Regulation in Cellular Signal Transduction

Cells respond to a large variety of signals using only a limited set of signaling modules which are organized in complex networks. The activity of these signaling switches is spatially and temporally regulated, and this regulation governs normal development and cellular homeostasis. Consequently, uncontrolled activation is a hallmark of many diseases such as cancer. It is therefore not surprising that the cell has intricate regulatory mechanisms in place to control signal transduction.

Dr. Sondermann's lab is interested in deciphering the basic regulatory principles in signal transduction networks on a molecular level, focusing on growth factor receptor signaling. In particular, they study the role of scaffolding proteins and other regulators signal transduction in this pathway, using a combination of X-ray crystallography, biophysical and cellular approaches. Scaffolds, which serve as docking hubs for the signaling switches, provide specificity and higher-order control in signaling reactions. Understanding the architecture, mode of action and regulation of these processes will elucidate how cells respond to various inputs producing distinct outputs by using a limited set of molecules.

• Freedman, T.S.*, Sondermann, H.* , Friedland, G., Kortemme, T., Bar-Sagi, D., Marqusee, S., and Kuriyan, J. (2006). A Ras-induced conformational switch in the Ras activator Son of sevenless. Proc Natl Acad Sci USA 103(45): 16692-16697.
  (*These authors contributed equally to this work.)
• Boykevisch, S., Zhao, C., Sondermann, H. , Philippidou, P., Halegoua, S., Kuriyan, J., and Bar-Sagi, D. (2006). Regulation of Ras signaling dynamics by Sos-mediated positive feedback. Current Biology 16(21): 2173-2179.
• Pirruccello, M., Sondermann, H., Pelton, J.G., Pellicena, P., Hoelz, A., Chernoff, J., Wemmer, D.E., and Kuriyan, J. (2006). A dimeric kinase assembly underlying autophosphorylation in the p21 Activated Kinases. J Mol Biol 361: 312-326.
• Sondermann, H. , Nagar, B., Bar-Sagi, D., and Kuriyan, J. (2005). Computational docking and X-ray scattering predict a membrane-interacting role for the histone domain of the Ras-activator Son of Sevenless. Proc Natl Acad Sci USA 102(46):16632-16637.
• Sondermann, H. , and Kuriyan, J. (2005). C2 can do it, too. Cell 121:158-160 (Preview).
• Mao, X., Ren, Z., Parker, G.N., Sondermann, H. , Pastorello, M.A., Wang, W., McMurray, J.S., Demeler, B., Darnell, J.E.Jr., and Chen, X. (2005). Structural bases of unphosphorylated STAT1 association and receptor binding. Molecular Cell 17(6):761-771.
• Sondermann, H. *, Zhao, C.*, and Bar-Sagi, D. (2005). Analysis of Ras:RasGEF Interactions by Phage Display and Static Multi Angle Light Scattering. Methods 37(2):197-202) .
• (*These authors contributed equally to this work.)
• Sondermann, H. *, Soisson, S.M.*, Boykevisch, S., Yang, S.-S., Bar-Sagi, D., and Kuriyan, J. (2004). Structural analysis of autoinhibition in the Ras activator Son of Sevenless. Cell 119(3):393-405.
• (*These authors contributed equally to this work.)
• Sondermann, H. , Soisson, S.M., Bar-Sagi, D., and Kuriyan, J. (2003). Tandem histone folds in the structure of the N-terminal segment of the Ras activator Son of Sevenless. Structure 11(12):1583-1593.
• Harkiolaki, M., Lewitzky, M., Jones, E.Y., Bourette, R., Mouchiroud, G., Sondermann, H. , Moarefi, I. and Feller, S.M. (2003). Structural basis for SH3 domain-mediated high-affinity binding between Mona/Gads and SLP-76. EMBO J 22:2571-2582.
• Margarit, S.M., Sondermann, H. , Hall, B.E., Nagar, B., Hoelz, A., Pirruccello, M., Bar-Sagi, D. and Kuriyan, J. (2003). Structural evidence for feedback activation by Ras.GTP of the Ras-specific nucleotide exchange factor SOS. Cell 112(5):685-695.
• Sondermann, H. , Ho, A.K., Listenberger, L.L., Siegers, K., Moarefi, I., Wente, S.R., Hartl, F.U. and Young, J.C. (2002). Prediction of novel Bag-1 homologs based on structure/function analysis identifies Snl1p as an Hsp70 co-chaperone in S. cerevisiae . J Biol Chem 277(36):33220-33227.
• El Mourabit, H., Poinat, P., Koster, J., Sondermann, H. , Wixler, V., Wegener, E., Laplantine, E., Geerts, D., Georges-Labouesse, E., Sonnenberg, A. and Aumailley, M. (2002). The PDZ domain of TIP-2/GIPC interacts with the C-terminus of the integrin a 5 and a 6 subunits. Matrix Biol 21(2):207-214.
• Sondermann, H. , Scheufler, C., Schneider, C., Hohfeld, J., Hartl, F.U. and Moarefi, I. (2001). Structure of a Bag/Hsc70 complex: convergent functional evolution of Hsp70 nucleotide exchange factors. Science 291(5508):1553-7.
• Sondermann, H. , Becker, T., Mayhew, M., Wieland, F. and Hartl, F.U. (2000). Characterization of a receptor for heat shock protein 70 on macrophages and monocytes. Biol Chem 381(12):1165-74.
• Sondermann, H. , Dogic, D., Pesch, M. and Aumailley, M. (1999). Targeting of cytoskeletal linker proteins to focal adhesion complexes is reduced in fibroblasts adhering to laminin-1 when compared to fibronectin. Cell Adhes Commun 7(1):43-56.
• Obermann, W.M., Sondermann, H. , Russo, A.A., Pavletich, N.P. and Hartl, F.U. (1998). In vivo function of Hsp90 is dependent on ATP binding and ATP hydrolysis. J Cell Biol 143(4):901-10.

• Veterinary Library Committee, February 2006 - present
• Seminar Coordinator at the Department of Molecular Medicine, June 2006 - present
• Executive Committee member, Graduate Field of Pharmacology, September 2006 - present
• Member of  German Society for Biochemistry and Molecular Biology (GBM)
• Member of  Biophysical Society
• Member of  The Protein Society

• Robert N. Noyce Assistant Professor in Life Science and Technology, June 2006 - present

• Leukemia & Lymphoma Society Fellowship (Career Development Program), he Leukemia & Lymphoma Society, USA, July 2002 - July 2005

• Young Investigator Research Award, Max-Planck-Institute of Biochemistry, Germany, 2002