Stanford Technology Accelerating Medicines Partnership Center

斯坦福大学技术加速药物合作中心

• 批准号: 10208564
• 负责人: William H Robinson
• 金额: $ 2.5万
• 依托单位: STANFORD UNIVERSITY
• 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 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10208564
• 关键词: Adverse event; Antibodies; Antigen Targeting; Antigens; Area; Autoantibodies; Autoantigens; Autoimmune Diseases; Autoimmunity; B-Lymphocytes; Bar Codes; Binding; Biological; Biological Assay; Biotechnology; Blood; Blood Cells; Blood specimen; California; Cell surface; Cells; Chromatin; Collaborations; Colorado; Data Set; Databases; Dendritic Cells; Development; Disease; Disease Outcome; Drug Targeting; Epigenetic Process; Epitopes; Fc Receptor; Flare; Freezing; Funding; Future; Gene Proteins; Genes; Genetic; Genetic Transcription; Genomics; Goals; Growth Factor; High-Throughput Nucleotide Sequencing; Human; Immune; Immune Targeting; Immune response; Immune system; Immunologic Monitoring; Individual; Kidney; Leadership; Letters; Light; Malignant Neoplasms; Maps; Mass Spectrum Analysis; Mediating; Medicine; Methods; Microfluidic Microchips; Mission; Monoclonal Antibodies; Multiplexed Ion Beam Imaging; National Institute of Allergy and Infectious Disease; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Nature; Organ; Paper; Pathogenesis; Pathway interactions; Patients; Peptides; Phase; Pilot Projects; Plasma; Plasmablast; Population; Procedures; Process; Protein Array; Proteins; Proteomics; Reagent; Receptor Cell; Receptors, Antigen, B-Cell; Regulator Genes; Regulatory Pathway; Research; Research Personnel; Rheumatism; Rheumatoid Arthritis; Sample Size; Sampling; Signal Pathway; Signaling Molecule; Skin; Study Subject; Synovial Membrane; Systemic Lupus Erythematosus; Systems Biology; T-Cell Receptor; T-Lymphocyte; T-Lymphocyte Subsets; T-cell receptor repertoire; Techniques; Technology; Tissue Sample; Tissues; Toll-like receptors; Transcript; Transposase; Universities; Validation; Yeasts; adaptive immune response; arm; base; cellular imaging; chemokine; comparative; cytokine; epigenomics; human subject; innovation; keratinocyte; kidney cell; monocyte; new technology; new therapeutic target; novel; novel marker; patient population; programs; public health relevance; receptor; recruit; repository; response; single cell analysis; single-cell RNA sequencing; statistical center; therapeutic target; tissue biomarkers; transcription factor; transcriptome sequencing; transcriptomics; virome

 DESCRIPTION (provided by applicant): The broad, long term objective of the Stanford Technology Accelerating Medicines Partnership (STAMP) Center is to serve as the leader within the RA/SLE AMP Network in the development and implementation of multiplexed mechanistic assays for AMP studies. Although we propose to focus on SLE, our methods will be used in pilot studies for RA and can be applied to any autoimmune disease. Investigators participating in this AMP proposal, and other collaborators at Stanford, have been leading innovators in the development of high-throughput genomics and proteomics technologies for studying cancer and autoimmunity. Project 1 (Steve Quake and Howard Chang) will perform transcript profiling using RNA-Seq of single cells isolated from tissue samples and blood, then separating into individual wells using Fluidigm-based microfluidics devices (C1) or FACS. The Chang lab will determine binding of transcription factors to open chromatin, repressing and/or activating transcriptional programs involving NFAT, NF¿B, RORs, IRFs, STATs, and other transcription factors. Project 2 (Garry Nolan) will employ CyTOF to study cells obtained from blood and tissue, characterizing cell surface molecules, signaling molecules, and phospho-specific epitopes in discrete cellular subsets. Upregulated transcripts from Project 1 will inform selection of CyTOF antibodies in an iterative process during the UH3 funding period. Project 3 (Bill Robinson, Mark Davis and PJ Utz) will use autoantibody profiling, FACS, repertoire-sequencing and yeast display to characterize antigen- specific B and T cells in blood and isolated from tissues. The Robinson and Davis labs will characterize the B and T cell receptor repertoire by sequencing heavy and light chain genes from FACS sorted plasmablasts, and FACS or tetramer sorted T cells, as well as cells isolated from tissue. Monoclonal antibodies will be cloned, expressed, and purified for antigen identification. Antigen targets will be discovered (Utz and Robinson) using protein arrays, which will serve as a core assay for all AMP Network Centers. Pilot projects are also proposed including plasma virome sequencing and two projects to develop and implement multiplexed ion beam imaging (MIBI). Finally, to insure availability of blood, kidney, skin, and synovium for our studies, subjects will be recruited from Stanford and the Bay Area (SLE); UCLA and Cedars- Sinai (SLE); and UCSD (RA), as well as from other AMP Centers. Integration of all assays at one AMP Center will facilitate discovery of pathways, molecules, and new drug targets.

