Dr. Frank Rosenbauer
Max-Delbrück-Center for Molecular Medicine (MDC)
Robert-Rössle-Str. 10
13125 Berlin, Germany
House: 31.1, Room 4018
Phone: +49 30 9406 2544
f.rosenbauer [at] mdc-berlin.de
Cancer, Stem Cells, and Transcription Factors
In recent years, great progress has been made in elucidating the stem and progenitor cell hierarchy of the hematopoietic system. The step-wise adoption of a cellular lineage identity during hematopoietic differentiation is preceded by the ordered reorganization of the chromatin, which is mediated by both genetic and epigenetic factors. Transcription factors are key determinants in the orchestration of cellular identity and differentiation fates through expression modulation of specific target gene subsets. Most transcription factors show narrow celllineage-and stage-restricted expression patterns, indicating the requirement for tight regulation of their activities. Moreover, if dysregulated or mutated, these transcription factors cause the differentiation block observed in many leukaemias. Using mouse genetics as well as biochemical approaches, our research group is particularly interested in the activities and transcriptional regulation of main hematopoietic transcription factors, such as PU.1, and in their functional interplay with epigenetic chromatin modifiers.
Publications
Broeske AM; Vockentanz L; Kharazi S; Huska MR; Mancini E; Scheller M; Kuhl C; Enns A; Prinz M; Jaenisch R; Nerlov C; Leutz A; Andrade-Navarro MA; Jacobsen SE; Rosenbauer F: DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction. Nature Genetics : (2009-10-04)
Ebralidze AK; Guibal FC; Steidl U; Zhang P; Lee S; Bartholdy B; Jorda MA; Petkova V; Rosenbauer F; Huang G; Dayaram T; Klupp J; O'Brien KB; Will B; Hoogenkamp M; Borden KL; Bonifer C; Tenen DG: PU.1 expression is modulated by the balance of functional sense and antisense RNAs regulated by a shared cis-regulatory element. Genes & Development 22 (15): 2085-2092 (2008-08-01)
Feinberg MW; Wara AK; Cao Z; Lebedeva MA; Rosenbauer F; Iwasaki H; Hirai H; Katz JP; Haspel R; Gray S; Akashi K; Segre J; Kaestner KH; Tenen DG; Jain MK: The Kruppel-like factor KLF4 is a critical regulator of monocyte differentiation. EMBO Journal 26 (18): 4138-48 (2007-09-19)
Steidl U; Steidl C; Ebralidze A; Chapuy B; Han HJ; Will B; Rosenbauer F; Becker A; Wagner K; Koschmieder S; Kobayashi S; Costa DB; Schulz T; OBrien KB; Verhaak RG; Delwel R; Haase D; Truemper L; Krauter J; Kohwi-Shigematsu T; Griesinger F; Tenen DG: A distal single nucleotide polymorphism alters long-range regulation of the PU.1 gene in acute myeloid leukemia. Journal of Clinical Investigation 117 (9): 2611-2620 (2007-09)
Rosenbauer F; Tenen DG: Transcription factors in myeloid development: balancing differentiation with transformation. Nature Reviews Immunology 7 (2): 105-117 (2007-02)
Steidl U; Rosenbauer F; Verhaak RG; Gu X; Ebralidze A; Otu HH; Klippel S; Steidl C; Bruns I; Costa DB; Wagner K; Aivado M; Kobbe G; Valk PJ; Passegue E; Libermann TA; Delwel R; Tenen DG: Essential role of Jun family transcription factors in PU.1 knockdown-induced leukemic stem cells. Nature Genetics 38: 1269-1277 (2006-10-15)
Wagner K; Zhang P; Rosenbauer F; Drescher B; Kobayashi S; Radomska HS; Kutok JL; Gilliland DG; Krauter J; Tenen DG: Absence of the transcription factor CCAAT enhancer binding protein alpha results in loss of myeloid identity in bcr/abl-induced malignancy. Proceedings of the National Academy of Sciences of the United States of America 103: 6338-6343 (2006-04-18)
Scheller M; Huelsken J; Rosenbauer F; Taketo MM; Birchmeier W; Tenen DG; Leutz A: Hematopoietic stem cell and multilineage defects generated by constitutive beta-catenin activation. Nature Immunology 7 (10): 1037-1047 (2006-10)
Rosenbauer F; Owens BM; Yu L; Tumang JR; Steidl U; Kutok JL; Clayton LK; Wagner K; Scheller M; Iwasaki H; Liu C; Hackanson B; Akashi K; Leutz A; Rothstein TL; Plass C; Tenen DG: Lymphoid cell growth and transformation are suppressed by a key regulatory element of the gene encoding PU.1. Nature Genetics 38 (1): 27-37 (2006-01)