Project 1

Temporomandibular disorders (TMDs) encompass a group of complex conditions predominantly affecting women, characterized by diverse causes and clinical presentations that significantly reduce quality of life through limitations in jaw function, head and neck pain, sleep disturbances, and psychological distress, thereby impacting daily activities, work productivity, and social interactions. Evidence from clinical, behavioral, and biological studies indicates that TMDs involve multisystem disruptions, including overlaps with chronic pain conditions, heightened psychological distress, poor sleep quality, biomechanical joint and muscle alterations, autonomic nervous system dysregulation, differential DNA methylation patterns, altered inflammatory markers, and brain changes associated with pain processing and therapeutic responses. Despite these insights, the clinical variability of TMDs hinders effective prognosis and individualized interventions, necessitating comprehensive phenotyping to identify reproducible subtypes and facilitate targeted therapies. Our project aims to establish a national, interdisciplinary, patient-centered research infrastructure through CREATE, a collaborative network leveraging resources and expertise across multiple institutions to conduct a large-scale, multi-site clinical study. This initiative includes characterizing diverse TMD cohorts through clinical and behavioral measures (Aim 1), identifying biomarkers linked to distinct phenotypes (Aim 2), tracking longitudinal changes to predict trajectories and outcomes (Aim 3), and developing clinically informed preclinical models to establish causal mechanisms and optimize diagnostics and treatments (Aim 4). The study will utilize advanced data analytics, including traditional and AI-driven approaches, to analyze data collected over two years, incorporating biomarkers, ecological momentary assessments, and wearable device metrics to refine phenotypic classifications. Access to existing datasets such as OPPERA, BACPAC, and RE- JOIN will enable validation and replication of findings, supporting the development of targeted prevention and intervention strategies. Ultimately, this collaborative effort, integrated with the Bioinformatics and Data Science Core and aligned with stakeholder needs, seeks to transform TMD care by enhancing diagnostics, improving treatment precision, and reducing the burden of these complex disorders, offering substantial benefits for patients and advancing the field of TMD research and clinical practice.