Cell surface glycans and complementary glycan binding proteins are intimately involved in inflammatory processes. Members of this Program team and others discovered that certain members of the siglec family of glycan binding proteins are inhibitors of inflammation. This Lung Inflammatory Disease Program of Excellence in Glycosciences (LID-PEG) focuses on the anti-inflammatory functions of siglecs and their glycan counter-receptors (ligands) in moderating ongoing inflammation in the lung. THEME: Specific glycans expressed on lung tissues engage complementary glycan binding proteins (Siglec-8, Siglec-9, Siglec-1) on inflammatory cells to limit lung inflammation. Knowledge of the glycan structures and glycan binding proteins involved, the control of their expression, and the mechanisms responsible for translating glycan engagement into regulation of the inflammatory response will provide new insights into the progression of inflammatory lung diseases. Synthetic glycan-decorated nanoparticles and antibodies that target glycan binding proteins on inflammatory cells will limit inflammatory damage. The insights gained may lead to novel diagnostic tools and therapeutic compositions that treat inflammatory diseases of the lung and other tissues relevant to the goals of the NHLBI. Four closely integrated Projects and two Cores at three major glycobiology centers will coordinate efforts to reach the Project goals: Project 1, """"""""Treating lung inflammation by targeting siglecs"""""""" (B. Bochner, Johns Hopkins);Project 2, """"""""Siglec-targeted nanoparticles for lung and cardiovascular disease"""""""" (J. Paulson, Scripps);Project 3, """"""""Human lung counter-receptors for Siglec-8 and Siglec-9"""""""" (R. Schnaar, Johns Hopkins);Project 4, """"""""Regulated expression of siglec counter-receptors"""""""" (M. Tiemeyer, CCRC/U. Georgia);Core C, """"""""Shared Resources Core: Carbohydrate Synthesis"""""""" (J. Paulson, Scripps);and Core D, """"""""Inflammatory Animal Models Core"""""""" (Z. Zhu, Johns Hopkins). The Program is supported by an Administrative Core (Core A) and a Skills Development Core (Core B) that provides trainees with diverse experiences at the three centers. This Program will provide novel insights into the glycosciences of lung inflammatory diseases.

Public Health Relevance

Asthma and Chronic Obstructive Pulmonary Disease (COPD), lung diseases that cause extensive illness and death, involve infiltration of damaging inflammatory cells. Normally, sugar molecules in the lung engage complementary sugar binding molecules on inflammatory cells, signaling them to halt and limiting tissue damage. This project defines anti-inflammatory sugar molecules and uses them to develop new treatments.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL107151-03
Application #
8477244
Study Section
Special Emphasis Panel (ZHL1-CSR-H (F1))
Program Officer
Caler, Elisabet V
Project Start
2011-07-01
Project End
2018-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
3
Fiscal Year
2013
Total Cost
$2,058,671
Indirect Cost
$412,474
Name
Johns Hopkins University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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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

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