Our laboratory has developed a technology to combine proteomic, phosphoproteomic, and genomic biomarkers simultaneously in a clinically relevant and clinically applicable manner. As the Multi-parameter Flow Cytometric Genomics Core, we will be applying our novel multiplexing technology to address the following specific aims. 1) Develop the application of multiparameter flow cytometry gene expression profiling to deconvolute the evolution of the immune response in the peripheral blood to a kidney or heart transplant. We will combine an array of lineage- and activation-specific antibodies that define each cell subset and its state and simultaneous multi-parameter mRNA transcript detection in a single run. 2) Develop the application of multiparameter flow cytometry proteomics to deconvolute the evolution of the immune response in the peripheral blood to a kidney or heart transplant. We will combine the same array of lineage- and activation-specific antibodies that define each cell subset and its state used in Aim 1 and simultaneous multi-parameter protein and/or phosphoprotein detection in a single run. 3) Develop the diagnostic applications of multiparameter flow cytometry done as a function of time following kidney and heart transplantation to identify blood cell subset-specific changes in composition and cell activation during a recognized clinical event or predicting rejection. We will also correlate changes in cell subset composition as a function of time, clinical events and outcomes with the whole blood profiling of gene transcripts, alternative splicing, miRNA expression and phosphoproteomlcs done in parallel on the same clinical samples by Project #1 and Project #2.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI063603-10
Application #
8522123
Study Section
Special Emphasis Panel (ZAI1-MFH-I)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
10
Fiscal Year
2013
Total Cost
$130,758
Indirect Cost
$33,046
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Leventhal, J R; Mathew, J M; Salomon, D R et al. (2016) Nonchimeric HLA-Identical Renal Transplant Tolerance: Regulatory Immunophenotypic/Genomic Biomarkers. Am J Transplant 16:221-34
LaMere, S A; Thompson, R C; Komori, H K et al. (2016) Promoter H3K4 methylation dynamically reinforces activation-induced pathways in human CD4 T cells. Genes Immun 17:283-97
Modena, B D; Milam, R; Harrison, F et al. (2016) Changes in Urinary Microbiome Populations Correlate in Kidney Transplants With Interstitial Fibrosis and Tubular Atrophy Documented in Early Surveillance Biopsies. Am J Transplant :
Savaryn, John P; Toby, Timothy K; Catherman, Adam D et al. (2016) Comparative top down proteomics of peripheral blood mononuclear cells from kidney transplant recipients with normal kidney biopsies or acute rejection. Proteomics 16:2048-58
Weinsheimer, Shantel; Bendjilali, Nasrine; Nelson, Jeffrey et al. (2016) Genome-wide association study of sporadic brain arteriovenous malformations. J Neurol Neurosurg Psychiatry 87:916-23
Kurian, S M; Fouraschen, S M G; Langfelder, P et al. (2015) Genomic profiles and predictors of early allograft dysfunction after human liver transplantation. Am J Transplant 15:1605-14
Norden-Krichmar, Trina M; Gizer, Ian R; Phillips, Evelyn et al. (2015) Variants Near CCK Receptors are Associated With Electrophysiological Responses to Pre-pulse Startle Stimuli in a Mexican American Cohort. Twin Res Hum Genet 18:727-37
Magdeldin, Sameh; Blaser, Rachel E; Yamamoto, Tadashi et al. (2015) Behavioral and proteomic analysis of stress response in zebrafish (Danio rerio). J Proteome Res 14:943-52
Komori, H Kiyomi; Hart, Traver; LaMere, Sarah A et al. (2015) Defining CD4 T cell memory by the epigenetic landscape of CpG DNA methylation. J Immunol 194:1565-79
Routh, Andrew; Head, Steven R; Ordoukhanian, Phillip et al. (2015) ClickSeq: Fragmentation-Free Next-Generation Sequencing via Click Ligation of Adaptors to Stochastically Terminated 3'-Azido cDNAs. J Mol Biol 427:2610-6

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