The main goals of the Lung Inflammatory Disease-Program of Excellence in Glycosciences (LID-PEG) are to identify natural ligands for siglecs, to generate novel glycan decorated nanoparticles, and to test the effectiveness of these ligands and mimetics in treating lung inflammation and related responses in vivo in mouse models of allergic asthma and COPD. Core D will help the investigators of this LID-PEG to achieve their goals. The Animal Models Core has established and is using a set of mouse models of allergic asthma and COPD. Core D will also generate several new strains of transgenic humanized and knockout mice to study mechanisms in the regulation of siglec ligand synthesis in the lung and to test the identified and synthesized ligands or mimetics in treating lung inflammation. The core will maintain and make available the lung inflammation models for the investigators of the LID-PEG and will help the investigators of the individual projects to design and perform the experiments and to interpret the results. Core D will also act as a training site for students and postdoctoral fellows with glycobiology background to gain experience in lung biology. The Core utilizes molecular, cellular, immunological, histological and physiological technology and methods to analyze the effects of siglec-targeted ligands on eosinophilic and neutrophilic inflammation and its consequences on other pathological features in those models. In addition, the Core will offer help in preparing mouse lung epithelial cells and eosinophils for ex vivo and in vitro experiments. The Core offers a full range of technical support in analyzing the phenotype change and responses of the newly generated transgenic and knockout mice and those of the lung inflammation models to the treatment of siglec-targeted ligands.

Public Health Relevance

The Animal Models Core is an essential part of the LID-PEG program. The studies on the glycan ligands of siglecs of the inflammatory effector cells in the animal models provided by the core will gain insight into the glycobiology of lung inflammation and will help in the development of novel treatments for inflammatory diseases of the lung.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL107151-04
Application #
8669113
Study Section
Special Emphasis Panel (ZHL1-CSR-H)
Project Start
Project End
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
4
Fiscal Year
2014
Total Cost
$196,640
Indirect Cost
$78,107
Name
Johns Hopkins University
Department
Type
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Robida, Piper A; Puzzovio, Pier Giorgio; Pahima, Hadas et al. (2018) Human eosinophils and mast cells: Birds of a feather flock together. Immunol Rev 282:151-167
O'Sullivan, Jeremy A; Carroll, Daniela J; Cao, Yun et al. (2018) Leveraging Siglec-8 endocytic mechanisms to kill human eosinophils and malignant mast cells. J Allergy Clin Immunol 141:1774-1785.e7
O'Sullivan, Jeremy A; Wei, Yadong; Carroll, Daniela J et al. (2018) Frontline Science: Characterization of a novel mouse strain expressing human Siglec-8 only on eosinophils. J Leukoc Biol 104:11-19
Edgar, Landon J; Kawasaki, Norihito; Nycholat, Corwin M et al. (2018) Targeted Delivery of Antigen to Activated CD169+ Macrophages Induces Bias for Expansion of CD8+ T Cells. Cell Chem Biol :
Khoury, Paneez; Bochner, Bruce S (2018) Consultation for Elevated Blood Eosinophils: Clinical Presentations, High Value Diagnostic Tests, and Treatment Options. J Allergy Clin Immunol Pract 6:1446-1453
Chen, Zi; Bai, Fang-Fang; Han, Lu et al. (2018) Targeting Neutrophils in Severe Asthma via Siglec-9. Int Arch Allergy Immunol 175:5-15
O'Sullivan, Jeremy A; Bochner, Bruce S (2018) Eosinophils and eosinophil-associated diseases: An update. J Allergy Clin Immunol 141:505-517
Bochner, Bruce S (2018) The eosinophil: For better or worse, in sickness and in health. Ann Allergy Asthma Immunol 121:150-155
Gonzalez-Gil, Anabel; Porell, Ryan N; Fernandes, Steve M et al. (2018) Sialylated keratan sulfate proteoglycans are Siglec-8 ligands in human airways. Glycobiology 28:786-801
Khoury, Paneez; Akuthota, Praveen; Ackerman, Steven J et al. (2018) Revisiting the NIH Taskforce on the Research needs of Eosinophil-Associated Diseases (RE-TREAD). J Leukoc Biol 104:69-83

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