The spectrum of conditions known as Temporomandibular Joint Disorders and Orofacial Pain (TMJD/OP) are difficult to diagnose and manage because their etiologies and pathogeneses are poorly understood. Progress towards definitive therapies and rational diagnoses has been slow due to the complex nature of the disorders and the lack of scholars working in this field, many of whom utilize a very narrow """"""""silo"""""""" approach to investigating these disorders. We propose training four high caliber clinician scientists and basic scientists per year to enhance the number and quality of interdisciplinary researchers that can appropriately unravel the mechanisms underlying TMJD/OP and identify the most effective treatments. Towards this objective, we will engage Scholars for interdisciplinary mentorship in TMJD/OP, with the goal of bridging bench to bedside and back, to better understand these conditions in three main areas of inquiry: (1) pain mechanisms and therapies;(2) TMJ pathogenesis;and (3) developmental biology, regeneration and tissue engineering of joint, muscle and ligaments. Where appropriate, embedded within each of these areas will be research and didactic experiences in contemporary methodologies, including bioinformatics, genomics, imaging and biomarkers. The Scholars will have a minimum of 75 percent protected time for research and research career development. An individualized career development plan will be customized with each scholar and their interdisciplinary research mentors and mentorship team. Each plan will include an intensive supervised research experience, didactic training including instruction and assistance in grant writing/submission and scientific writing, ongoing mentor feedback, formal annual evaluation, and instruction in the responsible conduct of research. The Scholars'mentoring teams, didactic coursework, and experiential learning will highlight the need to understand the entire translational continuum and the complex interplay between """"""""peripheral"""""""" and """"""""central"""""""" factors that contribute to complex chronic pain states. The training of interdisciplinary scholars under the mentorship of established investigators, including those working in related areas outside the field, will likely lead to novel discoveries and provide the needed momentum for innovations in the diagnostics and therapeutics for TMJD/OP. These include: 1) the ability to better """"""""phenotype"""""""" these patients to identify sub-sets of individuals (i.e. endophenotypes) that respond to specific therapies;2) th identification and use of local or systemic biomarkers to diagnose disease or monitor improvements in therapy;3) the use of both """"""""peripheral"""""""" and central nervous system, joint and muscle imaging technologies for earlier and more sensitive diagnostics;and 4) the use of biomedicine, biomimetics, and imaging to design and manufacture bioengineered joints. Collectively, this application offers a comprehensive and systems-based approach to training researchers in the TMJD/OP field.

Public Health Relevance

TMJD and OP comprise a poorly understood spectrum of disorders that negatively impact eating, speech and facial functions, and are a substantial health burden in the United States. Scientific advances in molecular biology, genetics, imaging, biomarkers, and computational biology offer novel approaches to better understand these disorders. We propose assembling a unique interdisciplinary mentorship program to train the next generation of high caliber TMJD/OP investigators with the goal of enhancing the quality and specificity of patient care.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Physician Scientist Award (Program) (PSA) (K12)
Project #
5K12DE023574-02
Application #
8691783
Study Section
Special Emphasis Panel (ZDE1)
Program Officer
King, Lynn M
Project Start
2013-07-01
Project End
2018-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Dentistry
Type
Schools of Dentistry/Oral Hygn
DUNS #
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Ge, Chunxi; Zhao, Guisheng; Li, BinBin et al. (2018) Genetic inhibition of PPAR? S112 phosphorylation reduces bone formation and stimulates marrow adipogenesis. Bone 107:1-9
Ge, C; Mohamed, F; Binrayes, A et al. (2018) Selective Role of Discoidin Domain Receptor 2 in Murine Temporomandibular Joint Development and Aging. J Dent Res 97:321-328
Harper, Daniel E; Ichesco, Eric; Schrepf, Andrew et al. (2018) Relationships between brain metabolite levels, functional connectivity, and negative mood in urologic chronic pelvic pain syndrome patients compared to controls: A MAPP research network study. Neuroimage Clin 17:570-578
Harper, D E; Hollins, M (2017) Conditioned pain modulation dampens the thermal grill illusion. Eur J Pain 21:1591-1601
Li, Yan; Ge, Chunxi; Franceschi, Renny T (2017) MAP Kinase-Dependent RUNX2 Phosphorylation Is Necessary for Epigenetic Modification of Chromatin During Osteoblast Differentiation. J Cell Physiol 232:2427-2435
Cao, H; Alrejaye, N; Klein, O D et al. (2017) A review of craniofacial and dental findings of the RASopathies. Orthod Craniofac Res 20 Suppl 1:32-38
Wu, Biming; Durisin, Emily K; Decker, Joseph T et al. (2017) Phosphate regulates chondrogenesis in a biphasic and maturation-dependent manner. Differentiation 95:54-62
Schrepf, Andrew; Harte, Steven E; Miller, Nicole et al. (2017) Improvement in the Spatial Distribution of Pain, Somatic Symptoms, and Depression After a Weight Loss Intervention. J Pain 18:1542-1550
Harper, Daniel E; Shah, Yash; Ichesco, Eric et al. (2016) Multivariate classification of pain-evoked brain activity in temporomandibular disorder. Pain Rep 1:
Ge, Chunxi; Cawthorn, William P; Li, Yan et al. (2016) Reciprocal Control of Osteogenic and Adipogenic Differentiation by ERK/MAP Kinase Phosphorylation of Runx2 and PPAR? Transcription Factors. J Cell Physiol 231:587-96

Showing the most recent 10 out of 22 publications