Faculty

Karsten Sauer 
Assistant Professor
Immunology and Microbial Science
TSRI - 2006

Education 
Ph.D., University of Tuebingen, Germany, 1996.

Research Focus 
Mechanisms of Antigen Receptor Signaling in T Cell Development and Function

T cells defend us against infections by recognizing pathogen derived antigens through their T cell receptor (TCR). Perturbed TCR signaling can lead to immunodeficiency or to the emergence of T cells recognizing innocuous antigens, resulting in allergies or autoimmune diseases. Our core interest are the mechanisms by which TCR signaling directs T cell development and function. Through the identification of novel genes involved in TCR signaling and detailed functional analyses of their encoded proteins, we hope to improve our understanding of the molecular mechanisms regulating T cell development, function and malfunction in disease.

To identify such genes and develop hypotheses about their functions, we take advantage of large scale functional genomics approaches initiated in collaboration with GNF. At TSRI, we complement these with detailed, hypothesis-driven functional analyses of selected genes, combining genetic, biochemical, molecular biological, cell biological, pharmacological and immunological approaches to determine their functions in vivo and their precise mechanisms of action in detail. In one intriguing example, the identification of a mouse mutant deficient in Inositol(1,4,5)trisphosphate 3-kinase B led us to the discovery of a novel role for the soluble small molecule Inositol(1,3,4,5)tetrakisphosphate (IP₄) as a positive in vivo regulator of PH domains, critical modules which mediate protein recruitment to cellular membranes. In the thymus, this IP₄ function is essential for positive selection of developing T cells, a process whereby functional precursors are induced to mature into functional T cells. Current research in the lab aims at the definition of the precise molecular mechanisms through which IP₄ regulates PH domain function and thymocyte positive selection.

Selected References 
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.

Miller, A. T., Sandberg, M., Huang, Y. H., Young, M., Sutton, S., Sauer, K., and Cooke, M. P. (2007) Production of Ins(1,3,4,5)P₄ mediated by the kinase Itpkb inhibits store-operated calcium channels and regulates B cell selection and activation. Nature Immunology 8, 514-521.

Huang, Y. H., Hoebe, K., and Sauer, K. (2008) New therapeutic targets in immune disorders: ItpkB, Orai1 and UNC93B.Expert Opin Ther Targets 12, 391-413.

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.