Project Grant R21AR084036

THE EXPOSOME IN RHEUMATOID ARTHRITIS AND SYSTEMIC LUPUS ERYTHEMATOSUS: EXACT NETWORK PLANNING - PROJECT SUMMARY THIS IS AN EXPLORATORY DEVELOPMENTAL GRANT AIMED AT THE DESIGN, DEVELOPMENT, AND IMPLEMENTATION OF A FUTURE NATIONAL, INTERDISCIPLINARY, COLLABORATIVE, TEAM SCIENCE RESEARCH NETWORK THAT WILL ADVANCE THE STUDY OF THE EXPOSOME IN AUTOIMMUNE DISEASES (EXPOSOME IN AUTOIMMUNE DISEASES COLLABORATING TEAMS, EXACT). WE PROPOSE TO PLAN A STUDY OF THE EXPOSOME DURING THE PRE-CLINICAL PERIOD OF RHEUMATOID ARTHRITIS (RA) AND SYSTEMIC LUPUS ERYTHEMATOSUS (SLE). WE ASSERT THAT IT IS IMPORTANT TO MEASURE THE EXPOSOME PRIOR TO THE DEVELOPMENT OF DISEASE TO ENSURE THAT WHAT WE ARE MEASURING PRECEDES THE DISEASE AND IS NOT A CONSEQUENCE OF THE DISEASE (WHICH MIGHT HAPPEN IF THE EXPOSOME WERE MEASURED IN DISEASED INDIVIDUALS). THIS WILL ALLOW US TO DRAW INFERENCE ABOUT THE TEMPORALITY AND POTENTIAL CAUSALITY OF EXPOSURES ON THE RISK OF RA AND SLE. THIS CAN BE ACCOMPLISHED USING PROSPECTIVE COHORTS OF AT-RISK INDIVIDUALS THAT ARE FOLLOWED FOR THE DEVELOPMENT OF CLINICAL DISEASE (IE CLASSIFIABLE RA AND SLE) WITH WHICH WE HAVE A LONG HISTORY OF WORKING. INVESTIGATORS AT THE UNIVERSITY OF COLORADO ANSCHUTZ MEDICAL CAMPUS (NORRIS, HOLERS AND ABRAHAM) WILL WORK WITH INVESTIGATORS AT THE OKLAHOMA MEDICAL RESEARCH FOUNDATION (JAMES AND MUNROE) TO CONDUCT A LANDSCAPE ANALYSIS OF RELEVANT EXISTING 1) RESOURCES, POPULATIONS, DATABASES, REGISTRIES, REPOSITORIES AND CONSORTIA, 2) DATA ON RELEVANT EXPOSURES, 3) EXPOSOME LABORATORIES, AND 4) EXPOSOME ANALYTIC TECHNIQUES. THIS WILL PROVIDE A BACKGROUND THAT WE WILL USE TO PLAN ACTIVITIES FOR A NEW PROJECT TO STUDY THE EXPOSOME IN RA AND SLE. AS PART OF THE PLANNING PROCESS, WE WILL HOLD A SUMMIT OF EXPOSOME EXPERTS AND INVESTIGATORS WITH COHORTS/POPULATIONS OF INDIVIDUALS AT-RISK FOR RA AND SLE, TO DEVELOP AND EXPAND EXISTING RESEARCH COLLABORATIONS TO CONDUCT A PROSPECTIVE STUDY IN THE EXPOSOME OF THESE DISEASES. WE WILL USE OUR EXISTING NOVEL COHORTS OF AT-RISK INDIVIDUALS WHO HAVE BEEN FOLLOWED TO THE DEVELOPMENT OF CLASSIFIABLE RA AND SLE TO EXPLORE FEASIBILITY OF HARMONIZATION OF QUESTIONNAIRE AND BIOMARKER DATA AND CONDUCT SECONDARY DATA ANALYSIS TO SUPPORT THE HYPOTHESIS AND RESEARCH STRATEGY OF THE FUTURE EXACT NETWORK. WE WILL ENGAGE STAKEHOLDERS SUCH AS SCIENTIFIC OR PROFESSIONAL ASSOCIATIONS AND PATIENTS AND PATIENT-ADVOCATES IN THE AREAS OF RA AND SLE FOR BETTER TRANSLATION TO INFORM THE EXACT NETWORK RESEARCH AGENDA. THE OVERALL GOAL OF THIS PROPOSAL IS TO PLAN RESEARCH STRATEGIES AND DEVELOP PARTNERSHIPS, INFRASTRUCTURE, AND CAPABILITIES NEEDED TO ADDRESS THE MAJOR GOALS OF A FUTURE COLLABORATIVE EXACT NETWORK AND TO DEVELOP A RESEARCH FRAMEWORK AND STRATEGIES TO SUPPORT COORDINATION AMONG STUDIES, COLLABORATIVE RESEARCH PROJECTS, AND SITES. SPECIFIC AIM 1. TO CONDUCT A MULTIPRONGED APPROACH TO DETERMINE THE NEEDS AND CURRENTLY AVAILABLE RESOURCES TO PROSPECTIVELY AND EFFECTIVELY MEASURE THE EXPOSOME IN RA AND SLE (VIA A LANDSCAPE ANALYSIS). SPECIFIC AIM 2. TO DESIGN A PROSPECTIVE STUDY TO EXAMINE THE ROLE OF THE EXPOSOME IN THE ETIOLOGY OF RA AND SLE, WITH AN INTERDISCIPLINARY RESEARCH TEAM, RIGOROUS EXPOSOME MEASUREMENTS AND NOVEL ANALYTIC APPROACHES.