Grants

Currently active awards to CCMB faculty

USC Facebase IV Craniofacial Development and Dysmorpholoy Data Management and Integration Hub (FaceBase IV) – Grant #U24 DE034163

  • Principal Investigator: Carl Kesselman, PhD, and Yang Chai, DDS, PhD
  • Sponsor: National Institutes of Health
  • Period: 08/15/2024-05/31/2029
  • Goal: The major goal of the FaceBase data resource is to advance the impact of research into Dental, Oral and Craniofacial health and disease on improving human health. We will accomplish this by expanding the scope and scale of the existing FaceBase data repository resource to include research across all of DOC research and across the translational spectrum, from basic research to clinical applications.

Center for TMD IMPACT – Grant # R34 DE033572

  • Principal Investigator: Yang Chai, DDS, PhD, and Jianfu Chen, PhD
  • Sponsor: NIH
  • Period: 09/19/2023-09/18/2025
  • Goal: To assemble a comprehensive multi-institutional Center for TMD Improving Patient-Centered Translational Research (C-TMD IMPACT) including clinicians, research scientists, regulatory experts, and clinical trial specialists to advance basic and clinical research, research training, and evidence-based treatment for TMDs.

Alpha Clinic Network Expansion for Cell and Gene Therapies – Grant # INFR4-13878

  • Principal Investigator: Tom Buchanan PhD, Co-Investigator: Yang Chai, DDS, PhD
  • Sponsor: CIRM
  • Period: 02/01/2023-01/31/2028
  • Goal: The AC has a four-part mission to: (a) advance and support clinical trials and therapeutic development for cell and gene therapies; (b) engage diverse and underserved communities in those trials and the resulting therapies; (c) provide training and education to researchers, staff, patients, and communities; and (d) exchange novel expertise with other AC network sites through lead offerings.

Molecular Regulatory Mechanism of Mesenchymal Stem Cells in Adult Mouse Incisors – Grant #R01 DE025221

  • Principal Investigator: Yang Chai, DDS, PhD
  • Sponsor: National Institutes of Health
  • Period: 05/01/2016-12/31/2027
  • Goal: The goal of this project is to provide important knowledge of the signaling network that regulates the transition from MSCs to TA cells in maintaining tissue homeostasis and will serve as the foundation for future studies in MSC biology and stem cell-mediated tissue regeneration.

The Molecular Regulatory Mechanism of Tooth Root Development – Grant #R01 DE022503

  • Principal Investigator: Yang Chai, DDS, PhD
  • Sponsor: National Institutes of Health
  • Period: 07/19/2012-04/30/2029
  • Goal: The major goal of this project is to test the hypothesis that BMPmediated SHH, WNT and FGF signaling and the epigenetic modulator Ezh2 control the fate of epithelial and mesenchymal stem cells during root development.

Center for Dental, Oral and Craniofacial Tissue and Organ Regeneration (C-DOCTOR) – Grant #U24 DE029463

  • Principal Investigator: Yang Chai, DDS, PhD
  • Sponsor: National Institutes of Health
  • Period: 05/07/2020-04/30/2025
  • Goal: The Center for Dental, Oral, & Craniofacial Tissue & Organ Regeneration (C-DOCTOR) is a public-private consortium focused on accelerating promising tissue engineering/regenerative medicine therapies for dental, oral, and craniofacial tissue and organ regeneration to human clinical trials. Our overall vision for C-DOCTOR is to be a comprehensive national resource center for the clinical translation of innovative regenerative technologies to replace DOC tissues or organs lost to congenital disorders, traumatic injuries, diseases, and medical procedures.

Mechanisms and rescue of craniosynostosis associated with gene-environment interaction – Grant #5 R01 DE0030901

  • Principal Investigator: Jianfu Chen, PhD, and Yang Chai, DDS, PhD
  • Sponsor: National Institutes of Health
  • Period: 07/01/2021-04/30/2026
  • Goal: The major goal of this project will improve our understanding of gene-environment interaction in craniosynostosis and guide our therapeutic efforts in MSC-mediated tissue regeneration in treating craniosynostosis.

