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Benaroya Research Institute at Virginia Mason
Jessica Hamerman received her B.S. in Biological Sciences from Stanford University and her Ph.D. in Immunology from the University of Washington. She then pursued postdoctoral studies at the University of California San Francisco before joining the Benaroya Research Institute Immunology Program. Detailed Description of Work Research in our laboratory focuses on the regulation of the innate immune response to pathogens with an emphasis on macrophages and dendritic cells. Macrophages and dendritic cells are distributed throughout the body where they are poised to detect pathogens and to subsequently alert the immune system to the presence of infection through the production of inflammatory mediators. The production of inflammatory mediators, such as tumor necrosis factor (TNF) and other pro-inflammatory cytokines, is tightly regulated. Although these important cytokines are beneficial to the host for pathogen clearance, they can be detrimental if unchecked. This can be seen in septic shock as well as in autoimmune disorders such as rheumatoid arthritis. Macrophages and dendritic cells recognize pathogens by a variety of cell surface and intracellular receptors termed pattern recognition receptors, including the family of Toll-like receptors (TLR). We study how signaling through pattern recognition receptors results in the appropriate inflammatory response by macrophages and dendritic cells. We are particularly interested in proteins that inhibit signaling through pattern recognition receptors, providing an essential check to the inflammatory response. These studies will not only help elucidate how inflammatory cytokine production is regulated during infection, but will potentially give insights in how to manipulate the innate immune system to achieve more efficient elimination of pathogens and to regulate the inflammatory response during disease. This is a topic of significance in the development of vaccines and immunomodulatory drugs to prevent and treat infections as well as to regulate inflammatory diseases. Two proteins we study in this regard are TREM-2 and DAP12, which together make up a receptor signaling complex expressed on macrophages and dendritic cells. TREM-2 is an Ig superfamily receptor without its own signaling capacity that associates with DAP12, an ITAM (immunoreceptor tyrosine-based activation motif)-containing transmembrane signaling adapter, to transduce signals. Macrophages lacking DAP12 or TREM-2 have increased inflammatory cytokine production after stimulation through TLRs demonstrating their function in inhibiting TLR responses. This was a surprising function for an activating receptor complex and we are studying several aspects of this system. This includes the signal transduction, the receptor-ligand interactions and the in vivo biology of TREM-2/DAP12 inhibition of TLR-based inflammatory responses. Publications Hamerman, J. A., Jarjoura, J. R., Humphrey, M. B., Nakamura, M. C., Seaman, W. E., and Lanier, L. L. Cutting edge: inhibition of TLR and FcR responses in macrophages by triggering receptor expressed on myeloid cells (TREM)-2 and DAP12 J. Immunol. 177:2051-2055, 2006 Hamerman, J. A. and Lanier, L. L. Inhibition of immune responses by ITAM-bearing receptors Sci. STKE. 2006:re1-2006 Hamerman, J. A., Tchao, N. K., Lowell, C. A., and Lanier, L. L. Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12 Nat. Immunol. 6:579-586, 2005 Ehrlich, L. I., Ogasawara, K., Hamerman, J. A., Takaki, R., Zingoni, A., Allison, J. P., and Lanier, L. L. Engagement of NKG2D by cognate ligand or antibody alone is insufficient to mediate costimulation of human and mouse CD8+ T cells J. Immunol. 174:1922-1931, 2005 Hamerman, J. A., Ogasawara, K., and Lanier, L. L. NK cells in innate immunity Curr. Opin. Immunol. 17:29-35, 2005 Rosen, D. B., Araki, M., Hamerman, J. A., Chen, T., Yamamura, T., and Lanier, L. L. A Structural basis for the association of DAP12 with mouse, but not human, NKG2D J. Immunol. 173:2470-2478, 2004 Ogasawara, K., Hamerman, J. A., Ehrlich, L. R., Bour-Jordan, H., Santamaria, P., Bluestone, J. A., and Lanier, L. L. NKG2D blockade prevents autoimmune diabetes in NOD mice Immunity. 20:757-767, 2004 Hamerman, J. A., Ogasawara, K., and Lanier, L. L. Cutting edge: Toll-like receptor signaling in macrophages induces ligands for the NKG2D receptor J. Immunol. 172:2001-2005, 2004 Lodoen, M., Ogasawara, K., Hamerman, J. A., Arase, H., Houchins, J. P., Mocarski, E. S., and Lanier, L. L. NKG2D-mediated natural killer cell protection against cytomegalovirus is impaired by viral gp40 modulation of retinoic acid early inducible 1 gene molecules J. Exp. Med. 197:1245-1253, 2003 Zompi, S., Hamerman, J. A., Ogasawara, K., Schweighoffer, E., Tybulewicz, V. L., Di Santo, J. P., Lanier, L. L., and Colucci, F. NKG2D triggers cytotoxicity in mouse NK cells lacking DAP12 or Syk family kinases Nat. Immunol. 4:565-572, 2003 Ogasawara, K., Hamerman, J. A., Hsin, H., Chikuma, S., Bour-Jordan, H., Chen, T., Pertel, T., Carnaud, C., Bluestone, J. A., and Lanier, L. L. Impairment of NK cell function by NKG2D modulation in NOD mice Immunity. 18:41-51, 2003 Cerwenka, A., O'Callaghan, C. A., Hamerman, J. A., Yadav, R., Ajayi, W., Roopenian, D. C., Joyce, S., and Lanier, L. L. Cutting edge: the minor histocompatibility antigen H60 peptide interacts with both H-2Kb and NKG2D J. Immunol. 168:3131-3134, 2002 Hamerman, J. A., Hayashi, F., Schroeder, L. A., Gygi, S. P., Haas, A. L., Hampson, L., Coughlin, P., Aebersold, R., and Aderem, A. Serpin 2a is induced in activated macrophages and conjugates to a ubiquitin homolog J. Immunol. 168:2415-2423, 2002 Hamerman, J. A. and Aderem, A. Functional transitions in macrophages during in vivo infection with Mycobacterium bovis bacillus Calmette-Guerin J. Immunol. 167:2227-2233, 200 Morrissette, N. S., Gold, E. S., Guo, J., Hamerman, J. A., Ozinsky, A., Bedian, V., and Aderem, A. A. Isolation and characterization of monoclonal antibodies directed against novel components of macrophage phagosomes J. Cell Sci. 112 ( Pt 24):4705-4713, 1999 Page, S. T., Bogatzki, L. Y., Hamerman, J. A., Malissen, M., Perlmutter, R. M., and Pullen, A. M. Differential effects of manipulating signaling in early T cell development in intestinal intraepithelial lymphocytes and thymocytes Int. Immunol. 11:169-177, 1999 Page, S. T., Bogatzki, L. Y., Hamerman, J. A., Sweenie, C. H., Hogarth, P. J., Malissen, M., Perlmutter, R. M., and Pullen, A. M. Intestinal intraepithelial lymphocytes include precursors committed to the T cell receptor alpha beta lineage Proc. Natl. Acad. Sci. U. S. A 95:9459-9464, 1998 Hamerman, J. A., Page, S. T., and Pullen, A. M. Distinct methylation states of the CD8 beta gene in peripheral T cells and intraepithelial lymphocytes J. Immunol. 159:1240-1246, 1997
Posted February 2007
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