UC2AR081034

Micro-Teach (Microbiome Technology and Analytic Center Hub) - 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 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.

New York University

THE NATIONAL INSTITUTE OF AND MUSCULOSKELETAL AND SKIN DISEASES (NIAMS) MISSION IS TO SUPPORT RESEARCH INTO THE CAUSES, TREATMENT, AND PREVENTION OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES, TRAINING OF BASIC AND CLINICAL SCIENTISTS TO CARRY OUT THIS RESEARCH, AND DISSEMINATION OF INFORMATION ON RESEARCH PROGRESS IN THESE DISEASES. THE EXTRAMURAL PROGRAM PROMOTES AND SUPPORTS BASIC, TRANSLATIONAL, AND CLINICAL STUDIES OF SYSTEMIC RHEUMATIC AND AUTOIMMUNE DISEASES, SKIN BIOLOGY AND DISEASES, BONE BIOLOGY AND DISEASES, MUSCLE BIOLOGY AND DISEASES, AND JOINT BIOLOGY AND DISEASES AND ORTHOPAEDICS. NIAMS SYSTEMIC RHEUMATIC AND AUTOIMMUNE DISEASES PROGRAMS ADDRESS BASIC, TRANSLATIONAL, AND CLINICAL RESEARCH, INCLUDING CLINICAL TRIALS AND OBSERVATIONAL AND MECHANISTIC STUDIES, FOCUSED ON IMMUNE-MEDIATED ARTHRITIS AND AUTOIMMUNE-RELATED ACUTE AND CHRONIC DISORDERS IN ADULTS AND CHILDREN. NIAMS SKIN BIOLOGY AND DISEASES PROGRAMS SUPPORT BASIC, TRANSLATIONAL, AND CLINICAL RESEARCH IN SKIN, INCLUDING BOTH COMMON AND RARE SKIN DISEASES. THESE PROGRAMS INCLUDE INVESTIGATIONS OF THE BASIC MOLECULAR, CELLULAR, AND DEVELOPMENTAL BIOLOGY OF SKIN, AS WELL AS STUDIES OF SKIN AS AN IMMUNE, SENSORY, ENDOCRINE, AND METABOLIC ORGAN. NIAMS BONE BIOLOGY AND DISEASES PROGRAMS SUPPORT RESEARCH ON THE CONTROL OF BONE FORMATION, RESORPTION, AND MINERALIZATION AS WELL AS THE EFFECTS OF SIGNALING MOLECULES ON BONE CELLS. THEY SUPPORT CLINICAL STUDIES OF INTERVENTIONS TO PREVENT FRACTURES ASSOCIATED WITH OSTEOPOROSIS AND RESEARCH INTO LESS COMMON BONE DISEASES. NIAMS MUSCLE BIOLOGY AND DISEASES PROGRAMS ENCOURAGE RESEARCH ON MUSCLE DEVELOPMENTAL BIOLOGY, GROWTH, MAINTENANCE, AND HYPERTROPHY, PHYSIOLOGY OF CONTRACTION, STRUCTURAL BIOLOGY OF THE CONTRACTILE APPARATUS, DISEASE MECHANISMS, BIOMARKERS AND OUTCOME MEASURES, AND DEVELOPMENT AND CLINICAL TESTING OF THERAPIES FOR CONDITIONS INCLUDING THE MUSCULAR DYSTROPHIES. NIAMS JOINT BIOLOGY, DISEASES, AND ORTHOPAEDICS PROGRAMS SUPPORT A BROAD SPECTRUM OF RESEARCH CENTERED ON THE INTERPLAY AMONG THE BODY'S MUSCLES, BONES, AND CONNECTIVE TISSUES. THEY ENCOURAGE TISSUE ENGINEERING AND REGENERATIVE MEDICINE RESEARCH, MOLECULAR BIOLOGY, IMAGING, AND CLINICAL RESEARCH, AND THE TREATMENT AND PREVENTION OF ORTHOPAEDIC CONDITIONS. NIAMS PARTICIPATES IN THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) AND SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAMS. THE SBIR PROGRAM IS INTENDED TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE STTR PROGRAM IS INTENDED TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.867 - Vision Research

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [HHS - NIH]

National Eye Institute (NEI) [HHS - NIH]

New York United States

State-Wide

Accelerating Medicines Partnership Autoimmune and Immune-Mediated Diseases: Technology and Analytic Cores (TACs) and Research Management Unit (RMU) (UC2 Clinical Trial Not Allowed) (RFA-AR-21-016)

Amendment Since initial award the total obligations have increased 557% from $350,000 to $2,298,342.