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Medizinische Hochschule Hannover | Hämatologie, Hämostaseologie und Onkologie | Carl-Neuberg-Str.1 | 30625 Hannover | Tel.:(+49) 0511-532-0

Leukemogenesis and Molecular Therapy

Principal Investigator

  

Prof. Zhixiong Li, MD

 

Kontakt / Contact

 

Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation

OE 6860

Building K04, Level H0, Room 1180

Medizinische Hochschule Hannover

Carl-Neuberg-Str. 1

30625 Hannover

Tel: +49-511-532 9383

Fax: +49-511-532-18586

E-Mail: li.zhixiongmh-hannover.de

 

Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation

Hannover Medical School

Carl-Neuberg-Str. 1

30625 Hannover

Germany

Phone: 0049 511-532 9383

Fax:      0049 511-532 18586

E-Mail: li.zhixiong@mh-hannover.de

Stellenausschreibung PhD-Student

 

Wir suchen für das Projekt "Role of fibroblast growth factor receptors in the pathogenesis of acute myeloid leukemia (AML) “

 

eine/einen PhD-Studenten/-in zum nächstmöglichen Zeitpunkt.

 

Nähere Informationen finden Sie hier !

 

Seeking doctoral students

We are seeking MD or PhD students for our ongoing projects. Doctoral students will get a stipend (usually 1200€/month) from our projects, limited first for one year (with the opportunity to prolong). If interested, please contact Prof. Li (see above).

Forschungsschwerpunkte / Research Interest

 

Our group is interested in understanding how receptor protein tyrosine kinases (PTKs) contribute to development of leukemia and systemic mastocytosis. Receptor PTKs are often deregulated in human cancers and may be important for self-renewal of cancer stem cells. Thus, receptor PTKs represent attractive targets for selective molecular therapy. Our work has focused in part on the neurotrophin receptors and FLT3 signaling pathways. Neurotrophins (NTs, e.g. BDNF=brain-derived neurotrophic factor) and their receptors play a key role in neurogenesis and survival. The TRK (tropomyosin-related kinase) receptor PTKs (TRKA, TRKB, TRKC) are high affinity NT-receptors that are expressed in a variety of human tissues. However, we and others have recently obtained evidence for a potential involvement of this receptor system in leukemia and mast cell disorders. To study the TRK pathway and other important cellular networks, we have currently established mouse models for leukemogenesis through altered TRK signaling and performed molecular analysis in primary samples from patients with acute leukemia. Our data suggested that TRKs and their downstream signaling partners (e.g. mTOR) might serve as attractive therapeutic targets in acute leukemias and mastocytosis. Moreover, Prof. Li has long-term experiences in the development of retroviral vector systems for gene transfer into hematopoietic stem cells (HSCs) and preclinical gene therapy trials.

Development of acute myeloid leukemia in mouse #681 transplanted with TRKB and BDNF modified hematopoietic cells. (Left panel) FACS analysis showing co-expression of TRKB and BDNF before transplantation and in myeloid blasts isolated from the animal. (Right panel) Extensive infiltration of leukemic cells in liver and spleen.

 

Development of SM in mice transplanted with TRKB- and BDNF-modified hematopoietic stem/progenitor cells. (A, B) Accumulation of mast cells in liver (x100, x400). (C, D) Sections of spleen showing infiltration of mast cells in the red pulp of spleen (x100, x400). (E) Cytospin of spleen demonstrating mature mast cells with abundant cytoplasm filled with granules (x1000). (F) Section of bone marrow showing extensive infiltration of mast cells in sternum and osteosclerosis (x100)

Aktuelle Förderungen / Grants

 

Our research has been funded by

 

          Deutsche Forschungsgemeinschaft (DFG),

          Deutsche Josè Carreras Leukämie-Stiftung e.V.,

          Alfred & Angelika Gutermuth-Stiftung

Ausgewählte Literatur / Selected Publications

 

Pan Z, Yang M, Huang K, Büsche G, Glage S, Ganser A, Li Z. Flow cytometric characterization of acute leukemia reveals a distinctive “blast gate” of murine T-lymphoblastic leukemia/lymphoma. Oncotarget 2018; 9:2320-2328.

 

Yang M, Pan Z, Huang K, Büsche G, Feuerhake F, Chaturvedi A, Nie D, Heuser M, Thol F, von Neuhoff N, Ganser A, Li Z. Activation of TRKA receptor elicits mastocytosis in mice and is involved in the development of resistance to KIT-targeted therapy. Oncotarget 2017; 8:73871-73883.

 

Huang K, Yang M, Pan Z, Heidel FH, Scherr M,  Eder M, Fischer T,  Büsche G, Welte K, von Neuhoff N, Ganser A, Li Z. Leukemogenic potency of the novel FLT3-N676K mutant. Annals of Hematology 2016 95(5):783-91.

 

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 Sep;63:189-201.

