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 #
2U19AI063603-08
Application #
8224784
Study Section
Special Emphasis Panel (ZAI1-MFH-I (M2))
Project Start
Project End
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
8
Fiscal Year
2011
Total Cost
$182,287
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Kurian, S M; Velazquez, E; Thompson, R et al. (2017) Orthogonal Comparison of Molecular Signatures of Kidney Transplants With Subclinical and Clinical Acute Rejection: Equivalent Performance Is Agnostic to Both Technology and Platform. Am J Transplant 17:2103-2116
Buzby, Jeffrey S; Williams, Shirley A; Schaffer, Lana et al. (2017) Allele-specific wild-type TP53 expression in the unaffected carrier parent of children with Li-Fraumeni syndrome. Cancer Genet 211:9-17
Modena, Brian D; Bleecker, Eugene R; Busse, William W et al. (2017) Gene Expression Correlated with Severe Asthma Characteristics Reveals Heterogeneous Mechanisms of Severe Disease. Am J Respir Crit Care Med 195:1449-1463
LaMere, Sarah A; Thompson, Ryan C; Meng, Xiangzhi et al. (2017) H3K27 Methylation Dynamics during CD4 T Cell Activation: Regulation of JAK/STAT and IL12RB2 Expression by JMJD3. J Immunol 199:3158-3175
Oetting, W S; Schladt, D P; Guan, W et al. (2016) Genomewide Association Study of Tacrolimus Concentrations in African American Kidney Transplant Recipients Identifies Multiple CYP3A5 Alleles. Am J Transplant 16:574-82
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
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
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
Modena, B D; Kurian, S M; Gaber, L W et al. (2016) Gene Expression in Biopsies of Acute Rejection and Interstitial Fibrosis/Tubular Atrophy Reveals Highly Shared Mechanisms That Correlate With Worse Long-Term Outcomes. Am J Transplant 16:1982-98
Kurian, Sunil M; Novais, Marta; Whisenant, Thomas et al. (2016) Peripheral Blood Cell Gene Expression Diagnostic for Identifying Symptomatic Transthyretin Amyloidosis Patients: Male and Female Specific Signatures. Theranostics 6:1792-809

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