Laboratory for Allergic Disease

Research Areas

We study fundamental processes of mast cell biology with the long-term goal of identifying drug targets to treat allergic diseases such as asthma, atopic dermatitis, food allergy and allergic rhinitis.

1. Histamine-releasing factor (HRF) is a multifunctional protein with both intracellular and extracellular functions. Its intracellular functions include cell-cycle progression, survival, proliferation and malignant transformation of various cells. On the other hand, secreted HRF has been implicated in allergic diseases. We recently demonstrated that HRF directly interacts with a subset of IgE and IgG molecules and plays a critical role in promoting allergic inflammation in animal models of asthma, skin hypersensitivity and food allergy. We will study the role of HRF in human allergic diseases and seek the potential application of HRF blockage in treating allergic patients.
2. Pathogenic roles of mast cells in atopic dermatitis are studied at molecular and cellular network levels. Our recent studies raise the hope to develop novel therapeutics in this area.
3. Mast cell activation through the high-affinity IgE receptor (FcεRI) is critically involved in allergic diseases. Therefore, we will continue to study FcεRI-mediated signaling events to identify critical checkpoints that can be drug targets for future pharmacological intervention.

Research Fields

Biology & Biochemistry / Molecular Biology & Genetics / Immunology

Research Subjects

• Roles of HRF in allergic diseases
• Pathogenesis and treatment of atopic dermatitis
• Mast cell activation via FcεRI

Publications

1. Xiao, W., Hong, H., Kawakami, Y., Lowell, C. A., and Kawakami, T.:
   "Regulation of myeloproliferation and M2 macrophage programming by Lyn/Hck, SHIP and Stat5."
   J. Clin. Invest. 118, 924-934 (2008).
2. Kawakami, T.:
   "Basophils now enhance memory."
   Nat. Immunol. 9, 720-721 (2008).
3. Kawakami, Y., Tomimori, Y., Yumoto, K., Hasegawa, S., Ando, T., Tagaya, Y., Crotty, S., and Kawakami, T.:
   "Inhibition of NK cell activity by IL-17 vaccinia virus to induce severe skin lesions in a mouse model of eczema vaccinatum."
   J. Exp. Med. 206, 1219-1225 (2009).
4. Xiao, W., Hong, H., Kawakami, Y., Kato, Y., Wu, D., Yasudo, H., Kimura, A., Kubagawa, H., Bertoli, L. F., Davis, R. S., Chau, L. A., Madrenas. J., Hsia, C. C., Xenocostas. A., Kipps, T. J., Hennighausen, L., Iwama, A., Nakauchi, H., and Kawakami, T.:
   "Tumor suppression by phospholipase C-β3 via SHP-1-mediated dephosphorylation of Stat5."
   Cancer Cell 16, 161-171 (2009).
5. Andrews, N. L., Pfeiffer, J. R., Martinez, A. M., Haaland, D. M., Davis, R. W., Kawakami, T., Oliver, J. M., Wilson, B. S., and Lidke, D. S.:
   "Small, mobile FcεRI aggregates are signaling competent."
   Immunity 31, 1-11 (2009).
6. Kawakami, T., Ando, T., Kimura, M., Wilson, B.S., and Kawakami, Y.:
   "Mast cells in atopic dermatitis."
   Curr. Opin. Immunol. 21, 666-678 (2009).
7. Xiao, W., Kashiwakura, J., Hong, H., Yasudo, H., Ando, T., Maeda-Yamamoto, M., Wu, D., Kawakami, Y., and Kawakami, T.:
   "Phospholipase C-β3 regulates FcεRI-mediated mast cell activation by recruiting the protein phosphatase SHP-1."
   Immunity 34, 893-904 (2011).
8. Kashiwakura, J.*, Ando, T.*, Matsumoto, K., Kimura, M., Zajonc, D.M., Ozeki, T., Siraganian, R.P., Broide, D., Kawakami, Y., and Kawakami, T.:
   "Histamine-releasing factor has a proinflammatory role in mouse models of asthma and allergy."
   J. Clin. Invest. 122, 218-228 (2012).