Abstract

The role of the human immune monitoring core (HIMC, Core C) will be to (1) provide standardized, state-ofthe art Immune monitoring assays at the RNA, protein, and cellular level, to support research projects within the U19;(2) to test and develop new technologies for immune monitoring that may be useful In the context of the U19;and (3) to efficiently archive, report, and mine data from immune monitoring studies, so as to increase the value of the data and to assist In biomarker discovery.
Specific Aim 1 : Standardized, state-of-the-art immune monitoring assays. The HIMC has validated a set of Immune monitoring assays that will be available to U19 research projects. These include genome-wide RNA microarrays, multiplex Luminex cytokine assays, immunophenotyping, phosphoepitope flow cytometry, CFSE dye dilution assays for proliferation, and intracellular cytokine staining. An ELISPOT reader is also available for readout of ELISPOT assays.
Specific Aim 2 : New technology for immune monitoring. The HIMC is evaluating multiple new platforms with potential for immune monitoring, including: isoelectric focusing analysis of phosphoproteins (CellBiosciences);chemiluminescent cytokine detection (MesoScale Discovery);biomolecular interaction analysis (ForteBlo);multiplexed tetramer analysis;flow cytometry with time-of-flight mass spectrometry (CyTof);qPCR arrays on sorted cell populations (Fluidigm Blomark);and specialized microarrays for Immunologically relevant genes and for pathogen detection (Agilent).
Specific Aim 3 : Databaslng. The HIMC is Implementing the use of collaborative online databases for flow cytometry, Luminex, and microarray data, and is also evaluating data aggregation and mining programs such as Tibco Spotfire.

Public Health Relevance

The use of standardized assays and data management will facilitate mining across studies and greatly Increase the value of the data for discovery of new biomarkers of vaccine efficacy and disease protection. New technology developed may create opportunities to discover such biomarkers In ways not possible before.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI090019-04
Application #
8509596
Study Section
Special Emphasis Panel (ZAI1-QV-I)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
4
Fiscal Year
2013
Total Cost
$471,062
Indirect Cost
$141,414

  Institution

Name
Stanford University
Department
Type
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305

  Publications

Bongen, Erika; Vallania, Francesco; Utz, Paul J et al. (2018) KLRD1-expressing natural killer cells predict influenza susceptibility. Genome Med 10:45
Cheung, Peggie; Vallania, Francesco; Warsinske, Hayley C et al. (2018) Single-Cell Chromatin Modification Profiling Reveals Increased Epigenetic Variations with Aging. Cell 173:1385-1397.e14
Nair, Nitya; Feng, Ningguo; Blum, Lisa K et al. (2017) VP4- and VP7-specific antibodies mediate heterotypic immunity to rotavirus in humans. Sci Transl Med 9:
Brodin, Petter; Davis, Mark M (2017) Human immune system variation. Nat Rev Immunol 17:21-29
Haddon, D James; Wand, Hannah E; Jarrell, Justin A et al. (2017) Proteomic Analysis of Sera from Individuals with Diffuse Cutaneous Systemic Sclerosis Reveals a Multianalyte Signature Associated with Clinical Improvement during Imatinib Mesylate Treatment. J Rheumatol 44:631-638
Furman, David; Chang, Junlei; Lartigue, Lydia et al. (2017) Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states. Nat Med 23:174-184
HIPC-CHI Signatures Project Team; HIPC-I Consortium (2017) Multicohort analysis reveals baseline transcriptional predictors of influenza vaccination responses. Sci Immunol 2:
O'Gorman, W E; Kong, D S; Balboni, I M et al. (2017) Mass cytometry identifies a distinct monocyte cytokine signature shared by clinically heterogeneous pediatric SLE patients. J Autoimmun :
Blazkova, Jana; Gupta, Sarthak; Liu, Yudong et al. (2017) Multicenter Systems Analysis of Human Blood Reveals Immature Neutrophils in Males and During Pregnancy. J Immunol 198:2479-2488
Rubelt, Florian; Bolen, Christopher R; McGuire, Helen M et al. (2016) Individual heritable differences result in unique cell lymphocyte receptor repertoires of naïve and antigen-experienced cells. Nat Commun 7:11112

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