Jessica Hamerman, Ph.D.
Affiliate Assistant Professor, Immunology

Benaroya Research Institute at Virginia Mason
1201 Ninth Avenue
Seattle, WA 98101-2795
Tel: 206.341-1317
Fax: 206.223-7543
Email: jhamerman@benaroyaresearch.org

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 and systemic lupus erythematosus.

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 brake 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. 

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, and signals through, DAP12, an ITAM (immunoreceptor tyrosine-based activation motif)-containing transmembrane signaling adapter. 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.  We are also examining how this inhibitory pathway functions in dendritic cells, and investigating how several other macrophage and dendritic cells receptors regulate the inflammatory response.

Students currently training in the Hamerman lab: Nathan Yee

Selected Publications

N'Diaye EN, Branda CS, Branda SS, Nevarez L, Colonna M, Lowell C, Hamerman JA, Seaman WE (2009) TREM-2 (triggering receptor expressed on myeloid cells 2) is a phagocytic receptor for bacteria. J Cell Biol. 2009 Jan 26;184(2):215-23

Chu CL, Yu YL, Shen KY, Lowell CA, Lanier LL, Hamerman JA (2008) Increased TLR responses in dendritic cells lacking the ITAM-containing adapters DAP12 and FcRg, European Journal of Immunology, 38 (1), 166-73.

Epardaud M, Elpek KG, Rubinstein MP, Yonekura AR, Bellemare-Pelletier A, Bronson R, Hamerman JA, Goldrath AW, Turley SJ (2008) Interleukin-15/interleukin-15R alpha complexes promote destruction of established tumors by reviving tumor-resident CD8+ T cells. Cancer Res. 68(8):2972-83.

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

Hamerman, J. A., Ogasawara, K., and Lanier, L. L. NK cells in innate immunity Curr. Opin. Immunol. 17:29-35, 2005

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

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

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, 2000.

Updated 8/19/09