Keli Hippen PhD
Instructor
Keli.L.Hippen-1@tc.umn.edu
Current Project(s) :
I am currently working on two projects related to B cell autoimmune diseases
The first project stems from my discovery that self-reactive B cells express an inhibitory molecule called CD5. Self-reactive B cells from mutant mice lacking CD5 break tolerance and secrete autoantibodies. However not all mice develop significant autoantibody titers. This phenotype suggests tolerance in CD5 knockout mice, like human autoimmune disease, is affected by environmental factors. Experiments are currently under way to determine what these environmental factors are.
In addition to the CD5 project, we are also developing a better murine model of autoimmune disease. The current model of choice employs a transgenic B cell receptor specific for Hen Egg Lysozyme. This transgenic immunoglobulin cannot class switch, so breaks in tolerance only result in IgM autoantibody. However, pathogenic antibodies involved in human autoimmune disease are primarily IgG isotypes. Therefore, we are developing a knock-in model of B cell tolerance that still uses the Hen Egg Lysozyme specificity.
C.V. :
Hippen, K.L., Soucy, A., Rosenberg, M., Pape, K.A., Jenkins, M.C., & Behrens, T.W. (2003). Loss of B Cell Anergy in HEL-Ig/sHEL Mice Carrying Two Copies of the Transgene Encoding the Hen Egg Lysozyme Specific Immunoglobulin. Nature Immunology (Manuscript in preparation).
Tze, L.T., Baness, E.A., Hippen, K.L., & Behrens, T.W. (2000). Immunoglobulin Light Chain Receptor Editting in Anergic B Cells. J. Immunol. 165: 6796-6802.
Hippen, K.L., Tze, L., & Behrens, T.W. (2000). CD5 Maintains Tolerance in Anergic B Cells. J. Exp. Med 191: 883-890.
Hippen, K.L., Tze, L., & Behrens, T.W. (1999). Workshop Presentation at Keystone Symposia (B Lymphocyte Biology and Disease). CD5 is Expressed on Anergic B cells and Functions to Inhibit BCR Mediated Proliferation and Antibody Secretion.
Hippen, K.L., Buhl, A.M., D'Ambrosio, D., Nakamura, K., Persin, C., & Cambier, J.C. (1996). FcgRIIB1 Inhibition of BCR-Mediated Phosphoinositide Hydrolysis and Ca2+ Mobilization Is Integrated by CD19 Dephosphorylation. Immunity 7: 49-58.
D'Ambrosio, D.*, Hippen, K.L., Minskoff, S.A., Mellman, I., Pani, G., Siminovitch, K.A., & Cambier, J.C. (1995). Recruitment and Activation of PTP-1C in Negative Regulation of Antigen Receptor Signaling by FcgRIIB1. Science 268: 293-297.
*: K.H. and D. D. contributed equally to this work.
Ingebritsen, T. S., Hiriyana, K. T., & Hippen, K. L. (1994). Protein phosphatases in Cell Proliferation, Differentiation, and Development. In Growth Factors and Signal Transduction in Development. Nilsen-Hamilton, M. Ed. New York: Wiley Liss, pp 139-163.
Hippen, K. L., Jakes, S., Richards, J., Jena, B. P., Beck, B. L., Tabatabai, L. B., & Ingebritsen, T. S. (1993) Acidic residues are involved in substrate recognition by two intracellular protein tyrosine phosphatases, PTP-5 and rrbPTP-1. Biochemistry 32: 12405-12415.
Hobbies :
Baseball, gardening, music
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