FD, Fischer A, Kohn DB, Filipovich AH, Notarangelo LD, Cavazzana M, Williams DA, Thrasher AJ. A Modified Gamma-Retrovirus Vector for X-Linked Severe Combined Immunodeficiency. N Engl J Med. 2014;371(15):1407-17.

Braun CJ, Boztug K, Paruzynski A, Witzel M, Schwarzer A, Rothe M, Modlich U, Beier R, Gohring G, Steinemann D, Fronza R, Ball CR, Haemmerle R, Naundorf S, Kuhlcke K, Rose M, Fraser C, Mathias L, Ferrari R, Abboud MR, Al-Herz W, Kondratenko I, Marodi L, Glimm H, Schlegelberger B, Schambach A, Albert MH, Schmidt M, von Kalle C, Klein C. Gene Therapy for Wiskott-Aldrich Syndrome--Long-Term Efficacy and Genotoxicity. Sci Transl Med. 2014;6(227):227ra33.

Bobis-Wozowicz S, Galla M, Alzubi J, Kuehle J, Baum C, Schambach A, Cathomen T. Non-Integrating Gamma-Retroviral Vectors as a Versatile Tool for Transient Zinc-Finger Nuclease Delivery. Sci Rep. 2014;4:4656.

Ackermann M, Lachmann N, Hartung S, Eggenschwiler R, Pfaff N, Happle C, Mucci A, Gohring G, Niemann H, Hansen G, Schambach A, Cantz T, Zweigerdt R, Moritz T. Promoter and Lineage Independent Anti-Silencing Activity of the A2 Ubiquitous Chromatin Opening Element for Optimized Human Pluripotent Stem Cell-Based Gene Therapy. Biomaterials. 2014;35(5):1531-42.

2013

Zwingenberger S, Yao Z, Jacobi A, Vater C, Valladares RD, Li C, Nich C, Rao AJ, Christman JE, Antonios JK, Gibon E, Schambach A, Matzig T, Gunther KP, Goodman SB, Stiehler M. Stem Cell Attraction Via Sdf-1alpha Expressing Fat Tissue Grafts. J Biomed Mater Res A. 2013;101(7):2067-74.

Wolf S, Rudolph C, Morgan M, Busche G, Salguero G, Stripecke R, Schlegelberger B, Baum C, Modlich U. Selection for Evi1 Activation in Myelomonocytic Leukemia Induced by Hyperactive Signaling through Wild-Type Nras. Oncogene. 2013;32(25):3028-38.

Sundarasetty BS, Singh VK, Salguero G, Geffers R, Rickmann M, Macke L, Borchers S, Figueiredo C, Schambach A, Gullberg U, Provasi E, Bonini C, Ganser A, Woelfel T, Stripecke R. Lentivirus-Induced Dendritic Cells for Immunization against High-Risk Wt1(+) Acute Myeloid Leukemia. Hum Gene Ther. 2013;24(2):220-37.

Stein S, Scholz S, Schwable J, Sadat MA, Modlich U, Schultze-Strasser S, Diaz M, Chen-Wichmann L, Muller-Kuller U, Brendel C, Fronza R, Kaufmann KB, Naundorf S, Pech NK, Travers JB, Matute JD, Presson RG, Jr., Sandusky GE, Kunkel H, Rudolf E, Dillmann A, von Kalle C, Kuhlcke K, Baum C, Schambach A, Dinauer MC, Schmidt M, Grez M. From Bench to Bedside: Preclinical Evaluation of a Self-Inactivating Gammaretroviral Vector for the Gene Therapy of X-Linked Chronic Granulomatous Disease. Hum Gene Ther Clin Dev. 2013;24(2):86-98.

Schambach A, Zychlinski D, Ehrnstroem B, Baum C. Biosafety Features of Lentiviral Vectors. Hum Gene Ther. 2013;24(2):132-42.

Schambach A, Moritz T. Toward Position-Independent Retroviral Vector Expression in Pluripotent Stem Cells. Mol Ther. 2013;21(8):1474-7.

Rothe M, Modlich U, Schambach A. Biosafety Challenges for Use of Lentiviral Vectors in Gene Therapy. Curr Gene Ther. 2013;13(6):453-68.

Rittelmeyer I, Rothe M, Brugman MH, Iken M, Schambach A, Manns MP, Baum C, Modlich U, Ott M. Hepatic Lentiviral Gene Transfer Is Associated with Clonal Selection, but Not with Tumor Formation in Serially Transplanted Rodents. Hepatology. 2013;58(1):397-408.