TGF-β Signaling and Craniofacial Morphogenesis – Grant #R01 DE012711

  • Principal Investigator: Yang Chai, DDS, PhD
  • Sponsor: National Institutes of Health
  • Period: 08/01/2019-07/31/2025
  • Goal: The goal of this project is to understand the molecular and cellular mechanism that is critical for regulating palatal fusion during craniofacial morphogenesis.

Multiplex meningeal lymphatic activation for Alzheimer’s disease – Grant # R21 AG089268

  • Principal Investigator: Jianfu Chen, Ph.D.
  • Sponsor: National Institutes of Health
  • Period: 08/15/2024-05/31/2026
  • Goal: The goal of this project is to establish multiplex brain lymphatic activation strategies as a therapeutic approach for Alzheimer’s disease.

Mapping temporomandibular joint (TMJ) degeneration and pain – Grant # R01 DE033511

  • Principal Investigator: Jianfu Chen, Ph.D.
  • Sponsor: National Institutes of Health
  • Period: 07/01/2024-06/30/2029
  • Goal: This study will establish a high dimensional map of TMJ with or without OA at single cell and 3-D resolutions and validate Netrin-1/Dcc as a new therapeutic target for TMJOA.

MSC implantation as a treatment for developmental brain defects in craniosynostosis – Grant #1 R01 NS136377

  • Principal Investigator: Jianfu Chen, Ph.D.
  • Sponsor: National Institutes of Health
  • Period: 06/01/2024-05/31/2029
  • Goal: This study seeks to provide the preclinical validation of MSC implantation as a better therapeutic strategy over the surgical approach in current clinical practice for brain deficits in craniosynostosis, which is crucial for advances in stem cell-mediated treatment of craniosynostosis.

Brain lymphatic activation for craniosynostosis and Alzheimer’s disease – Grant #1 RF1 NS137467

  • Principal Investigator: Jianfu Chen, Ph.D.
  • Sponsor: National Institutes of Health
  • Period: 06/01/2024-05/31/2027
  • Goal: The goal of this project is to investigate how the brain lymphatic system can be rejuvenated to treat neurological disorders such as craniosynostosis and Alzheimer’s disease (AD).

Center for TMD IMPACT – Grant # R34 DE033572

  • Principal Investigator: Yang Chai, D.D.S., Ph.D., Jianfu Chen, Ph.D.
  • Sponsor: NIH
  • Period: 09/19/2023-09/18/2024
  • Goal: To assemble a comprehensive multi-institutional Center for TMD Improving Patient-Centered Translational Research (C-TMD IMPACT) including clinicians, research scientists, regulatory experts, and clinical trial specialists to advance basic and clinical research, research training, and evidence-based treatment for TMDs.

Neurovascular functions of a small RNA Snord118-mediated ribosome biogenesis – Grant # R21 DE075665

  • Principal Investigator: Jianfu Chen, Ph.D.
  • Sponsor: NIH
  • Period: 02/01/2022-01/31/2024
  • Goal: To establish new genetically modified mice to model small vessel diseases (SVD) and to investigate the function of ribosome biogenesis in neurovascular unit (NVU) cells.

Selective neurovascular regulation by a vascular dementia-related noncoding RNA Snord118 – Grant #1 R21 AG070681

  • Principal Investigator: Jianfu Chen, Ph.D.
  • Sponsor: National Institutes of Health
  • Period: 05/15/2022-04/30/2024
  • Goal: The proposal investigates a small vessel disease caused by mutations in noncoding RNA Snord118, with the goal of improving our understanding of neurovascular biology under pathophysiological conditions.

Mechanisms and rescue of craniosynostosis associated with gene-environment interaction – Grant #5 R01 DE0030901

  • Principal Investigator: Jianfu Chen, Ph.D., Yang Chai, D.D.S., Ph.D.
  • Sponsor: National Institutes of Health
  • Period: 07/01/2021-04/30/2026
  • Goal: The major goal of this project will improve our understanding of gene-environment interaction in craniosynostosis and guide our therapeutic efforts in MSC-mediated tissue regeneration in treating craniosynostosis.