 描述（由应用程序提供）：斯坦福技术加速药物合作伙伴关系（Stamp）中心的广泛，长期目标是在开发和实施AMP研究的多重机械测定法中作为RA/SLE AMP网络中的领导者。尽管我们建议专注于SLE，但我们的方法将用于RA的试点研究，并可以应用于任何自身免疫性疾病。参与该AMP提案的研究人员以及斯坦福大学的其他合作者一直领先于开发用于研究癌症和自身免疫性的高通量基因组学和蛋白质组学技术。项目1（Steve Quake and Howard Chang）将使用从组织样品和血液中分离出的单细胞的RNA-Seq进行笔录分析，然后使用基于流体的微流体设备（C1）或FACS分离为单个井分成单个井。 Chang Lab将确定转录因子与打开染色质，反映和/或激活涉及NFAT，NF¿B，RORS，IRFS，Stats和其他转录因子的转录程序的结合。项目2（Garry Nolan）将采用细胞来研究从血液和组织获得的细胞，表征细胞表面分子，信号传导分子和磷酸特异性表位的细胞。项目1的上调笔录将在UH3融资期间在迭代过程中为细胞抗体的选择提供信息。项目3（Bill Robinson，Mark Davis和PJ UTZ）将使用自身抗体分析，FACS，曲目测序和酵母显示，以表征血液中的抗原特异性B和T细胞，并与组织分离出来。罗宾逊和戴维斯实验室将通过对facs排序的静脉曲张，FACS或四聚体排序的T细胞以及与组织分离的细胞进行测序，通过对FACS排序的重链基因进行测序，来表征B和T细胞受体库。将使用蛋白质阵列发现单克隆抗体抗原靶标（UTZ和Robinson），这将作为所有AMP网络中心的核心测定法。还提出了试点项目，包括血浆病毒蛋白测序和两个开发和实施多路复用离子束成像（MIBI）的项目。最后，为了确保我们的研究的血液，肾脏，皮肤和滑膜的可用性，将从斯坦福大学和海湾地区（SLE）招募受试者； UCLA和CEDARS-SINAI（SLE）；和UCSD（RA）以及其他AMP中心。在一个放大器中心的所有测定中的整合将有助于发现途径，分子和新药物靶标。

项目成果

T Cell-Dependent Affinity Maturation and Innate Immune Pathways Differentially Drive Autoreactive B Cell Responses in Rheumatoid Arthritis.

• DOI: 10.1002/art.40578
• 发表时间: 2018-11
• 期刊: Arthritis & rheumatology (Hoboken, N.J.)
• 作者: Lu DR;McDavid AN;Kongpachith S;Lingampalli N;Glanville J;Ju CH;Gottardo R;Robinson WH
• 通讯作者: Robinson WH

A Comprehensive Atlas of Immunological Differences Between Humans, Mice, and Non-Human Primates.

• DOI: 10.3389/fimmu.2022.867015
• 发表时间: 2022
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Bjornson-Hooper ZB;Fragiadakis GK;Spitzer MH;Chen H;Madhireddy D;Hu K;Lundsten K;McIlwain DR;Nolan GP
• 通讯作者: Nolan GP

Variation of Immune Cell Responses in Humans Reveals Sex-Specific Coordinated Signaling Across Cell Types.

• DOI: 10.3389/fimmu.2022.867016
• 发表时间: 2022
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Fragiadakis GK;Bjornson-Hooper ZB;Madhireddy D;Sachs K;Chen H;McIlwain DR;Spitzer MH;Bendall SC;Nolan GP
• 通讯作者: Nolan GP