PROJECT SUMMARY Approximately 35 million people in the United States are affected by temporomandibular disorders (TMDs) with women 3-8 times more likely to seek treatment compared to men, making it a highly prevalent and expensive healthcare challenge demanding immediate attention. Identifying a specific and treatable cause for TMD is difficult, as it is caused by complex, multifaceted interactions involving biomechanical, biological, and psychosocial components that are poorly understood. Due to these significant gaps in knowledge and the limited integrated mechanistic understanding of TMD, successful long-term therapeutic approaches and patient-specific guidelines to treatment are not available. Our proposal, TMJ SYMPHONY: Systems-integrated model and mechanisms of patient-centered holistic outcomes and network-supported training and therapy, will strategically coalesce a multidisciplinary and multiscale national consortium to decipher the relationships between temporomandibular joint (TMJ) structure-function-pain using computational, cellular, animal and human models. This collective of talented investigators will build upon an existing MPI U01 focused on healthy TMJ structure- function between intramural NIDCR Clinical Researchers and extramural Basic Scientists. It will leverage existing national resources (e.g. RE-JOIN, OPPERA, DOCTRC) to accelerate the translation of discoveries and technologies to directly address TMJ disease diagnosis (e.g., multimodality deep phenotyping, biomarkers), the spectrum of healthy TMJ to preclinical TMJ disease to TMJ degeneration/pain, treatment (e.g., non-invasive holistic/conservative therapies, stem cell therapy, tissue engineered constructs), and improve outcome assessment by understanding patient adaptive capabilities, mind-body-TMJ connection and environmental impact on behavior and perception, and social determinants of TMJ health/disease in a diverse patient population. In this planning phase, we will strategize to make dramatic progress in mechanistic knowledge and identifying combinatorial etiology, while expanding care options, providing evidence-based treatment decisions, and patient-specific treatment modalities over the next decade. What justifies our optimism are our new approaches and techniques already in progress (e.g. chair-side TMJ structure-function-pain assessment toolkit and deep clinical phenotyping, TMJ omics, multi-modality data driven models) and the enthusiasm of clinicians and researchers alike to harness their expertise to identify clinical deliverables to prevent, treat or cure this compelling and complex disorder. The successful completion of the following aims of this planning grant will hone our vision in tackling the TMD IMPACT challenge: (1) Organize, coordinate, and build an integrated multi- disciplinary consortium to mechanistically understand TMJ health and disease, (2) Adapt existing scientific and clinical centers and establish an administrative core which are integrated and focused on TMJ health and disease research, (3) Develop clinical protocols, multi-site clinical research and trials network, and (4) Develop a research training and education program that fosters interdisciplinary career development.

PROJECT NARRATIVE Temporomandibular Disorders (TMDs) are prevalent and expensive healthcare challenges with complex multifaceted etiology in which currently limited integrated mechanistic understanding prevents development of successful long-term therapeutic approaches and patient-specific guidelines to treatment. Our proposal, TMJ SYMPHONY: Systems-integrated model and mechanisms of patient-centered holistic outcomes and network- supported training and therapy, will strategically coalesce a multidisciplinary and multiscale national consortium to decipher the relationships between temporomandibular joint (TMJ) structure-function-pain using computational, cellular, animal and human models. In this planning phase, we will strategize to hone our vision in tackling the TMD IMPACT challenge with the goal to make dramatic progress in mechanistic knowledge and identifying combinatorial etiology, while expanding care options, providing evidence-based treatment decisions and patient-specific treatment modalities, and develop innovative interdisciplinary training over the next decade.