Micro-TeACH (Microbiome Technology and Analytic Center Hub)

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.