About

Emi Shimizu is an Associate Professor in the Department of Oral Biology at Rutgers School of Dental Medicine. Her research focuses on the molecular and physiological mechanisms regulating tertiary dentin formation from dental pulp cells, as well as pulp regeneration technology using induced pluripotent stem cells (iPSC) and oral stem cells. She has identified the role of the IGF1-ephrinB1 axis in tertiary dentin formation and tooth development using genetic mouse models. Her work has been supported by a $2 million grant from the National Institutes of Health and additional funding from Colgate-Palmolive to develop methods for replicating the human oral environment in vitro, aiming to replace animal studies for periodontitis drugs. Dr. Shimizu holds a PhD from the Department of Endodontics at Nihon University Graduate School and a Certificate for Advanced Education Programs from the Department of Endodontics at New York University College of Dentistry.

Research topics

• Medicine
• Biology
• Dentistry
• Cell biology
• Materials science
• Computational biology
• Microbiology
• Biochemistry
• Bioinformatics
• Endocrinology
• Chemistry
• Biomedical engineering
• Immunology
• Intensive care medicine
• Internal medicine
• Cancer research
• Pathology

Selected publications

• Editorial: Expanding knowledge on mineralized tissues in dental science: enamel, dentin, and pulp tissue

  Frontiers in Dental Medicine · 2026-03-11

  articleOpen access1st authorCorresponding

  The mineralized tissues of the mouth-including enamel, dentin, pulp, and alveolar bone-play essential roles in dental health and have long been central to investigations in dental research. Recently, growing attention has been paid to the interactions between these hard tissues and their surrounding tissues, offering new perspectives on disease mechanisms and treatment strategies.Regarding enamel, the classical concept of demineralization and remineralization mediated by oral bacteria, dietary substrates and saliva was established decades ago and continues to be an active focus of research. More recent advances include restorative approaches such as resin infiltration for managing partially demineralized enamel and biomimetic strategies designed to replicate the hierarchical structure of enamel.In the research on the dentin-pulp complex, insights from bone biology have contributed to a better understanding of pulpal characteristics. At the same time, the development of dental materials with improved biocompatibility and sealing ability, particularly hydraulic calcium silicate-based materials, has renewed global interest in vital pulp therapy. This renewed interest stems from growing evidence that these materials can promote favorable biological responses, such as dentin bridge formation, pulpal healing, and reduced inflammatory activity. As a result, this progress has begun to challenge the traditional diagnostic distinction between reversible and irreversible pulpitis, suggesting that these terms may no longer fully reflect current biological and therapeutic concepts.

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• Editorial: Perivascular niche and stem cell signaling in tooth

  Frontiers in Cell and Developmental Biology · 2025-01-31 · 1 citations

  editorialOpen accessCorresponding

  Perivascular niche is the micro space that serves as a stem cell reservoir and is an essential part of maintaining physiological conditions and influencing the pathological conditions of dental tissues (Shi et al., 2003). Senescence is one of the most important elements in regulating stem cell ability (López-Otín et al., 2023). Most recently, Li et al. presented the first spatially resolved transcriptomic landscape of murine jawbone including dental tissues, and uncovered DNA methylation as a crucial mechanism underlying transforming growth factor beta 1 (TGF-β1)-induced periodontal ligament stem cell (PDLSC) senescence (Li et al., 2024). Ju et al. reported that ectonucleotide pyrophosphatase/phosphodiesterase (ENPP) 1 is crucial for TGF-β1-induced PDLSC differentiation (Ju et al.). ENPP modulates the mineralization efficacy driven by adenosine triphosphate released from dental pulp cells in response to intrapulpal pressure (Techatharatip et al., 2018). In observing stem cell behavior, cell differentiation, maturity, and spatiotemporal understanding between stem cells and blood vessels, mouse incisor is a good model for tracing cellular genetic changes. In dental pulp, there are the fundamental cell-to-cell communications that orchestrate tooth formation, angiogenic-odontogenic coupling, a distinct mechanism compared to the angiogenic-osteogenic coupling in bones (Matsubara et al., 2022).Tooth formation is a complex process controlled by genetic information and environmental factors (Murashima-Suginami et al., 2021). Because root dentin formation is an important part of tooth formation, it is valuable to clarify the precise control mechanisms of root dentin formation, and more specifically, the differentiation process of pulp stem cells in the tooth root. Due to the process of dentin formation in the root is different from that in the crown, several unique factors must be involved in the formation of root dentin. Identifying these unique factors may help understand the process of adult root dentin formation and root regeneration. Cui et al. harvested tissues from the labial and lingual sides of mouse incisors and conducted microarray analysis. Gene ontology (GO) analysis of differentially expressed genes indicated the critical role of extracellular matrix in the discrepancy of dentin formation between root and crown, for which hemicentin-1 (Hmcn1) was selected as the target gene. In addition, single-cell RNA sequencing analysis showed the expression pattern of Hmcn1 at different developmental stages in mouse molars (Cui et al.). The spatiotemporal expression of HMCN1 in mouse incisors and molars was detected by immunohistochemical staining as well. This group also investigated the functions of HMCN1 in human dental pulp cells, including proliferation, differentiation, and migration. Uncovering expression patterns of the spatially complicated but precisely differential gene expression will strengthen tissue area-specific target treatment in the future.Both human and rodent molars have multiple roots and are formed through similar developmental sequences. It is considered that the formation of the tooth root and its surrounding structures including PDL and alveolar bone is important for tooth eruption (Ono et al., 2016). Tooth eruption, a crucial part of tooth development and regeneration, involves alveolar bone anabolism and catabolism. Periodontium, which surrounds teeth, is derived from dental follicle stem cells (DFSCs). During tooth eruption, DFSCs inhibit osteoclast differentiation by releasing extracellular vesicles containing Annexin A1 (ANXA1) and its mediated pathway, thereby preventing premature tooth eruption.Elucidation of this mechanism is extremely important for the understanding and treatment of abnormal tooth eruption diseases and the tooth regeneration process (Sun et al.).Teeth and periodontal tissues are able to regenerate due to the inherent autonomous ability of their constituent cells. However, once huge deformation occurs, it is difficult to reproduce the integrated nature of tissue. This situation calls for regenerative therapies using bioengineering tools that maximize the potential of stem cells (Yang et al., 2019).Zheng et al. reported that N-acetylcysteine (NAC) is a stable, safe, and highly bioavailable antioxidant that shows promising prospects in bone tissue engineering due to the ability to attenuate oxidative stress and enhance the osteogenic potential and immune regulatory function of cells. This group systematically introduced the antioxidant mechanism of NAC, analyzed the advancements in NAC-related research involving mesenchymal stem cells (MSCs), precursor cells, innate immune cells, and animal models, discussed its function, and placed particular emphasis on the innovative applications of NAC-modified tissue engineering biomaterials (Zheng et al.).Perivascular cells as MSCs in human dental pulp and periodontal tissue express NOTCH3 and they are very similar and composed of identical subpopulations. In addition to perivascular MSCs, endothelial cells, Schwann cells, and fibroblasts, etc. construct perivascular niches (Pagella et al., 2021). Understanding the mechanisms of homeostasis and maintenance of dental perivascular niches by the intra and extracellular signals is essential to promote the development of dental regenerative medicine. Dental niche cells in tooth formation participate in tooth development, which may shed light on designing next-generation tooth bioengineering strategies to achieve the eventual goal of de novo tooth regeneration (Hu et al., 2022). In this regard, further studies on the formation of dental vascular niches and the involvement of bioengineering technology will further support the acceleration of dental stem cell regenerative medicine.TO, ES, and BL wrote the editorial and invited authors to participate in the collection. All authors contributed to the article and approved the submitted version.

