Research Program:
The Gelfand laboratory's major focus is on defining the role of the immune system in the development of allergic diseases and asthma in particular, using specific mouse models of airway hyperresponsiveness and inflammation following exposure to allergen, virus, or ozone. Currently the major areas of investigation include defining the role of effector memory CD8+ T cells in asthma, the essential contributions of lipid mediators to the recruitment and activation of these T cells, the role of naturally occurring T regulatory cells, and the importance of Notch-Notch-ligand interactions on antigen presenting cells. In these studies emphasis has been placed on defining the critical signaling pathways in T cells and mast cells.
An associated area of interest is primary immunodeficiency, linking the clinical program, immune reconstitution and genetic definition of patients presenting with suspected immunodeficiency.

Animal Models:
The study of allergen, virus and ozone induced airway hyperresponsiveness and inflammation Signaling The study of T cell and mast cell signaling pathways leading to cell activation and cytokine transcriptional regulation Immunodeficiency Defining the genetic defects in patients with primary immunodeficiency and options for immune reconstitution

Key Publications:

• Miyahara N, Swanson BJ, Takeda K, Taube C, Miyahara S, Kodama T, Dakhama A, Ott V, and Gelfand EW.  Effector memory CD8+ T cells mediate airway hyperresponsiveness, inflammation and remodeling.  Nature Med. 10:865-869, 2004.
• Dakhama A, Park JW, Taube C, Joetham A, Balhorn A, Miyahara N, Takeda K, and Gelfand EW. The enhancement or prevention of airway hyperresponsiveness during re-infection with respiratory syncytial virus is critically dependent on the age at first infection and interleukin-13 production. J. Immunol. 175:1876-1883, 2005.
• Matsubara S, Koya T, Takeda K, Joetham A, Miyahara N, Pine P, Masuda ES, Swasey CH, and Gelfand EW.  Syk activation in dendritic cells is essential for airway hyperresponsiveness and inflammation.  Amer. J. Resp. Cell Mol. Biol. 34:426-433, 2006.
• Joetham A, Takeda K, Miyahara N, Matsubara S, Ohnishi H, Koya T, Dakhama A, and Gelfand EW.  Activation of naturally occurring lung CD4+CD25+ regulatory T cells requires CD8 and MHC I interaction.  Proc. Natl. Acad. Sci. 104:15057-15062, 2007.
• Joetham A, Matsubara S, Okamoto M, Takeda K, Miyahara N, Dakhama A, and Gelfand EW.  Plasticity of naturally occurring regulatory T cells: Subversion of suppressive function and conversion to enhancement of lung allergic responses.  J. Immunol. 180:7117-7124, 2008.
• Okamoto M, Takeda K, Joetham A, Ohnishi H, Matsuda H, Swasey CH, Yasutomo K, Dakhama A, and Gelfand EW. Essential role of Notch signaling in effector memory CD8+ T cell-mediated airway hyperresponsiveness and inflammation.  J. Exp. Med., 205:1087-1097, 2008.
• Okamoto M, Takeda K, Joetham A, Ohnishi H, Matsuda H, Swasey CH, Yasutomo K, Dakhama A, and Gelfand EW. Essential role of Notch signaling in effector memory CD8+ T cell-mediated airway hyperresponsiveness and inflammation.  J. Exp. Med., 205:1087-1097, 2008.
• Miyahara N, Matsuda H, Miyahara S, Takeda K, Ohnishi H, Koya T, Matsubara S, Okamoto M, Dakhama A, Haribabu B, and Gelfand EW.  Leukotriene B4 receptor-1 (BLT1) expression on dendritic cells is required for the development of Th2 responses and allergen-induced airway hyperresponsiveness. J. Immunol., in press, 2008.

Honorary Fellowship from the American Academy of Allergy, Asthma and Immunology Mead-Johnson Award for Research in Pediatrics Lifetime Achievement Award from National Jewish Health

View of Recent Publications in PubMed