Pfaff N, Lachmann N, Ackermann M, Kohlscheen S, Brendel C, Maetzig T, Niemann H, Antoniou MN, Grez M, Schambach A, Cantz T, Moritz T. A Ubiquitous Chromatin Opening Element Prevents Transgene Silencing in Pluripotent Stem Cells and Their Differentiated Progeny. Stem Cells. 2013;31(3):488-99.

Mandel K, Yang Y, Schambach A, Glage S, Otte A, Hass R. Mesenchymal Stem Cells Directly Interact with Breast Cancer Cells and Promote Tumor Cell Growth in Vitro and in Vivo. Stem Cells Dev. 2013;22(23):3114-27.

Lachmann N, Brennig S, Pfaff N, Schermeier H, Dahlmann J, Phaltane R, Gruh I, Modlich U, Schambach A, Baum C, Moritz T. Efficient in Vivo Regulation of Cytidine Deaminase Expression in the Haematopoietic System Using a Doxycycline-Inducible Lentiviral Vector System. Gene Ther. 2013;20(3):298-307.

Kustikova OS, Schwarzer A, Stahlhut M, Brugman MH, Neumann T, Yang M, Li Z, Schambach A, Heinz N, Gerdes S, Roeder I, Ha TC, Steinemann D, Schlegelberger B, Baum C. Activation of Evi1 Inhibits Cell Cycle Progression and Differentiation of Hematopoietic Progenitor Cells. Leukemia. 2013;27(5):1127-38.

Kaufmann KB, Buning H, Galy A, Schambach A, Grez M. Gene Therapy on the Move. EMBO Mol Med. 2013;5(11):1642-61.

Kaufmann KB, Brendel C, Suerth JD, Mueller-Kuller U, Chen-Wichmann L, Schwable J, Pahujani S, Kunkel H, Schambach A, Baum C, Grez M. Alpharetroviral Vector-Mediated Gene Therapy for X-Cgd: Functional Correction and Lack of Aberrant Splicing. Mol Ther. 2013;21(3):648-61.

Hauber I, Hofmann-Sieber H, Chemnitz J, Dubrau D, Chusainow J, Stucka R, Hartjen P, Schambach A, Ziegler P, Hackmann K, Schrock E, Schumacher U, Lindner C, Grundhoff A, Baum C, Manz MG, Buchholz F, Hauber J. Highly Significant Antiviral Activity of Hiv-1 Ltr-Specific Tre-Recombinase in Humanized Mice. PLoS Pathog. 2013;9(9):e1003587.

Gurlevik E, Fleischmann-Mundt B, Armbrecht N, Longerich T, Woller N, Kloos A, Hoffmann D, Schambach A, Wirth TC, Manns MP, Zender L, Kubicka S, Kuhnel F. Adjuvant Gemcitabine Therapy Improves Survival in a Locally Induced, R0-Resectable Model of Metastatic Intrahepatic Cholangiocarcinoma. Hepatology. 2013;58(3):1031-41.

Gupta SS, Maetzig T, Maertens GN, Sharif A, Rothe M, Weidner-Glunde M, Galla M, Schambach A, Cherepanov P, Schulz TF. Bromo- and Extraterminal Domain Chromatin Regulators Serve as Cofactors for Murine Leukemia Virus Integration. J Virol. 2013;87(23):12721-36.

Gross B, Sgodda M, Rasche M, Schambach A, Gohring G, Schlegelberger B, Greber B, Linden T, Reinhardt D, Cantz T, Klusmann JH. Improved Generation of Patient-Specific Induced Pluripotent Stem Cells Using a Chemically-Defined and Matrigel-Based Approach. Curr Mol Med. 2013;13(5):765-76.

Grabundzija I, Wang J, Sebe A, Erdei Z, Kajdi R, Devaraj A, Steinemann D, Szuhai K, Stein U, Cantz T, Schambach A, Baum C, Izsvak Z, Sarkadi B, Ivics Z. Sleeping Beauty Transposon-Based System for Cellular Reprogramming and Targeted Gene Insertion in Induced Pluripotent Stem Cells. Nucleic Acids Res. 2013;41(3):1829-47.

Galla M, Schambach A, Baum C. Retrovirus-Based Mrna Transfer for Transient Cell Manipulation. Methods Mol Biol. 2013;969:139-61.

Eggenschwiler R, Loya K, Wu G, Sharma AD, Sgodda M, Zychlinski D, Herr C, Steinemann D, Teckman J, Bals R, Ott M, Schambach A, Scholer HR, Cantz T. Sustained Knockdown of a Disease-Causing Gene in Patient-Specific Induced Pluripotent Stem Cells Using Lentiviral Vector-Based Gene Therapy. Stem Cells Transl Med. 2013;2(9):641-54.