Modeling Pathways of Early Growth Dysregulation at the GEJ – Grant #5 R01 DK135562

  • Principal Investigator: Stephen J Meltzer, Ph.D. and Dechen Lin, Ph.D.
  • Sponsor: National Institutes of Health
  • Period: 05/01/2024 – 02/28/2029
  • Goal: The application will test the hypothesis that dysregulated Platelet Activating Factor (PTAF) and free fatty-acid (FFA) metabolism, via a novel epigenetic crosstalk featuring aberrant HNF4A transcription factor activation, is involved in growth dysregulation and early neoplastic evolution in cardia columnar cells at the human gastroesophageal junction (GEJ-cardia).

Pharmacological and dietary inhibition of a novel metabolic-epigenetic crosstalk in head and neck cancer – Grant #5 R01 CA033648

  • Principal Investigator: Dechen Lin, Ph.D.
  • Sponsor: National Institutes of Health
  • Period: 03/01/2024 – 01/31/2029
  • Goal: Head neck squamous cell carcinoma (HNSCC) is common and aggressive cancer without effective therapy. In this proposal, we will: i) focus on the crosstalk between cancer metabolism and epigenetic regulation to study the primary forces transforming normal oral cells into HNSCC using advanced organoid technology and mouse models; ii) investigate the pharmacological and dietary inhibition of the link between methionine metabolism and epigenetic network.

Development of genome-guided immunotherapeutic strategies for head neck cancer

  • Principal Investigator: Dechen Lin, Ph.D.
  • Sponsor: Ming Hsieh Institute Research Award
  • Period: 08/01/2023 – 08/31/2024
  • Goal: The major goal of this project is to develop MLL3 mutations as biomarkers to predict immunotherapeutic response in patients with head and neck squamous cancer using both animal models and patient-derived tumor organoids.

Master regulator transcription factors promote esophageal neoplastic evolution – Grant #5 R37 CA237022

  • Principal Investigator: Dechen Lin, Ph.D.
  • Sponsor: National Institutes of Health
  • Period: 06/01/2020-05/31/2025
  • Goal: To establish primary driving forces of BE-associated neoplasia evolution and uncover epigenomic mechanisms underlying esophagus transformation, which will fundamentally transform our insights into the biology of esophageal cancer.

Window pre-operative study of FID-007 in patients with squamous cell carcinoma of the head and neck

  • Principal Investigator: Jacob Thomas MD; Co-Principal Investigator: Dechen Lin, Ph.D.
  • Sponsor: Ming Hsieh Institute Research Award
  • Period: 08/01/2023 – 08/31/2024
  • Goal: The major goal of this project is to 1) conduct a clinical trial evaluating the combination of Taxane-based drugs and ICB therapies in HNSCC patients; 2) study the immune-modulating function of Taxane-based drugs using single-cell RNA-seq and patient-derived tumor organoids.

A central regulator and predictive biomarker for head neck cancer immunotherapy

  • Principal Investigator: Uttum Sinha MD, Dechen Lin, Ph.D.
  • Sponsor: The Wright Foundation
  • Period: 08/01/2023 – 07/31/2024
  • Goal: The major goal of this project is to perform single-cell RNA-seq analyses of HNSCC tumor microenvironment to understand the role on STAT1-IFN pathway in anti-tumor immune regulation and to develop biomarkers using multiplexed immunofluorescence of HNSCC tumor samples.

Analyzing the role of cAMP and STAT3 signaling in cartilage homeostasis and osteoarthritis development - Grant # R00 AR077090

  • Principal Investigator: Zhaoyang Liu, Ph.D.
  • Sponsor: National Institutes of Health
  • Period: 03/14/2023-02/28/2026
  • Goal: To utilize mouse genetics, combined with modern genomics and pharmacological approaches, to define the role of cAMP and STAT3 signaling in articular cartilage homeostasis and OA pathogenesis, which may accelerate our diagnosis and treatment of human OA.

