Research Interests

This laboratory investigates how signal transduction pathways orchestrate the complex patterns of gene expression that are required for cell function and proper organism development.  We perform biochemical, genetic and genomic experiments in mammalian cell culture systems and in the fruitfly Drosophila melanogaster aimed at understanding the function of transcription factors, kinases and other signaling components. In addition, we are dissecting the genetic programs that are regulated by signal transduction cascades and inducible transcription factors. 

Projects and Goals

Transcription factor function

The transcription factors Jun and Fos serve as our paradigms to investigate how eukaryotic genes are turned on or off. Employing proteomic technologies, biochemistry and tissue culture techniques we have mapped and functionally characterized relevant molecular interactions that confer signal dependent regulation of gene transcription.

Signaling specificity

Cells in an organism are confronted a complex stream of information, originating from their sister cells or from the external environment. This information has to be perceived and appropriately interpreted for the cell to act in a biological appropriate manner. Failure of signal relay can have detrimental consequences for the health or survival of the organism. We study how transcription factors respond specifically to various upstream signals.

The genetic basis of cell growth and proliferation.

We employed SAGE as a method for genome wide transcription profiling during Drosophila development to identify gene expression programs associated with cell proliferation. We are currently studying the factors and mechanisms that confer this genetic program.

The JNK pathway in Drosophila: Morphogenesis and Stress Response.

The JNK MAP kinase pathway regulates changes of cell and tissue shape during development and also elicits a stress response program. We are dissecting the upstream and downstream components of these two modes of JNK action using the power of Drosophila genetics. These studies should reveal general principles of this important conserved signaling system.

1. Musti, A.M., Treier, M. & Bohmann, D. (1997) Reduced ubiquitin-dependent degradation of c-Jun after phosphorylation by MAP kinases, Science, 275, 400-402.

2. Kockel, L., Zeitlinger, J., Staszewski, L., Mlodzik, M. & Bohmann, D. (1997) Jun in Drosophila development: Redundant and non-redundant functions, and regulation by two MAPK signal transduction pathways. Genes & Development, 11, 1748-1758

3. Zeitlinger, J., Kockel, L., Peverali, F.A., Jackson, D.B., Mlodzik, M. & Bohmann, D. (1997) Defective dorsal closure and loss of epidermal decapentaplegic expression in Drosophila fos mutants. EMBO J., 16, 7393-7401.

4. LeppŠ, S., Saffrich, R., Ansorge, W. & Bohmann, D. (1998) Differential regulation of c-Jun by ERK and JNK during PC12 cell differentiation. EMBO J., 17, 4404-4413.

5. Zeitlinger, J. & Bohmann, D. (1999) Thorax closure in Drosophila: The role of Fos and the JNK pathway. Development, 126, 3947-3956.

6. Kockel L., Homsy, J.G. & Bohmann, D. (2001) Drosophila AP-1: lessons from an invertebrate. Oncogene, 20, 2347-2364.

7. Leppä, S., Eriksson, M., Saffrich, R., Ansorge, W. & Bohmann, D. (2001) Complex Functions of AP-1 transcription factors in differentiation and survival of PC12 cells. Mol. Cell Biol., 21, 4369-4378.

8. Ciapponi, L. Jackson, D.B., Mlodzik, M., Bohmann, D. (2001) Drosophila Fos mediates ERK and JNK signals via distinct phosphorylation sites. Genes & Development, 15, 1540-1553.

9. Jasper, H., Benes, V., Schwager, C., Sauer, S., Clauder-Münster, S., Ansorge, W., Bohmann, D. (2001) The genomic response of the Drosophila embryo to JNK signaling. Developmental Cell, 1, 579-586.

10. Westermarck, J., Weiss, C., Saffrich, R., Kast, J., Musti, A.M., Wessely, M., Ansorge, W., Bohmann, D. (2002) The DEAD/H-box RNA helicase RHII/Gu is a co-factor for c-Jun activated transcription. EMBO J., 21, 451-460.

11. Jasper, H., Benes, V., Atzberger, A., Sauer, S., Ansorge, W., Bohmann, D. (2002) Developmental Cell, 2, 511-521.

12. Jasper, H. & Bohmann, D. (2002) Drosophila innate immunity: a genomic view of pathogen defense. Molecular Cell, 10, 967-969.

13. Weiss, C., Schneider, S., Wagner, E.F., Zhang, X., Seto, E. & Bohmann, D. (2003) JNK phosphorylation relieves HDAC3 dependent suppression of c-Jun’s transcriptional activity. EMBO J., 22, 3686-3695

14. Wang, M.C., Bohmann, D. & Jasper, H. (2003) JNK signaling confers tolerance to oxidative stress and extends lifespan in Drosophila. Developmental Cell, 5, 811-816.

15. Portman, D.S. & Bohmann, D. (2004) Towards the Computable Transcriptome. Molecular Cell, 14, 693-694.

16. Wang, M.C., Bohmann, D. & Jasper, H. (2005) JNK extends lifespan and limits growth by antagonizing cellular and organism-wide responses to Insulin signaling Cell, 121, 115-125.

17. Hyun, J., Jasper, H. & Bohmann, D. (2005) DREF is required for efficient growth and cell cycle progression in Drosophila imaginal discs, Mol. Cell Biol., 25, 5590-5598.

18. Uhlirova, M. Jasper, H. & Bohmann, D. (2005) Non-Cell autonomous tissue overgrowth induced by JNK/Ras cooperation in a Drosophila tumor model. Proc. Natl. Acad. Sci. USA, 102, 13123-13128.