research
Research Interests
The ‘signal transducer and activator of transcription’ STAT5 is an essential mediator of cytokine signaling. STAT5 deregulation, especially its constitutive activation, directly contributes to tumorigenesis and is associated with a variety of cancers (leukemia, mammary carcinoma, melanoma). Our research focuses on the characterization of the molecular mechanisms of transcriptional regulation by STAT5 in normal and cancer cells.
Our work includes:
- the identification of novel STAT5 target genes encoding proteins or ncRNAs, and the study of their regulation at the chromatin level
- the characterization of epigenetic regulation by STAT5, and its implication in STAT5-mediated cellular transformation
Our ultimate goal is the identification of relevant therapeutic targets for intervention in STAT5-associated cancers.
Methods
- Chromatin and epigenetic studies : Chromatin Immunoprecipitation (ChIP,
ChIP-on-chip), Chromatin remodeling (CHART-PCR)
- Gene expression studies : Quantitative RT-PCR, microarray-based expression
profiling, luciferase reporter assays, RNA interference
- Standard molecular and cellular biology methods (DNA, RNA and protein
manipulation, cell culture)
CV
Curriculum Vitae
| Since 09/2010 | DFG-funded independent Group Leader at the Institute for Immunology, University of Regensburg, Germany |
| 2009 | Habilitation in “Cell Biology”, Faculty of Natural Sciences (NWF III), University of Regensburg, Germany |
| 2004-2010 | Project Leader at the Institute for Molecular and Cellular Anatomy, University of Regensburg, Germany |
| 2000-2004 | Senior Postdoc/Principal Investigator in the Dpt of Oncology and Discovery Research, DNAX Research Inc. (presently Merck Research Laboratories), Palo Alto, USA |
| 1995-1999 | Postdoc in the Dpt of Developmental Biology, Stanford University School of Medicine, USA (Prof. David S. Hogness) |
| 1990-1994 | PhD in Molecular and Cellular Biology, Ecole Normale Supérieure de Lyon/University of Lyon, France (Dr. Jacques Samarut) |
| 1985-1990 | Graduation in Biology, University of Lyon, France |
publications
Recent publications
| Rascle, A.*, Neumann, T., Raschta, A-S., Neumann, A., Heining, E., Kastner, J., and Witzgall, R. (2009). The LIM-Homeodomain transcription factor LMX1B regulates expression of NF-kappaB target genes. Exp. Cell Res. 315, 76-96. |
| Basham, B., Sathe, M., Grein, J., McClanahan, T., d’Andrea, A., Lees, E., and Rascle, A.* (2008). In vivo Identification of Novel STAT5 Target Genes. Nucleic Acids Res. 36, 3802-18. |
| Suleiman, H., Heudobler, D., Raschta, A-S., Zhao, Y., Zhao, Q., Hertting, I., Vitzthum, H., Moeller, M.J., Holzman, L.B., Rachel, R., Johnson, R., Westphal, H., Rascle, A., and Witzgall, R. (2007). The podocyte-specific inactivation of Lmx1b, Ldb1 and E2a yields new insight into a transcriptional network in podocytes. Dev. Biol. 304, 701-712. |
| Burrows, J.F., McGrattan, M., Rascle, A., Humbert, M., Baek K-H., and Johnston, J.A. (2004). DUB-3, a cytokine-inducible deubiquitinating enzyme that blocks proliferation. J. Biol. Chem. 279, 13993-14000. |
| Rascle, A.*, Johnston, J.A., and Amati, B. (2003). A deacetylase activity is required for recruitment of the basal transcription machinery and transactivation by STAT5. Mol. Cell. Biol. 23, 4162-4173. |
| Rascle, A.*, and Lees, E. (2003). Chromatin acetylation and remodeling at the Cis promoter during STAT5-induced transcription. Nucleic Acids Res. 31, 6882-6890. |
| Rascle, A.*, Stowers R.S., Garza D., Lepesant J.A., and Hogness D.S. (2003). L63, the Drosophila PFTAIRE, interacts with two novel proteins unrelated to cyclins. Mech. Dev. 120, 617-628. |
| Migone, T-S.§, Humbert, M.§, Rascle, A.§, Sanden, D., D'Andrea, A., and Johnston, J.A. (2001). The deubiquitinating enzyme Dub-2 prolongs cytokine-induced STAT activation and suppresses apoptosis following cytokine withdrawal. Blood 98, 1935-1941. § equal contribution |
| Rascle, A., Ferrand, N., Gandrillon, O., and Samarut, J. (1996). Myb-Ets fusion oncoprotein inhibits T3R/c-ErbA and RAR functions: a novel mechanism of action for leukemogenic transformation by E26 avian retrovirus. Mol. Cell. Biol. 16, 6338-6351. |
| Rascle, A., Ghysdael, J., and Samarut, J. (1994). c-ErbA, but not v-ErbA, interferes with a putative erythroid repressor for binding to the carbonic anhydrase II promoter. Oncogene 9, 2853-2867. |
* corresponding author
