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Scripps Research Joint Appointments

Faculty, Kellogg School of Science and Technology

Research Focus

My broad research interest are the signal transduction mechanisms governing development and function of the immune system. We aim to identify novel molecular mechanisms through which the immune system protects us from pathogens, and to elucidate molecular defects which cause autoimmune diseases, immunodeficiencies, leukemias and lymphomas. By improving our mechanistic understanding of these important conditions, we hope to identify and validate novel targets for improved therapies.
Through functional genomics and systems biology, we have identified several novel mechanisms that we are now studying in detail, using multidisciplinary and organism-wide "systems" approaches. In one main project, we are investigating the roles of soluble inositol phosphates as important but little understood novel messengers in lymphocyte signaling and development. A current focus is inositol tetrakisphosphate (IP4), which we recently identified as a soluble regulator of phosphoinositide 3-kinase (PI3K) function, a paramount effector of signaling in most cell types. IP4 has additional, ill understood functions. We found that IP4 is essential for multiple aspects of lymphocyte development and function and are currently studying the underlying biological and biochemical mechanisms.
In another main project, we are studying molecular and structural mechanisms through which kinases, the second-largest class of targets for immunomodulatory, cytostatic and other drugs, can become drug resistant. We hope that these studies will instruct novel approaches to overcome drug resistance in patients.

Education

Ph.D., Biology, University of Tuebingen, 1996

Awards & Professional Activities

2011 The Leukemia and Lymphoma Society Scholar Award

Selected References

Barouch-Bentov, R., and Sauer, K. Mechanisms of Drug Resistance in Kinases. (2011) Expert Opin. Investig. Drugs. 20; 153-208.

Sauer, K., and Cooke, M.P. Regulation of Immune Cell Development Through Soluble Inositol-1,3,4,5-tetrakisphosphate. (2010) Nature Reviews Immunology 10, 257-271.

Barouch-Bentov, R., Che, J., Lee, C.C., Yang, Y., Herman, A., Jia, Y., Velentza, A., Watson, J., Sternberg, L., Kim, S., Ziaee, N., Miller, A., Jackson, C., Fujimoto, M., Young, M., Batalov, S., Liu, Y., Warmuth, M., Wiltshire, T., Cooke, M.P., and Sauer, K. (2009) A Conserved Salt Bridge in the G Loop of Multiple Protein Kinases Is Important for Catalysis and for in Vivo Lyn Function. Molecular Cell 33, 43-52.

Huang, Y. H., Grasis, J., Miller, A. T., Xu, R., Soonthornvacharin, S., Andreotti, A. H., Tsoukas, C. D., Cooke, M. P., and Sauer, K. (2007) Positive Regulation of Itk PH Domain Function by Soluble IP₄. Science 316, 886-889.

Links

News & Views: Scientists Identify New Regulatory Mechanism for Critical Protein Signaling Domain

Researchers Discover New Structural Motif in Key Enzymes Is Essential to Prevent Autoimmune Disease