Benutzerspezifische Werkzeuge

Experimentelle Hämatologie

Staff:

– scientific lab manager
– clinical counselor






cand. med. Tobias Neidel
Katrin Navratiel (MTA)

Research Focus:

  • Regulation of the immune response by plasmacytoid dendritic cells (pDC)

Autoimmune diseases and allergies present an enormous burden for patients and public health care systems. The pathophysiology of the excessive immune response either to self antigens or to harmless environmental agents starts with a loss of tolerance mediated by dendritic cells that present antigens to naïve T cells. Here, a special type of dendritic cells – the so called plasmacytoid dendritic cells – exerts both protective and pathogenic functions.
These at first sight contradictory properties of pDCs can be explained by a novel and fundamental finding. We utilize the functional expression of the low affinity neurotrophin receptor p75NTR on human and murine pDCs in a bidirectional manner to control the immune function of pDCs itself and of downstream effector cells, the outcome of an allergic asthma and a graft-versus-host reaction (GvHD), as well as the onset of an autoimmune diabetes type I (T1D) in mice.

  • Hematopoietic stem cell migration and differentiation

Homing of hematopoietic stem cells (HSC) is thought to be a multi-step process, which is initiated by chemotactic movements through the endothelium and extracellular matrix (ECM) to the endosteal space of the bone marrow, followed by tight adhesion and proliferation of these cells in the bone marrow niche. Normal and leukemic HSC express the chemokine receptor CXCR4 and migrate towards a SDF-1 gradient into the bone marrow niche. SDF-1/CXCR4 has been proposed to function in HSC adhesion and migration by activating the expression of adhesive molecules of the integrin family.

  • Red blood cell development and differentiation

Erythropoiesis represents a tightly-regulated and complex process originating in the bone marrow from a multipotent stem cell and terminating in a mature, enucleated red blood cell (RBCs). RBCs play an essential role in carrying oxygen to tissues. In order to sustain body homeostasis, around 2 million RBCs are produced in human by erythropoiesis every second. Therefore, dysregulation of erythropoiesis and an altered red cell production can result in the development of thalassemia syndromes, inherited bone marrow failure as well as in anemias.
Our group recently discovered a protein, which is specifically expressed in erythropoietic progenitor cells affecting the maturation from reticulocytes to red blood cells. Hence, we aim to elucidate its protein functions in RBC differentiation and maturation and are interested how the protein or its metabolic products affect cellular and physical properties of RBCs.

Expertise:

  • Retroviral based gene transfer in human or murine primary cells
  • Gene silencing by RNAi technology
  • Isolation and transplantation of primary cells and cell lines

Current research projects:

  • Characterization of the Transmembrane protein 56 and its function in erythropoietic stem cell migration and erythropoiesis (DFG; Ralf Wiedemuth)
  • p75, dendritic cells (Dr. Robert-Pfleger Stiftung; Sebastian Thieme)
  • NGF-vermittelte Proteinphosphorylierungen in plasmazytoiden dendritischen Zellen (Else Kröner Stiftung; Benjamin Dorschner)
  • Immunologische Kontrolle der Tumorgenese (Meddrive; Lukas Galow)
  • Einfluss der p75NTR/pDC Achse auf die Pathogenes eines Typ-1-Diabetes (Meddrive; Katja Rüger)
  • pDC-spezifische Modulation von p75NTR im Rahmen der GvHD (Meddrive; Ann-Christin Funke)
  • Steuerung der T-Zellfunktion in der Pathogenese eines Typ-1-Diabetes (Meddrive; Franz Mierke)

Contact:

Dr. rer. nat. Sebastian Thieme
Klinik und Poliklinik für Kinder- und Jugendmedizin
Labor Klinische Forschung - AG Experimentelle Hämatologie
Universitätsklinikum Carl Gustav Carus, TU Dresden
Fetscherstr. 74, 01307 Dresden

Location:

Haus 21, 1. UG

Fon:

+49 (351) 458 6885

Funding:

DFG / SFB
DFG
BMBF
Stiftung Hochschulmedizin
Dr. Robert-Pfleger Stiftung
Sächsische Aufbaubank
Sächsisches Ministerium für Höhere Bildung und Kunst
Deutsche Krebshilfe
CRTD
Medizinische Fakultät der TU Dresden
Else-Kröner-Stiftung

Publications:

Moghaddas F, Zeng P, Zhang Y, Schützle H, Brenner S, Hofmann SR, Berner R, Zhao Y, Lu B, Chen X, Zhang L, Cheng S, Winkler S, Lehmberg K, Canna SW, Czabotar P, Wicks IP, De Nardo D, Hedrich CM, Zeng H, Masters S; Autoinflammation and macrophage activation syndrome caused by mutation in the leucine rich repeat domain of NLRC4 delineates mechanisms of inflammasome assembly. J Allergy Clin Immunol. 2018 May 17. pii: S0091-6749(18)30710-3. IF 13.258

Stopp S, Bornhäuser M, Ugarte F, Wobus M, Kuhn M, Thieme S*, Brenner S*. Expression of the melanoma cell adhesion molecule in human mesenchymal stromal cells regulates proliferation, differentiation, and maintenance of hematopoietic stem and progenitor cells. Haematologica 2013 Apr;98(4):505-13. *both authors contributed equally. IF 9.09