 

Yang M, Huang K, Büsche G, Ganser A, Li Z. Activation of TRKB receptor in murine hematopoietic stem/progenitor cells induced mastocytosis. Blood. 2014;124:1196-7.

 

Yang M, Büsche G, Ganser A, Li Z. Morphology and quantitative composition of hematopoietic cells in murine bone marrow and spleen of healthy subjects. Annals of Hematology 2013; 92(5):587-94.

 

Skokowa J, Klimiankou M, Klimenkova O, Lan D, Gupta K, Hussein K, Carrizosa E, Kusnetsova I, Li Z, Sustmann C, Ganser A, Zeidler C, Kreipe HH, Burkhardt J, Grosschedl R, Welte K. Interactions among HCLS1, HAX1 and LEF-1 proteins are essential for G-CSF-triggered granulopoiesis. Nat Med. 2012 Sep 23;18(10):1550-9.

 

Rhein M, Schwarzer S, Yang M, Kaever V, Brugman M, Meyer J, Ganser A, Baum C, Li Z. Leukemias induced by altered TRK-signaling are sensitive to mTOR inhibitors in preclinical models Annals of Hematology 2011;90:283-292

 

Li Z*, Beutel G, Rhein M, Meyer J, Koenecke C, Neumann T, Yang M, Krauter J, von Neuhoff N, Heuser M, Diedrich H, Göhring G, Wilkens L, Schlegelberger B, Ganser A, Baum C*. (*co-corresponding author) Neurotrophin receptors and ligands promote leukemogenesis. Blood 2009;113(9):2028-37.

 

Meyer J, Rhein M, Schiedlmeier B, Kustikova O, Rudolph C, Kamino K, Neumann T, Yang M, Wahlers A, Fehse B, Schlegelberger B, Reuther GW, Ganser A, Baum C, Li Z. Remarkable leukemogenic potency and quality of a constitutively active neurotrophin receptor, DTrkA. Leukemia 2007; 21:2171-2180

 

Beutel G, Meyer J, Ma L, Yin S, Eder M, von Neuhoff N, Wilkens L, Wie J, Hertenstein B, Heil G, Schlegelberger B, Ganser A, Li Z*, Baum C. (*corresponding author) Expression of the p75 neurotrophin receptor in acute leukaemia. British Journal of Haematology 2005; 131:67–70

 

Kustikova O, Fehse B, Modlich U, Yang M, Düllmann J, Kamino K, von Neuhoff N, Schlegelberger B, Li Z*, Baum C*. (*co-corresponding author) Clonal dominance of hematopoietic stem cells triggered by retroviral gene marking. Science 2005; 308:1171-1174

 

Schiedlmeier B, Klump H, Will E, Arman-Kalcek G, Li Z, Wang Z, Friel J, Baum C, Ostertag W. High level ectopic HOXB4 expression confers a profound in vivo competitive growth advantage to human cord blood CD34+ cells, but impairs lymphomyeloid differentiation. Blood 2003;101:1759-68.

 

Baum C, Duellmann J, Li Z, Fehse B, Meyer J, Williams DA, C von Kalle. Side effects of retroviral gene transfer into hematopoietic stem cells. Blood 2003; 101:2099-2113.

 

Li Z, Schwieger M, Lange C, Kraunus J, Sun H, van den Akker E, Modlich U, Serinsöz E, Will E, von Laer D, Stocking C, Fehse B, Schiedlmeier B, Baum C. Predictable and efficient retroviral gene transfer into murine bone marrow repopulating cells using a defined vector dose. Experimental Hematology 2003; 31:1206-1214

 

Li Z, Düllmann J, Schiedlmeier B, Schmidt M, von Kalle C, Meyer J, Forster M, Stocking C, Ostertag W, Wahlers A, Frank O, Kuehlcke K, Eckert HG, Fehse B, Baum C. Murine leukemia induced by retroviral gene marking. Science 2002; 296:497

 

Li Z, Fehse B, Schieldmeier B, Düllmann J, Frank O, Zander AR, Ostertag W, Baum C. Persisting multilineage transgene expression in the clonal progeny of a hematopoietic stem cell. Leukemia 2002;16:1655-63

 

Li Z*, Yin S, Xie S, Ma L, Nie D, Xsu L. (*corresponding author) Treatment of severe aplastic anemia using high-dose Cyclophosphamide alone in China. Haematologica 2000;85(E-letters):06 (http://www.haematologica.it/e-letter)

 

Li ZX, Schade UM, Fehse B, Stockschläder M, Uhde A, Koch S, Goller B, Rüger R, Fehse N, Zander AR. High-efficient retroviral vector-mediated gene transfer into human T lymphocytes. Adv Exp Med Biol 1998; 451:375-378


Anschrift
Hämatologie, Hämostaseologie,
Onkologie und Stammzelltransplantation
Medizinische Hochschule Hannover
Carl-Neuberg-Str. 1
30625 Hannover
Tel.:(+49) 511 532-3020
Fax:(+49) 511 532-8041

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