Abteilung für Transfusionsmedizin, Zelltherapeutika und Hämostaseologie
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AG Wichmann

AG Wichmann_LMU_2024
AG Wichmann Group Members

Group Members (left to right):

PD Dr. med. Christian Wichmann, PI

Sophie Kreissig, M. Sc. PhD student

Dr. phil. nat. Linping Chen-Wichmann, Lab-Manager

Dr. rer. nat. Roland Windisch, PostDoc

Stefani Xhaxho, MD student


Experimental Cell Therapy & Hematology

Scope:

We use human primary cell models to study oncogenic expansion of progenitor cells though transcription factors like RUNX1-ETO and MLL-ENL. A second project is the development of retroviral vectors for efficient and safe CAR T cell production. 

Methods:

Culture of human CD34+ stem-/progenitor cells. Retroviral transduction and expression of inducible transcription factors. Long term cultivation in liquid cultures. 

Current Research Topics

AG Wichmann_LMU_2024
Fluorescence microscopy of engulfed tumor cells after co-incubation with CD34+ stem/progenitor cell derived macrophages.
  • Manufacturing of engineered immune cells in vitro In the raising field of cell therapy, we focus on engineering both Chimeric Antigen Receptor (CAR) T cells as well as macrophages in vitro. Our scope is to modify the cells in a way to ensure both strong anti-cancer effects as wells as tight controllability to prevent unwanted side effects. For this, we develop new retro- and lentiviral vectors to stably express transgenes of interest. Furthermore, we aim to establish new methods to warrant large-scale production of therapeutic immune cells ex vivo. 
Urheberschaft ungeklärt

Cooperation between the leukemic fusion protein MLL-ENL and interaction partners to drive proliferation.

  • Investigating the role of transcription factors in leukemic transformation. During leukemogenesis, transcription factors are often disrupted and lead to uncontrolled proliferation of immature progenitor cells. Two prominent such transcription factors which originate from chromosomal translocation are RUNX1-ETO and MLL-ENL. To study their oncogenic expansion capacity and to reveal novel interaction partners, we use retro- and lentiviral vectors to overexpress specific genes of interest in healthy human progenitor cells. Further genetic tools and pharmacological inhibition are utilized to test potentional vulnerabilities of diseased cells in translational approaches. 

Literature:

  • Windisch R, Soliman S, Hoffmann A, Chen-Wichmann L, Danese A, Vosberg S, Bravo J, Lutz S, Kellner C, Fischer A, Gebhard C, Redondo Monte E, Hartmann L, Schneider S, Beier F, Strobl CD, Weigert O, Peipp M, Schündeln M, Stricker SH, Rehli M, Bernhagen J, Humpe A, Klump H, Brendel C, Krause DS, Greif PA, Wichmann C. Engineering an inducible leukemia-associated fusion protein enables large-scale ex vivo production of functional human phagocytes. Proc Natl Acad Sci U S A. 2024 Jun 18;121(25):e2312499121. doi: 10.1073/pnas.2312499121. Epub 2024 Jun 10.
  • Xhaxho S, Chen-Wichmann L, Kreissig S, Windisch R, Gottschlich A, Nandi S, Schabernack S, Kohler I, Kellner C, Kobold S, Humpe A, and Wichmann C. Efficient Chimeric Antigen Receptor T-cell generation starting with leukoreduction system chambers of thrombocyte apheresis sets. Transfusion Medicine and Hemotherapy. DOI: 10.1159/000532130
  • Windisch R, Kreißig S, Wichmann C: Defined Leukemic CD34+ Liquid Cultures to Study HDAC/Transcriptional Repressor Complexes. Methods in Molecular Biology, Springer Nature 2023;2589:27-49.
  • Chen-Wichmann L, Shvartsman M, Preiss C, Hockings C, Windisch R, Redondo-Monte E, Leupolt G, Spiekermann K, Lausen J, Brendel C, Grez M, Greif P, Wichmann C: Compatibility of RUNX1/ETO fusion protein modules driving CD34+ human progenitor cell expansion. Oncogene. 2019, Jan;38(2):261-272.
  • Schanda J, Chun-Wie L, Wohlan K, Müller-Kuller U, Kunkel H, Quagliano-Lo Coco I, Stein S, Metz A, Koch J, Lausen J, Medyouf H, Gohlke H, Heuser M, Eder M, Grez M, Scherr M, and Wichmann C. Suppression of RUNX1/ETO oncogenic activity by a small molecule inhibitor of NHR2 tetramerization. Haematologica. 2017 May;102(5):e170-e174.
  • Ponnusamy K, Kohrs N, Ptasinska A, Assi SA, Herold T, Hiddemann W, Lausen J, Bonifer C, Henschler R, Wichmann C. RUNX1/ETO blocks selectin-mediated adhesion via epigenetic silencing of PSGL-1. Oncogenesis. 2015 Apr 13;4:e146.
  • Tobias Zeller, Sebastian Lutz, Münnich I, Windisch R, Hilger P, Herold T, Tahiri N, Banck J, Weigert O, Moosmann A, von Bergwelt-Baildon M, Bruns H, Wichmann C, Valerius T, Schewe D, Peipp M, Rösner T, Humpe A, and Kellner C: Dual Checkpoint Blockade of CD47 and LILRB1 Enhances CD20 Antibody-Dependent Phagocytosis of Lymphoma Cells by Macrophages. Frontiers Immunology. 2022.
  • Redondo Monte E, Leubolt G, Windisch R, Kerbs P, Dutta S, Landspersky T, Istvánffy R, Oostendorp RAJ, Chen-Wichmann L, Herold T, Cusan M, Schotta G, Wichmann C, Greif PA. Specific effects of somatic GATA2 zinc finger mutations on erythroid differentiation. Exp Hematol. 2022 Apr;108:26-35.
  • Redondo Monte E, Wilding A, Leubolt G, Kerbs P, Bagnoli J, Hartmann L, Hiddemann W, Chen-Wichmann L, Krebs S, Blum H, Cusan M, Vick B, Jeremias I, Enard W, Wichmann C, Greif PA. ZBTB7A prevents RUNX1-RUNX1T1 dependent clonal expansion of human hematopoietic progenitor cells. Oncogene. Oncogene. 2020 Apr;39(15):3195-3205.