Laugsch M, Rostovskaya M, Velychko S, Richter C, Zimmer A, Klink B, Schröck E, Haase M, Neumann K, Thieme S, Roesler J, Brenner S#, Anastassiadis K#. Functional restoration of gp91phox-oxidase activity by BAC transgenesis and gene targeting in X-linked chronic granulomatous disease iPSCs. Mol Ther. 2016 Apr;24(4):812-22. #shared last authorship. IF 7.008

Richter C, Thieme S, Bandola J, Laugsch M, Anastassiadis K, Brenner S. Generation of inducible immortalized dendritic cells with proper immune function in vitro and in vivo. PLOS ONE 2013, Apr 8(4): e62621. IF ‎2.766

Jacobi A, Thieme S, Lehmann R, Ugarte F, Malech HL, Koch S, Thiede C, Müller K, Bornhäuser M, Ryser M, Brenner S. Impact of CXCR4 inhibition on FLT3-ITD positive human AML blasts. Exp Hematol. 2010;38:180-190. IF 2.436

Ryser MF, Ugarte F, Thieme S, Gentsch M, Bornhäuser M, Roesen-Wolff A, Brenner S. mRNA transfection of a CXCR4-GFP fusion protein - generated by a simple three step PCR protocol - results in efficient migration of primary mesenchymal stem cells. Tissue Eng Part C Methods. 2008 Sep;14,179-84. IF 3.508

Bandoła J, Richter C, Ryser M, Jamal A, Ashton MP, von Bonin M, Kuhn M, Dorschner B, Alexopoulou D, Navratiel K, Roeder I, Dahl A, Hedrich CM, Bonifacio E, Brenner S*, Thieme S*. Neurotrophin receptor p75NTR regulates immune function of plasmacytoid dendritic cells. Frontiers in Immunology 2017 Aug 17;8:981. *both authors contributed equally. IF 6.429

Ugarte F, Ryser M, Thieme S, Fierro FA, Navratiel K, Bornhäuser M, Brenner S. Notch signaling enhances osteogenic differentiation while inhibiting adipogenesis in primary human bone marrow stromal cells. Exp Hematol. 2009 Jul;37(7):867-875. IF 2.436

Brenner S, Ryser MF, Choi U, Whiting-Theobald N, Kuhlisch E, Linton G, Kang E, Lehmann R, Rosen-Wolff A, Rudikoff AG, Farese AM, MacVittie TJ, Roesler J, Horwitz ME, Malech HL. Polyclonal long-term MFGS-gp91phox marking in rhesus macaques after non-myeloablative transplantation with transduced autologous peripheral blood progenitor cells. Mol Ther. 2006 Aug;14(2):202-11. IF 7.008

Wermke M, Camgoz A, Paszkowski-Rogacz M, Thieme S, von Bonin M, Dahl A, Platzbecker U, Theis M, Ehninger G, Brenner S, Bornhäuser M, Buchholz F. RNAi profiling of primary human AML cells identifies ROCK1 as a therapeutic target and nominates fasudil as an antileukemic drug. Blood. 2015 Jun 11;125(24):3760-8. IF 15.132

Ryser MF, Ugarte F, Gentsch M, Lehmann R, Bornhäuser M, Brenner S. S1P1 overexpression stimulates S1P dependent chemotaxis of human hematopoietic stem cells but strongly inhibits SDF-1/CXCR4 dependent migration and in vivo homing. Mol Immunol. 2008 Nov;46,166-71. IF 3.188

Thieme S, Ryser M, Gentsch M, Brenner S, Stiehler M, Rölfing J, Gelinsky M, Rösen-Wolff A. Stromal derived factor-1a (SDF-1α) directed chemoattraction of transiently CXCR4 overexpressing mesenchymal stem cells into functionalised three-dimensional biomimetic scaffolds. Tissue Eng. 2009 Dec;15(4):687-96. IF 3.508

Richter C, Thieme S, Holzbaur A, Wiedemuth R, Binner A, Navratiel K, Konstantinos A, Brenner S. The Dox-pDC - a murine conditionally immortalized plasmacytoid dendritic cell line with native immune profile. PLOS ONE 2018 Feb 28;13(2):e0192437. IF ‎2.766

Thieme S, Gyárfás T, Richter C, Ozhan G, Fu J, Alexopoulou D, Muders MH, Michalk I, Jakob C, Dahl A, Klink B, Bandola J, Bachmann M, Schröck E, Buchholz F, Stewart AF, Weidinger G, Anastassiadis K, Brenner S. The histone demethylase UTX regulates stem cell migration and hematopoiesis. Blood 2013 Mar;121(13):2462-73. IF 15.132

The late dividing population of gamma-retroviral vector transduced human mobilized peripheral blood progenitor cells contributes most to gene-marked cell engraftment in nonobese diabetic/severe combined immunodeficient mice. Brenner S, Ryser MF, Whiting-Theobald NL, Gentsch M, Linton GF, Malech HL. Stem Cells. 2007 Jul;25(7):1807-13. IF 5.587

Thieme S, Wiedemuth R, Navratiel K, Dorschner B, Brenner S. UTX - moonlighting in the cytoplasm? The International Journal of Biochemistry & Cell Biology 2018 Apr;97:78-82. IF 3.247