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Molecular Hematopoiesis

Contact/Address

 

Principle Investigator:

Florian Kuchenbauer MD, PhD

Department of Internal Medicine III /  Institute of Experimental Cancer Research

University Hospital of Ulm

Albert-Einstein-Allee 23

89081 Ulm

Deutschland

 

E-Mail: florian.kuchenbauer[at]uni-ulm.de

Phone:

Phone (Lab):

FAX:

0049-731-500-45991

0049-731-500-45848

0049-731-500-45525

Postdoctoral fellow:

 

 


Technicians:

Nicole Pochert, MSc

Christina Miller

Angelika Vollmer

 

 

nicole.hunger[at]uni-ulm.de

 

angelika.vollmer[at]uni-ulm.de

PhD students:

Kathrin Krowiorz, MSc

Edith Schneider, MSc

Sarah Grasedieck, MSc

Nadine Sperb, BSc

Dr. rer. nat. Arefeh Rouhi

kathrin.krowiorz[at]uni-ulm.de

edith.schneider[at]uni-ulm.de

 

 

arefeh.rouhi(at)uni-ulm.de


 

Research Fields

 

A) Mechanisms of Lineage Fate Decisions in normal and aberrant hematopoiesis

What determines lineage fate decisions of hematopoietic stem cells? We are interested in elucidating the molecular mechanisms and identifying novel genes involved in this process. Furthermore, we are investigating possibilities of reverting the block of differentiation in leukemic stem cells as potential therapeutic approaches.

Figure “Lineage fate decisions through miRNAs”

 

Relevant Publications

Heuser M, Yun H, Berg T, Yung E, Argiropoulos B, Kuchenbauer F, Park G, Hamwi I, Palmqvist L, Lai CK, Leung M, Lin G, Chaturvedi A, Thakur BK, Iwasaki M, Bilenky M, Thiessen N, Robertson G, Hirst M, Kent D, Wilson NK, Göttgens B, Eaves C, Cleary ML, Marra M, Ganser A, Humphries RK. Cell of origin in AML: susceptibility to MN1-induced transformation is regulated by the MEIS1/AbdB-like HOX protein complex. Cancer Cell. 2011 Jul 12;20(1):39-52.

Kuchenbauer F, Mah SM, Heuser M, McPherson A, Ruschmann J, Rouhi A, Berg T, Bullinger L, Argiropoulos B, Morin RD, Lai D, Starczynowski DT, Karsan A, Eaves CJ, Watahiki A, Wang Y, Aparicio SA, Ganser A, Krauter J, Döhner H, Döhner K, Marra MA, Camargo FD, Palmqvist L, Buske C, Humphries RK. Comprehensive analysis of mammalian miRNA* species and their role in myeloid cells. Blood. 2011 Sep 22;118(12):3350-8.

 

B) Functional characterization of genetic driver lesions in acute myeloid leukemia (AML)

Based on established in vitro and in vivo AML progression models, we are currently testing potential genetic drivers of leukemogenesis. This includes extensive in vitro screens as well as in vivo testing using murine models. Identification of novel leukemic drivers will lead to a better understanding how leukemias arise and eventually result in new druggable targets.

 

Figure “Identification of novel driver of leukemogenesis”

 

Relevant Publications

Gasparetto M, Sekulovic S, Brocker C, Tang P, Zakaryan A, Xiang P, Kuchenbauer F, Wen M, Katayoon K, Witty MF, Rosten P, Chen Y, Imren S, Duester G, Thompson DC, Humphries RK, Vasiliou V, Smith C. Aldehyde dehydrogenases are regulators of hematopoietic stem cell numbers and B-cell development. Exp Hematol. 2011 Dec 20.

Heuser M, Berg T, Kuchenbauer F, Lai CK, Park G, Fung S, Lin G, Leung M, Krauter J, Ganser A, Humphries RK. Functional role of BAALC in leukemogenesis.Leukemia. 2011 Aug 26.

Argiropoulos B, Yung E, Xiang P, Lo CY, Kuchenbauer F, Palmqvist L, Reindl C, Heuser M, Sekulovic S, Rosten P, Muranyi A, Goh SL, Featherstone M, Humphries RK.Linkage of the potent leukemogenic activity of Meis1 to cell cycle entry and transcriptional regulation of cyclin D3. Blood. 2010 May 20;115(20):4071-82.

Heuser M, Argiropoulos B, Kuchenbauer F, Yung E, Piper J, Fung S, Schlenk RF, Dohner K, Hinrichsen T, Rudolph C, Schambach A, Baum C, Schlegelberger B, Dohner H, Ganser A, Humphries RK. MN1 overexpression induces acute myeloid leukemia in mice and predicts ATRA resistance in patients with AML. Blood. 2007 Sep 1;110(5):1639-47.

Kuchenbauer F, Schnittger S, Look T, Gilliland G, Tenen D, Haferlach T, Hiddemann W, Buske C, Schoch C. Identification of additional cytogenetic and molecular genetic abnormalities in acute myeloid leukaemia with t(8;21)/AML1-ETO. Br J Haematol. 2006 Sep;134(6):616-9.

 

C) The role of non-coding RNAs in acute myeloid leukemia

Based on a recent screen, miRNAs will be tested for their potential to manipulate hematopoietic as well as leukemic stem cells. Furthermore, we study upstream mechanisms regulating miRNA expression, such as epigenetic modifications. Based on our findings, we are planning to test miRNAs as therapeutic agents.