Investigating the ADGRG6/GPCR signaling pathway in cartilage homeostasis and musculoskeletal disorders

  • Principal Investigator: Zhaoyang Liu, Ph.D.
  • Sponsor: Herman Ostrow School of Dentistry at USC, Start-up Fund from Provost
  • Period: 06/01/2022-6/01/2025
  • Goal: This proposal investigates the functional role of a G protein-coupled receptor (GPCR) named ADGRG6 in cartilage maintenance and multiple musculoskeletal disorders.

Regulating Skeletal Connectivity in Craniofacial Development and Disease – Grant# 1 R35 DE034346-01

  • Principal Investigator: Amy Merrill, Ph.D.
  • Sponsor: NIH
  • Period: 09/19/2024-06/30/2032
  • Goal: The scope of the proposed study is comprehensive and forward-thinking, as it investigates the craniofacial skeleton as a multi-tissue system, addressing critical gaps in our understanding of craniofacial connective tissue development and maintenance in four complementary research programs.

Role of LGR+ connective tissue progenitors in TMJ development – Grant # R01 DE033893

  • Principal Investigator: Crump, Merrill – multi-PI
  • Sponsor: NIH
  • Period: 07/15/2024-04/30/2029
  • Goal: Disorders of the temporomandibular joint of the jaw are a common source of chronic pain. This proposal uses complementary zebrafish and mouse models to investigate the role of LGRs, which potentiate Wnt signaling, in maintaining and controlling differentiation of stem cells that give rise to diverse jaw joint connective tissues. Knowledge gained from these studies will inform future studies aimed at repairing and restoring damaged connective tissues in temporomandibular joint disease.

Fgf signaling in patterning of the calvarial joints – Grant # 2 R01 DE025222

  • Principal Investigator: Amy Merrill, Ph.D.
  • Sponsor: NIH
  • Period: 07/01/2023-06/30/2028
  • Goal: This study is expected to show that CT fibroblasts are signaling centers that direct calvarial joint development and underlie region-specific fusion patterns in congenital skull deformities.

Developmental regulation of tendon-bone connectivity in the jaw – Grant #5 R01 DE029850

  • Principal Investigator: Amy Merrill-Brugger, Ph.D.
  • Sponsor: National Institutes of Health
  • Period: 06/08/2021-05/31/2026
  • Goal: The major goal of this project is to identify the fundamental steps that regulate development of tendon-bone attachments in the mammalian jaw.

A Peptide-Based Biomineralization Strategy for Tooth Repair – Grant #5 R01 DE027632

  • Principal Investigator: Janet Moradian-Oldak, Ph.D.
  • Sponsor: National Institutes of Health
  • Period: 02/01/2019-01/31/2024
  • Goal: The major goal of this project is to develop a technology that will effectively rebuild dental structures lost due to NCCL lesions and prevent dentin hypersensitivity.

Matrix-Based Mineral (MBM) Enamel Biomimetics – Grant #5 R01 DE13414

  • Principal Investigator: Janet Moradian-Oldak, Ph.D.
  • Sponsor: National Institutes of Health
  • Period: 07/01/2024-04/30/2029
  • Goal: The goal of this proposal is to advance our understanding of ameloblastin’s structure and function through a systematic investigation of its interactions with different targets. The long-term goal is to understand the general principles that apply to the formation of dental enamel and to develop biomimetic strategies for the fabrication of enamel-like materials in-vitro.

Amelogenesis and Ion Transport – Grant #R01 DE029445

  • Principal Investigator: Michael Paine, B.D.S., Ph.D.
  • Sponsor: National Institutes of Health
  • Period: 03/15/2021-02/28/2025
  • Goal: The major goal of this grant is to better define the cellular activities that define the maturation-stage of amelogenesis include calcium, bicarbonate, chloride, proton and phosphate transport, and the strict control of intracellular and extracellular pH. This project seeks to understand cellular activities that regulate and maintain an enamel extracellular matrix pH conducive to enamel mineralization.

