This continuation of an established program seeks to prepare qualified M.D., Ph.D., and M.D./Ph.D. candidates for academic careers in the field of allergy and immunology. Support is again requested for eight postdoctoral trainees having either a M.D. or Ph.D. degree or both. The program continues to be highly successful, with over 70% of the graduates in the past decade having full-time academic appointments, most of these being primarily lab based. The training emphasizes the techniques and concepts of cellular and molecular biology applied to fundamental studies of innate and adaptive immune inflammatory responses. The faculty of the program is extensively experienced and successful in training scientists and physician-scientists. The expertise of the faculty includes the basic biology of mast cells, eosinophils, basophils, and dendritic cells;signal transduction via T cell receptors, protein coupled receptors, and Fc?RI pathways;various protein kinases and adaptor proteins;counterregulatory receptors such as gp49B1 and the leukocyte immunoglobulin-like receptors (LIRs) with ITIM motifs to attenuate the activation of mouse mast cells and PMNs and human basophils and eosinophils;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;antigen processing and presentation involving CD1 molecules with a focus on non-protein antigens recognized by NKT cells;characterization of the components of the mast cell secretory granule protease/proteoglycan complex and analysis of their in situ function as assessed in gene disrupted mice;integrin-ligand 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;transcriptional regulation of LTC4 synthase and PGD2 synthase;analysis of the lineage progression and tissue distribution of bipotent mast cell/basophil progenitors and their progeny;utilization of strains lacking biosynthesis of LTC4 (LTC4 synthase null) or receptor-mediated cysteinyl leukotriene signaling (CysLT1R and CysLT2R null strains and double receptor knockouts) to characterize acute and chronic innate and adaptive immune contributions to pulmonary fibrosis and allergic and autoantibody-mediated inflammation, respectively. There is also expertise and training in clinical trials, genetics, and translational medicine. The direct and individualized interactions between each Fellow and the responsible faculty member(s) are augmented by substantial didactic experiences.
Allergic diseases such as asthma, hayfever, and food allergy are a growing public health problem. This grant supports the training of academic scientists and physician-scientists, preparing them for careers as investigators into the causes and treatments of these diseases, with the goal of improving diagnosis, prevention, and therapy of allergic diseases.
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|Kasprowicz, Victoria O; Cheng, Tan-Yun; Ndung'u, Thumbi et al. (2016) HIV Disrupts Human T Cells That Target Mycobacterial Glycolipids. J Infect Dis 213:628-33|
|Lee, Min Jung; Yoshimoto, Eri; Saijo, Shinobu et al. (2016) Phosphoinositide 3-Kinase Î´ Regulates Dectin-2 Signaling and the Generation of Th2 and Th17 Immunity. J Immunol 197:278-87|
|Buchheit, Kathleen M; Cahill, Katherine N; Katz, Howard R et al. (2016) Thymic stromal lymphopoietin controls prostaglandin D2 generation in patients with aspirin-exacerbated respiratory disease. J Allergy Clin Immunol 137:1566-1576.e5|
|Dwyer, Daniel F; Barrett, Nora A; Austen, K Frank et al. (2016) Expression profiling of constitutive mast cells reveals a unique identity within the immune system. Nat Immunol 17:878-87|
|Bankova, L G; Dwyer, D F; Liu, A Y et al. (2015) Maturation of mast cell progenitors to mucosal mast cells during allergic pulmonary inflammation in mice. Mucosal Immunol 8:596-606|
|Cahill, Katherine N; Bensko, Jillian C; Boyce, Joshua A et al. (2015) Prostaglandin Dâ‚‚: a dominant mediator of aspirin-exacerbated respiratory disease. J Allergy Clin Immunol 135:245-52|
|Cardet, Juan-Carlos; Johns, Christina B; Savage, Jessica H (2015) Bacterial metabolites of diet-derived lignans and isoflavones inversely associate with asthma and wheezing. J Allergy Clin Immunol 135:267-9|
|Lee-Sarwar, Kathleen; Johns, Christina; Laidlaw, Tanya M et al. (2015) Tolerance of daily low-dose aspirin does not preclude aspirin-exacerbated respiratory disease. J Allergy Clin Immunol Pract 3:449-51|
|Laidlaw, Tanya M (2015) How Patient Experiences Should Change Our Approach to Treating Patients with Aspirin-Exacerbated Respiratory Disease. J Allergy Clin Immunol Pract 3:719-20|
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