Brugman MH, Suerth JD, Rothe M, Suerbaum S, Schambach A, Modlich U, Kustikova O, Baum C. Evaluating a Ligation-Mediated Pcr and Pyrosequencing Method for the Detection of Clonal Contribution in Polyclonal Retrovirally Transduced Samples. Hum Gene Ther Methods. 2013;24(2):68-79.

2006 - 2012

2012

Wunderlich S, Haase A, Merkert S, Beier J, Schwanke K, Schambach A, Glage S, Gohring G, Curnow EC, Martin U. Induction of Pluripotent Stem Cells from a Cynomolgus Monkey Using a Polycistronic Simian Immunodeficiency Virus-Based Vector, Differentiation toward Functional Cardiomyocytes, and Generation of Stably Expressing Reporter Lines. Cell Reprogram. 2012;14(6):471-84.

Wiedemann A, Hemmer K, Bernemann I, Gohring G, Pogozhykh O, Figueiredo C, Glage S, Schambach A, Schwamborn JC, Blasczyk R, Muller T. Induced Pluripotent Stem Cells Generated from Adult Bone Marrow-Derived Cells of the Nonhuman Primate (Callithrix Jacchus) Using a Novel Quad-Cistronic and Excisable Lentiviral Vector. Cell Reprogram. 2012;14(6):485-96.

Wang J, Sun Q, Morita Y, Jiang H, Gross A, Lechel A, Hildner K, Guachalla LM, Gompf A, Hartmann D, Schambach A, Wuestefeld T, Dauch D, Schrezenmeier H, Hofmann WK, Nakauchi H, Ju Z, Kestler HA, Zender L, Rudolph KL. A Differentiation Checkpoint Limits Hematopoietic Stem Cell Self-Renewal in Response to DNA Damage. Cell. 2012;148(5):1001-14.

Suerth JD, Schambach A, Baum C. Genetic Modification of Lymphocytes by Retrovirus-Based Vectors. Curr Opin Immunol. 2012;24(5):598-608.

Suerth JD, Maetzig T, Brugman MH, Heinz N, Appelt JU, Kaufmann KB, Schmidt M, Grez M, Modlich U, Baum C, Schambach A. Alpharetroviral Self-Inactivating Vectors: Long-Term Transgene Expression in Murine Hematopoietic Cells and Low Genotoxicity. Mol Ther. 2012;20(5):1022-32.

Schambach A, Baum C. Vectorizing Mrna and Proteins. Curr Gene Ther. 2012;12(5):345-6.

Maetzig T, Baum C, Schambach A. Retroviral Protein Transfer: Falling Apart to Make an Impact. Curr Gene Ther. 2012;12(5):389-409.

Lesinski DA, Heinz N, Pilat-Carotta S, Rudolph C, Jacobs R, Schlegelberger B, Klump H, Schiedlmeier B. Serum- and Stromal Cell-Free Hypoxic Generation of Embryonic Stem Cell-Derived Hematopoietic Cells in Vitro, Capable of Multilineage Repopulation of Immunocompetent Mice. Stem Cells Transl Med. 2012;1(8):581-91.

Koch L, Deiwick A, Schlie S, Michael S, Gruene M, Coger V, Zychlinski D, Schambach A, Reimers K, Vogt PM, Chichkov B. Skin Tissue Generation by Laser Cell Printing. Biotechnol Bioeng. 2012;109(7):1855-63.

Geiger H, Pawar SA, Kerschen EJ, Nattamai KJ, Hernandez I, Liang HP, Fernandez JA, Cancelas JA, Ryan MA, Kustikova O, Schambach A, Fu Q, Wang J, Fink LM, Petersen KU, Zhou D, Griffin JH, Baum C, Weiler H, Hauer-Jensen M. Pharmacological Targeting of the Thrombomodulin-Activated Protein C Pathway Mitigates Radiation Toxicity. Nat Med. 2012;18(7):1123-9.

Blank U, Ehrnstrom B, Heinz N, Nilsson E, Brun A, Baum C, Schiedlmeier B, Karlsson S. Angptl4 Maintains in Vivo Repopulation Capacity of Cd34+ Human Cord Blood Cells. Eur J Haematol. 2012;89(3):198-205.

Abdollahpour H, Appaswamy G, Kotlarz D, Diestelhorst J, Beier R, Schaffer AA, Gertz EM, Schambach A, Kreipe HH, Pfeifer D, Engelhardt KR, Rezaei N, Grimbacher B, Lohrmann S, Sherkat R, Klein C. The Phenotype of Human Stk4 Deficiency. Blood. 2012;119(15):3450-7.

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