This continuation of an established training program emphasizes the techniques and concepts of cellular and molecular biology applied to fundamental studies of the adaptive immune and inflammatory responses. The faculty of the program is uniquely competent to conduct research and training in the afferent and efferent pathways of the host responses initiated by immune and innate stimuli, including the following areas: signal transduction via the TCR and the FcepsilonRI pathways, respectively, including the role of various protein kinases and adaptor proteins such as the Cbl family; counterregulatory receptors such as gp49B 1 and the leukocyte immunoglobulin-like receptors (LIRs) with ITIM motifs to attenuate the activation of mouse mast cells and human leukocytes; RNA-binding proteins such as TIA and TIAR, that serve as translational repressors in the balance between cell survival and apoptosis; intracellular vesicular traffic from ER to golgi and in the endosome pathway; molecular analysis of the immune response in human and murine systems in terms of function and regulation of T cell-derived cytokines and identification of genetic programs and activation events in T helper cell (Th1/Th2) differentiation; molecular mechanisms in IgE biosynthesis and in primary immunodeficiency diseases; functional and structural characterization of the gamma delta receptor; antigen processing and presentation involving CD1molecules with a focus on non-protein antigens recognized by T cells; characterization of the components of the mast cell secretory granule protease/proteoglycan complex and analysis of their in situ regulation in gene disrupted mice and of their actions by administration of recombinant human and mouse proteases to mice; integrin-counter receptor and chemokine receptor-ligand interactions in the homing of T cells and of mast cell lineage progenitors; cytokine regulation of eicosanoid biosynthesis in human and mouse culture-derived mast cells, and transcriptional regulation of LTC4 synthase and PGD2 synthase; in situ studies of the physiologic/pathobiologic functions of alphaEbetaB7, gp49B1, LTC4 synthase, PGD2 synthase, IP-10, and BLTR1 with gene-disrupted strains on both BALB/c and B6 backgrounds. Although the primary strength of the program resides in the direct and individual character of the interaction in the laboratory between each Fellow and the responsible faculty member(s), substantial didactic experiences supplement the training. Support is again requested for eight postdoctoral trainees having either a M.D. or Ph.D. degree or both and one predoctoral trainee.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Institutional National Research Service Award (T32)
Project #
2T32AI007306-19
Application #
6496405
Study Section
Allergy & Clinical Immunology-1 (AITC)
Program Officer
Prograis, Lawrence J
Project Start
1985-07-01
Project End
2008-03-31
Budget Start
2003-04-01
Budget End
2004-03-31
Support Year
19
Fiscal Year
2003
Total Cost
$466,030
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Chen, Yuezhou; Chaudhary, Neha; Yang, Nicole et al. (2018) Microbial symbionts regulate the primary Ig repertoire. J Exp Med 215:1397-1415
Arroyo, Anna J Chen; Robinson, Lacey B; Downing, N Lance et al. (2018) Occupational exposures and asthma prevalence among US farmworkers: National Agricultural Workers Survey, 2003-2014. J Allergy Clin Immunol Pract 6:2135-2138.e2
Fay, Marta M; Anderson, Paul J (2018) The Role of RNA in Biological Phase Separations. J Mol Biol 430:4685-4701
Liu, Tao; Barrett, Nora A; Kanaoka, Yoshihide et al. (2018) Type 2 Cysteinyl Leukotriene Receptors Drive IL-33-Dependent Type 2 Immunopathology and Aspirin Sensitivity. J Immunol 200:915-927
Lee-Sarwar, Kathleen; Hauser, Russ; Calafat, Antonia M et al. (2018) Prenatal and early-life triclosan and paraben exposure and allergic outcomes. J Allergy Clin Immunol 142:269-278.e15
Eid, Ryan C; Palumbo, Marina L; Laidlaw, Tanya M et al. (2018) A retrospective analysis of esophageal eosinophilia in patients with aspirin-exacerbated respiratory disease. J Allergy Clin Immunol Pract :
Lee-Sarwar, Kathleen; Litonjua, Augusto A (2018) As You Eat It: Effects of Prenatal Nutrition on Asthma. J Allergy Clin Immunol Pract 6:711-718
Kothari, Parul H; Qiu, Weiliang; Croteau-Chonka, Damien C et al. (2018) Role of local CpG DNA methylation in mediating the 17q21 asthma susceptibility gasdermin B (GSDMB)/ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3) expression quantitative trait locus. J Allergy Clin Immunol 141:2282-2286.e6
Schneider, Thomas R; Johns, Christina B; Palumbo, Marina L et al. (2018) Dietary Fatty Acid Modification for the Treatment of Aspirin-Exacerbated Respiratory Disease: A Prospective Pilot Trial. J Allergy Clin Immunol Pract 6:825-831
Ordovas-Montanes, Jose; Dwyer, Daniel F; Nyquist, Sarah K et al. (2018) Allergic inflammatory memory in human respiratory epithelial progenitor cells. Nature 560:649-654

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