Wolfgang M. J. Obermann, Ph.D.
Associate Professor

Wolfgang M. J. Obermann, Ph.D.

Education

• Diplom Biochemistry, University of Tübingen and Max-Planck-Institute for Developmental Biology, Tübingen, 1992
• Ph. D. Biochemistry, University of Tübingen and Max-Planck-Institute for Biophysical Chemistry, Göttingen, 1996
• Postdoc, Memorial Sloan Kettering Cancer Center, New York and Max-Planck-Institute for Biochemistry, Martinsried, 1997-2000
• Habilitation, Genetics, University of Bonn, 2004

About the Lab

The molecular chaperone Hsp90 (Heat shock protein 90) works in an ATP dependent manner to regulate the activity of a limited subset of medically relevant signalling proteins such as steroid hormone receptors and several kinases. In order to control the conformation of its client proteins, Hsp90 cooperates  with a variety of cochaperones like Aha1, Hop, p23, p50, Tpr2 and others. The dependence of oncogenic kinases on Hsp90 and its vulnerability to drugs have made Hsp90 a promising target for cancer therapy. Our new findings show that in addition to this role, Hsp90 plays a role in the regulation of intracellular vesicle transport and may therefore have the potential to affect synaptic transmission in the nervous system. Moreover we are interested to understand the interplay between Hsp90 and androgen receptor, a specific client protein that undergoes polyglutamine dependent aggregation leading to spinal and bulbar muscular atrophy or Kennedy’s disease, a neuromuscular disorder. Finally, we are using yeast and mouse models to understand the physiological role of the Hsp90 chaperone system.

Selected Publications

Cintrón Moffatt, N.S., E. Bruinsma, C. Uhl, W.M.J.  Obermann, and D. Toft. 2008. The role of the co-chaperone Tpr2 in Hsp90 chaperoning. Biochemistry, in press.

Lotz, G.P., A. Brychzy, S. Heinz, and W.M.J. Obermann. 2008. A novel Hsp90 chaperone complex regulates intracelluar vesicle transport. J. Cell Sci. 121: 717-723.

Hawle, P., M. Siepmann, A. Harst, M. Siderius,  H.P. Reusch, and W.M.J. Obermann. 2006. The middle domain of Hsp90 acts as a discriminator between different types of client proteins. Mol. Cell. Biol. 26: 8385-8395.

Harst, A., H. Lin, and W.M.J. Obermann. 2005. Aha1 competes with Hop, p50 and p23 for binding to the molecular chaperone Hsp90 and contributes to kinase and hormone receptor activation. Biochem. J. 387: 789-796.

Brychzy, A., T. Rein, K.F. Winklhofer, F.U. Hartl, J.C. Young, and W.M.J. Obermann 2003. Cofactor Tpr2 combines two TPR domains and a J domain to regulate the Hsp70/Hsp90 chaperone system. EMBO J. 22: 3613-3623.

Lotz, G.P., H. Lin, A. Harst, and W.M.J. Obermann. 2003. Aha1 binds to the middle domain of Hsp90, contributes to client protein activation and stimulates the ATPase activity of the molecular chaperone. J. Biol. Chem. 278: 17228-17235.