权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Next-generation ligandomics technology to globally map cellular ligands of the retina

下一代配体组学技术可全局绘制视网膜细胞配体图谱

基本信息

批准号：
10081460
负责人：
Hong Tian
金额：
$ 22.63万
依托单位：
LIGANDOMICSRX, LLC
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10081460
关键词：
Address Angiogenic Factor Antibody Therapy Autocrine Communication Binding Biomedical Research Cell Communication Cell membrane Cell surface Cells Cellular biology Complex DNA sequencing Data Detection Development Diabetes Mellitus Disease Drug Targeting Endothelial Cells Endothelium Event FDA approved Generations Homeostasis Human Individual Intellectual Property Ligand Binding Ligands Location Maps Mediating Methods Mus Organism Paracrine Communication Pathogenicity Pharmaceutical Preparations Phase Positioning Attribute Proteins Proteome Proteomics Reporting Research Retina Role Running Safety Signal Pathway Signal Transduction Small Business Innovation Research Grant Source Technology Therapeutic Therapeutic Intervention Tissues Transcript Transmembrane Domain Vascular Endothelial Cell Vision research autocrine base case-by-case basis cell type comparative diabetic drug discovery drug quality effective intervention extracellular improved innovation innovative technologies mouse model neutralizing monoclonal antibodies new technology next generation novel novel therapeutics paracrine protein expression protein profiling receptor side effect single-cell RNA sequencing targeted treatment therapeutic target transcriptome transcriptomics

项目摘要

Project Summary Extracellular ligands are among the most valuable drug targets, but are much less exploited for disease therapy than plasma membrane receptors. This is mainly because the technical hurdles for ligand discovery are much greater than those for receptors, the latter of which can be conveniently identified based on their transmembrane domains. Current omics technologies, such as proteomics, functional proteomics and transcriptomics, are not designed to map extracellular ligands. Consequently, extracellular ligands are traditionally identified and characterized on a case-by-case basis with inherent technical challenges. It is even more daunting to delineate ligands with therapeutic potential. To address these challenges, we recently developed a unique platform technology of ligandomics for global mapping of cell-wide ligands as well as disease-selective ligands in the absence of receptor information. The validity and utility of this innovative technology has been demonstrated by efficient discovery of highly disease-selective angiogenic factors and rapid development of novel anti-angiogenic therapies with high efficacy and minimal side effects on normal vessels. However, this first-generation ligandomics technology has the limited application only to homogeneous cells. In this project, we will develop next-generation ligandomics technology that is applicable to any type of cells. In Aim 1, we will develop the next- generation ligandomics technology to map ligand-secreting and binding cells connected through different ligand signaling pathways. In Aim 2, we will apply the new technology to diabetic and healthy retina to systematically identify diabetes-selective cellular ligands. The successful implementation of this project will markedly improve the capacity of ligandomics to identify cellular ligands and disease-selective ligands for different cells. Our new ligandomics technology developed in this project is universally applicable to any cells, tissues and diseases, and therefore may have the potential to impact on a broad field of cell biology research and drug target discovery.

项目摘要细胞外配体是最有价值的药物靶点之一，但很少用于疾病治疗而不是质膜受体。这主要是因为配体发现的技术障碍要大得多后者可以基于它们的跨膜结构域方便地鉴定。目前的组学技术，如蛋白质组学、功能蛋白质组学和转录组学，并不是为了绘制细胞外配体。因此，细胞外配体传统上是在细胞外基质上鉴定和表征的。具体情况具体分析，但存在固有的技术挑战。更令人生畏的是，治疗潜力为了应对这些挑战，我们最近开发了一种独特的平台技术，用于在不存在配体的情况下对全细胞配体以及疾病选择性配体进行全局定位的配体组学受体信息这项创新技术的有效性和实用性已被证明是有效的高度疾病选择性血管生成因子的发现和新型抗血管生成药物的快速开发这些疗法具有高疗效和对正常血管的最小副作用。然而，这第一代配体组学技术仅对同质细胞具有有限的应用。在这个项目中，我们将开发适用于任何类型细胞的下一代配体组技术。在目标1中，我们将开发下一个- 通过不同配体连接的配体分泌和结合细胞的生成配体组学技术信号通路在目标2中，我们将把新技术应用于糖尿病和健康视网膜，鉴定糖尿病选择性细胞配体。该项目的成功实施将显著改善配体组学鉴定不同细胞的细胞配体和疾病选择性配体的能力。我们的新本项目开发的配体组学技术普遍适用于任何细胞、组织和疾病，因此可能对细胞生物学研究和药物靶点发现的广泛领域产生影响。