Doctoral and Post-doctoral Training in Craniofacial Biology (T90) – Grant #T90 DE021982

  • Principal Investigator: Michael Paine, B.D.S., Ph.D.
  • Sponsor: National Institutes of Health
  • Period: 07/01/2011-06/30/2026
  • Goal: This grant supports education and training for a select cadre of scholars seeking either a formal PhD degree education or post-doctoral training (both DDS and PhD graduates) with a major focus on dental, orofacial and craniofacial health-related disease processes.

Doctoral and Post-doctoral Training in Craniofacial Biology (R90) – Grant #R90 DE022528

  • Principal Investigator: Michael Paine, B.D.S., Ph.D.
  • Sponsor: National Institutes of Health
  • Period: 07/01/2011-06/30/2026
  • Goal: This grant supports education and post-doctoral training for foreign national post-doctoral scholars with a major focus on dental, orofacial and craniofacial health-related disease processes. Selected trainees must have both a dental degree and a PhD, or the equivalent degrees to qualify.

CRE Mouse Models to Study Amelogenesis – Grant #UH3 DE028850

  • Principal Investigator: Michael Paine, B.D.S., Ph.D.
  • Sponsor: National Institutes of Health
  • Period: 08/01/2021-07/31/2024
  • Goal: We have recently development of two knockin mutant mouse lines, these being Ambn-IRESCre and Odam-IRESCre where expression is limited to secretory ameloblasts and maturation ameloblasts respectively. In this UH3 funding period we will examine a series of floxed mutant mice with these novel Cre mouse lines.

Peptide Enabled Tunable Restorative Interface – Grant # R56 DE032903

  • Principal Investigator: Candan Tamerler, PhD
  • Sponsor: NIH
  • Period: 09/01/2022-08/31/2024
  • Goal: To engineer multifunctional peptide-polymer adhesives that work synergistically with SDF to arrest caries and promote tooth remineralization, while inhibiting the stigmatizing side effect of black staining.

Supramolecular nanofibers for recombinant growth factor-free spine fusion – Grant #5 R01 AR072721 (60050309 USC)

  • Principal Investigator: Malcolm L. Snead, D.D.S, Ph.D.
  • Sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases
  • Period: 07/12/2018-04/30/2024
  • Goal: To develop a highly effective strategy to regenerate bone using recombinant growth factor-free bioactive nanoscale materials, suitable to spine fusion and other orthopaedic applications. The nanofiber scaffold developed in this work will be used either on its own or in combination with bone marrow stromal cells (BMSC) rather than with recombinant growth factor. Such an approach could obviate the need for recombinant factors, thereby providing a safer and more effective therapeutic strategy for bone regeneration in spinal fusion and other orthopaedic applications.

Multispecies biofilm for investigate non-antibiotic therapies in dentistry (MISFAITH) – Project Number: 015562-00001

  • Principal Investigator: Malcolm L. Snead, D.D.S, Ph.D.
  • Sponsor: The Research Council of Norway, University of Oslo
  • Period: 09/01/2022-08/31/2027
  • Goal: This project is to provide knowledge and laboratory advances including several nano-biotechnologies to address peri-implant disease. These include identification and refinement of small peptides (6-10 amino acids) that demonstrate high affinity and selectivity for binding to the atomic face of titanium and Ti-alloys used in implants. Titanium binding peptides (TiBP) can be chemically synthesized and can be made to include a second bioactive molecule, producing a bifunctional peptide, that binds only to the implant surface to deliver a bioactive signal to the host.

Protein methylation pathways that control genetic susceptibility to environmental pollutants in the occurrence of craniofacial defects – Grant #5 R01 DE030928

  • Principal Investigator: Jian Xu, Ph.D.
  • Sponsor: National Institutes of Health
  • Period: 07/01/2021-06/30/2026
  • Goal: The major goal of this project is to dissect genetic and environmental mechanisms regulating craniofacial tissue morphogenesis and stress responses.