Micro-TeACH (Microbiome Technology and Analytic Center Hub)

Micro-TeACH（微生物组技术和分析中心中心）

基本信息

批准号：
10452190
负责人：
Jose C Clemente
金额：
$ 65万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-03-10 至 2026-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10452190
关键词：
Address Affect Atopic Dermatitis Autoimmune Biological Assay Biological Markers Biological Response Modifier Therapy Biopsy Biopsy Specimen Cell Communication Cells Clinical Collaborations Communities Computer software Cues Custom Data Dermatology Development Disease Disease Pathway Drug toxicity Environmental Risk Factor Event Foundations Fungal Genes Gene Expression Profiling Genetic Goals Growth Heterogeneity High-Throughput Nucleotide Sequencing Human Human Microbiome Immune Immunoglobulin A Immunomodulators Individual Differences Inflammation Inflammatory Inflammatory Bowel Diseases Inflammatory Response Intervention Investigation Knowledge Portal Lesion Link Lupus Malignant Neoplasms Mediating Metadata Metagenomics Methods Methotrexate Microbe Molecular Mus Onset of illness Oral cavity Oral mucous membrane structure Outcome Pathogenesis Pathway interactions Patients Pharmaceutical Preparations Phase Phenotype Prediction of Response to Therapy Psoriasis Psoriatic Arthritis Publications Quality of life Research Personnel Resolution Resources Rheumatoid Arthritis Rheumatology Ribosomal RNA Role Salivary Glands Sampling Shotguns Site Sjogren&apos s Syndrome Skin Skin Tissue Surface Systemic Lupus Erythematosus Systems Biology Technology Therapeutic Tissue Banks Tissues Variant Work autoimmune pathogenesis base clinical phenotype cohort disease heterogeneity drug metabolism drug response prediction dysbiosis early onset experience field study gut microbiome high dimensionality immune activation insight interest medical schools metagenome metatranscriptomics microbial microbial composition microbial disease microbiome microbiome analysis microbiome research microbiota microorganism multidisciplinary new technology novel oral microbiome oral tissue precision medicine predictive modeling predictive tools programs reconstruction responders and non-responders response rheumatologist single-cell RNA sequencing skin microbiome transcriptome transcriptomics treatment response

项目摘要

ABSTRACT Despite many advances in the field, the pathogenesis of autoimmune and immune-mediated diseases (AIMDs) remains incompletely understood but appears to be multifactorial; genetic and environmental factors are implicated in the aberrant inflammatory responses in many AIMDs, including lupus, rheumatoid arthritis (RA), psoriatic spectrum diseases (PSD) and Sjogren’s syndrome (SS). Among potential triggers for these disorders is the human microbiome, the communities of microorganisms that inhabit most body sites and surfaces. Perturbations in the the skin, oral and gut microbiome are known to induce host immune cell activation, downstream inflammation, and persistent tissue damage, contributing to the development of various AIMDs. The last three decades have also witnessed fundamental advances in AIMD therapeutics. For example, the use of methotrexate and subsequent incorporation of biologic treatments has led to substantial improvements in RA and PSD clinical outcomes, enhancing the quality of life for millions of patients. However, despite this progress a significant question remains unanswered: why do over 50% of patients with moderate to severe disease fail to respond appropriately to these agents? Pharmacomicrobiomics – an emerging field of study that investigates the effects of variations of the human gut microbiome on drugs – promises to overcome these barriers and facilitate precision medicine approaches in AIMDs. Further, studying the microbiome in the context of the AMP-AIM Network’s goal of disease reconstruction through high dimensional analytics of tissue biopsies and samples will create a unique opportunity to incorporate potential triggers of immune activation and predictors of drug response. With a multidisciplinary team composed of computational biologists, rheumatologists, geneticists, and microbiome researchers, we propose the creation of Micro-TeACH (Microbiome Technology and Analytic Center Hub), a formal expansion of a longstanding NYC-based collaboration between Drs. Scher, Heguy (NYU Grossman School of Medicine) and Clemente (Mount Sinai School of Medicine) that will integrate expertise in AIMDs (RA, PSD and inflammatory bowel disease), extensive and well-phenotyped biosamples, and state-of- the-art microbiomics methods to AMP AIM with the ultimate goals of: 1) identifying microbes and microbial pathways as potential determinants of disease pathogenesis; 2) interrogating host-microbe spatial interactions in affected tissues; and 3) discovering microbiome-based precision medicine approaches. To achieve these goals, we will utilize the unique resources available to our groups and integrate our software pipelines, microbiomics expertise, and data/metadata with biosamples and data accrued by all AMP AIM Disease Teams, Technology and Analytic Cores, System Biology Cores and Knowledge Portal. This approach should elevate the overarching aim of the AMP AIM Program, which seeks to gain a comprehensive understanding of molecular and cellular disease pathways and to identify novel targets for intervention.

抽象的尽管该领域取得了许多进步，但自身免疫性和免疫介导的探测的发病机理（AIMD）仍然不满意的是Buta似乎是多因素的；在许多AIMD中与异常炎症反应有关，包括狼疮，类风湿关节炎（RA），银屑病频谱疾病（PSD）和Sjogren综合征（SS）。是人类微生物组，是大多数身体部位和表面的微生物群落。皮肤中的扰动，口服和肠道微生物组已知会激活，下游炎症和持续的组织损伤，有助于各种目标的发展。过去的三十年还见证了AIMD治疗的基本进步。使用甲氨蝶呤和随后掺入生物治疗已导致实质性改善在RA和PSD临床结果中，可以提高数百万患者的生活质量。进展一个重大问题仍未得到解决：为什么超过50％的中度至重度患者疾病无法反应这些药物吗？研究人类肠道微波经对药物的变化的影响 - 有望克服这些障碍和促进精度医学进一步研究。 AMP-AIM网络通过高高高高高高CET进行疾病重建目标的背景组织活检和样品将建立独特的机会，以结合免疫激活的潜在触发器和药物反应的预测因素。由综合学家，风湿病学家，遗传学家和一个多学科团队组成微生物组研究人员，我们提出了微技术的创建（微生物组技术和分析 Center Hub），这是一个长期以来基于纽约市的合作的正式扩展。 Grossman医学院和克莱门特（西奈山医学院），将整合专业知识 AIMDS（RA，PSD和炎症肠疾病），广泛且良好的生物样品以及最佳状态 ART微生物学方法的AMP瞄准以下最终目标：1）识别微生物和微生物作为疾病发病机理的潜在决定因素； 2）受影响组织的相互作用； 3）发现基于微生物组的精确药物方法。为了实现目标，我们将利用我们团体可用的独特资源并整合我们的软件管道，微生物学专业知识和数据/元数据，具有生物样本和所有放大器的数据瞄准疾病团队，技术和分析核心，系统生物学核心和知识门户方法shoud提升了AMP AIM计划的总体目标，该计划试图获得补偿性了解分子和细胞疾病途径，并确定国际的新目标。