 

Figure “Canonical processing of miRNAs”

 

Relevant Publications

Petriv OI*, Kuchenbauer F*, Delaney AD, Lecault V, White A, Kent D, Marmolejo L, Heuser M, Berg T, Copley M, Ruschmann J, Sekulovic S, Benz C, Kuroda E, Ho V, Antignano F, Halim T, Giambra V, Krystal G, Takei CJ, Weng AP, Piret J, Eaves C, Marra MA, Humphries RK, Hansen CL. *authors contributed equally. Comprehensive microRNA expression profiling of the hematopoietic hierarchy. Proc Natl Acad Sci USA. 2010 Aug 31;107(35):15443.

Petriv OI, Hansen CL, Humphries RK, Kuchenbauer F. Probing the complexity of miRNA expression across hematopoiesis. Cell Cycle. 2011 Jan 1;10(1):2-3.

Starczynowski DT, Morin R, McPherson A, Lam J, Chari R, Wegrzyn J, Kuchenbauer F, Hirst M, Tohyama K, Humphries RK, Lam WL, Marra M, Karsan A. Genome-wide identification of human microRNAs located in leukemia-associated genomic alterations. Blood. 2011 Jan 13;117(2):595-607.

Starczynowski DT, Kuchenbauer F, Wegrzyn J, Rouhi A, Petriv O, Hansen CL, Humphries RK, Karsan A. MicroRNA-146a disrupts hematopoietic differentiation and survival. Exp Hematol. 2011 Feb;39(2):167-178.e4.

Starczynowski DT, Kuchenbauer F, Argiropoulos B, Sung S, Morin R, Muranyi A, Hirst M, Hogge D, Marra M, Wells R, Buckstein R, Lam W, Humphries RK, Karsan A. Identification of miR-145 and miR-146a as mediators of the 5q- syndrome phenotype, Nat Med. 2010 Jan;16(1):49-58.

Kuchenbauer F*, Morin RD*, Argiropoulos B, Petriv OI, Griffith M, Heuser M, Yung E, Piper J, Delaney A, Prabhu A, Zhao Y, McDonald H, Zeng T, Hirst M, Hansen CL, Marra MA, Humphries RK. In depth characterization of the microRNA transcriptome in a leukemia progression model. Genome Res. 2008 Nov;18(11):1787-97. *authors contributed equally.

Kuchenbauer F. MicroRNAs, epigenetics and leukemias. Epigenomics, 2009 Dec; 1(2):219-222.

Rouhi A, Mager DL, Humphries RK, Kuchenbauer F. MiRNAs, epigenetics, and cancer. Mamm Genome. 2008 Aug;19(7-8):517-25.

 

D) Identification of microRNAs as novel biomarkers

Treatment of medical conditions is in many cases symptom-oriented. In the case of malignant diseases, tumor markers, usually more or less specific circulating proteins, are used to monitor disease activity. However, for the majority of diseases neither markers for disease activity nor for therapy response are available. Therefore, we explore the potential of miRNAs in body fluids as biomarkers for malignant and non-malignant diseases. Furthermore, we are interested in developing diagnostic tests for rapid detection of miRNAs.

 

Relevant Publications

Grasedieck S, Schöler N, Bommer M, Niess JH, Tumani H, Rouhi A, Bloehdorn J, Liebisch P, Mertens D, Döhner H, Buske C, Langer C, Kuchenbauer F. Impact of serum storage conditions on microRNA stability. Leukemia. 2012 Apr 16.

Schöler N, Langer C, Kuchenbauer F. Circulating microRNAs as biomarkers - True Blood? Genome Med. 2011 Nov 23;3(11):72.

Schöler N, Langer C, Döhner H, Buske C, Kuchenbauer F. Serum miRNAs as a novel class of biomarkers: a comprehensive review of the literature. Exp Hematol. 2010 Dec;38(12):1126-30. Review.

Grants

  • Wilhelm-Sander-Stiftung
  • Deutsche Forschungsgemeinschaft (DFG, SFB 1074)
  • Max-Eder Nachwuchsgruppe (Deutsche Krebshilfe)
  • Deutsche Krebshilfe

Techniques

  • common molecular biology
  • murine models (in vitro / in vivo)

External collaborations

  • Terry Fox Laboratory (Vancouver, Canada)
  • University of British Columbia (Vancouver, Canada)
  • MHH (Hannover, Germany)
  • HSR-TIGET (Milano, Italy)

Forschungsbereiche

Molecular Genetics of Myeloid Leukemia
Prof. Dr. Konstanze Döhner / Prof. Dr. Lars Bullinger

Molecular Genetics of Myeloproliferative Disorders
Dr. Frank Stegelmann / Prof. Dr. Konstanze Döhner

Molecular Pathogenesis and Progression of Lymphoproliferative Disorders
Prof. Dr. Stephan Stilgenbauer

Mechanisms of Leukemogenesis
PD Dr. Daniel Mertens

Molecular Pathogenesis and Prognostic Markers in Monoclonal Gammopathies
PD Dr. Christian Langer

Tumor Immunology Group (TIG)
Prof. Dr. Jochen Greiner

Haemostaseology
PD Dr. Christian Langer
 

Molecular Hematopoiesis
Dr. Dr. Florian Kuchenbauer

 

Emmy Noether Research Group

Dr. Jan Krönke

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