Multi-Ethnic Translational Research Optimization (METRO) Lupus Consortium

多民族转化研究优化 (METRO) 狼疮联盟

• 批准号: 9276490
• 负责人: Jill P Buyon
• 金额: $ 49.84万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-24 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9276490
• 关键词: Address; Affect; Alleles; Antibodies; Archives; Asians; Biological; Biopsy; Biopsy Specimen; Blood; Blood specimen; Capillary Endothelial Cell; Cell Separation; Cells; Characteristics; Chronic; Clinical; Clinical Data; Code; Cohort Studies; Comorbidity; Complementary DNA; Copy Number Polymorphism; Cytokine Activation; Deposition; Dermal; Development; Diabetes Mellitus; Diagnostic; Disease; Drug Targeting; Early Diagnosis; Early identification; Early treatment; Endothelial Cells; Enrollment; Ethnic Origin; Evaluation; Flare; Future; Gene Expression; Gene Expression Profile; Genetic Transcription; Goals; Head; Health; Heterogeneity; Hispanics; Histologic; Histones; Human; Incidence; Injury to Kidney; Kidney; Kidney Diseases; Lead; Leucocytic infiltrate; Link; Liquid substance; Longitudinal Studies; Lupus; Lupus Nephritis; Maintenance; Medicine; Messenger RNA; Methods; MicroRNAs; Molecular Analysis; Mutation; Nephritis; Normal tissue morphology; Onset of illness; Organ; Pathologic Processes; Pathway interactions; Patients; Pattern; Peripheral Blood Mononuclear Cell; Phase; Phenotype; Plasma; Population; Prediction of Response to Therapy; Prevalence; Process; Publications; RNA; RNA analysis; Race; Recording of previous events; Recruitment Activity; Recurrent disease; Relapse; Renal Tissue; Renal function; Research Design; Rest; Sampling; Severities; Signal Pathway; Signal Transduction; Site; Skin; Small RNA; Socioeconomic Status; Source; Staging; Structure; Systemic Lupus Erythematosus; Tail; Techniques; Technology; Tissue Banks; Tissues; Transfer RNA; Translational Research; Transplantation; Universities; Untranslated RNA; Urine; Validation; Variant; Vascular Diseases; Woman; base; biobank; candidate identification; clinical application; cohort; college; cost effective; deep sequencing; experience; insight; interest; interstitial; kidney cell; medical schools; new technology; novel therapeutics; patient population; patient stratification; racial and ethnic; racial and ethnic disparities; racial disparity; response; systemic autoimmune disease; therapeutic development; transcriptome; transcriptome sequencing; validation studies

 DESCRIPTION (provided by applicant): Three major academic centers propose to collaborate as a combined clinical-technology site. The 2 clinical centers, NYU School of Medicine and Albert Einstein College of Medicine, have a rich and long history of commitment to SLE and together currently treat ~1,000 SLE patients. They will jointly assemble a renal phenotype-driven patient cohort comprising diverse ethnic/racial backgrounds. The Multi-Ethnic Translational Research Optimization (METRO) Lupus Consortium cohort will be leveraged to develop, standardize and validate advanced technologies to identify critical signaling pathways in tissues (renal and skin), cells and urine. Given the widespread vasculopathy characteristic of SLE, endothelial cell activation in the tubulointerstitium in lupus nephritis (LN) may be accompanied by similar activation, even in nonlesional skin. Molecular analysis of gene expression and signaling in specific subsets of renal cells may precede and predict the pathologic processes that lead to end organ damage and provide insights to deconstruct the heterogeneity of lupus in general and the histologic class of renal disease in particular. Furthermore, the faithful reflection of a relevant pathway in renal tissue by a more readily accessible tissue or fluid compartment would pave the way to early identification and treatment, critical to renal survival. Because SLE is strongly associated with racial/ethnic disparities, studies need to address whether specific biological pathways and drug targets are race-/ethnicity- dependent. Accordingly, METRO will comprise substantial numbers of Black, Hispanic, Asian, and White patients recruited at NYU (PI Buyon) and Einstein (PI Putterman). PI Dr. Thomas Tuschl at The Rockefeller University brings expertise and extensive experience in coding and non-coding RNAseq analysis and RNA diagnostic and therapeutic development. The proposal addresses 2 objectives: i) identification of candidate targets to guide novel therapy; and ii) development of non-invasive strategies to maximize early detection of LN. The former will be approached by identifying unique patterns from single-cell RNAseq (including RNA deregulation or mutation/allelic variation) in LN kidney cells (including capillary endothelial cells) compared with normal tissue/cells, and the latter by similar RNA analysis in LN matched with nonlesional skin, PBMC, and urine cellular pellet (UCP). Operationally the project is approached in sequential phases: Aim 1 (Phase 0, UH2): To establish the optimal method of renal tissue collection and single cell isolation of resident and infiltrating cells followed by poyA RNAseq, and similar application to cell populations present in nonlesional skin, PBMC, and UCP. Aim 2 (Phase I, UH2): To identify RNAseq patterns associated with different biopsy classes and compare with nonlesional skin (endothelial cells), PBMC, and UCP from the same patient. Aim 3 (Phase II, UH3): To establish whether a) the renal tissue RNAseq pattern associates with biopsy class, activity, and chronicity segregated by race/ethnicity; b) renal pattern tracks response to therapy and/or progression of renal disease in new onset or recurrent disease; and c) the pattern in skin, PBMC or UCP antedates new or relapsing kidney involvement.