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• Perineural Invasion Exhibits Traits of Neurodegeneration

  Journal of Dental Research · 2025-06-10 · 4 citations

  articleOpen access

  Perineural invasion (PNI) frequently occurs in head and neck squamous cell carcinoma (HNSCC), which correlates with poor survival and induces intractable pain and numbness. There is no effective treatment for PNI or associated pain. To gain a better understanding of PNI at the molecular and cellular level, we produced an orthotopic, syngeneic mouse model of PNI by inoculating mouse oral cancer cells into the infraorbital nerve (ION), a nerve that is susceptible to cancer invasion in patients with HNSCC. Mice with PNI in the ION exhibited both evoked and spontaneous nociception and impaired oral function, mimicking human conditions. PNI resulted in a drastic reduction in the proportion and altered mechanical thresholds in mechanically sensitive trigeminal neurons; axon and myelin abnormalities, as well as phagocytic cells, were observed. The tumor bed is marked by CD4 + and CD8 + T cells, CD68 + cells, and F4/80 + macrophages, while CD4 + , CD8 + , and CD68 + immune cells can be found surrounding the nerve. The intraneural niche is predominantly marked by CD68 that does not overlap with F4/80 but instead overlaps with NF200 and MPZ and occasionally with DAPI, suggesting these are likely phagocytic macrophages or Schwann cells. Finally, our RNA sequencing pathway analysis in mouse and human HNSCC found perturbed pathways in neuroinflammation, mitochondrial dysfunction, and cellular metabolism. Additionally, ION-PNI exhibits nerve degenerative features with perturbed pathways that are observed in Alzheimer, Parkinson, and prion diseases. In conclusion, we report a novel, anatomically relevant in vivo model that could be used to study the cellular and molecular mechanisms of PNI-induced neuropathies. Importantly, we found that PNI resembles neurodegenerative diseases with features of altered sensory transduction and conduction, neuroinflammation, and mitochondrial dysfunction, which may underlie peripheral neuropathies, such as pain.

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• Outcome of Vital Pulp Treatment and Regenerative Endodontics

  2024-02-16

  otherOpen access

  Outcomes are variables evaluated during a study to determine the impact of a clinical intervention or exposure on the health of a particular population. In daily clinical practice, the assessment and reporting of treatment outcomes play a crucial role in clinical decision-making. A diverse range of outcomes have been reported in the vital pulp treatment and regenerative endodontic studies conducted to date. This chapter aimed to provide an overview of those outcomes, including the tools used and the timing of their measurement.

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• Point-of-care diagnostic devices for periodontitis – current trends and urgent need

  Sensors & Diagnostics · 2024-01-01 · 23 citations

  reviewOpen access

  Point of care (POC) diagnostic devices provide a method for rapid accurate identification of disease through analysis of biologically relevant substances. This review focuses on the utility of POC testing for early detection of periodontitis, a critical factor in treating the disease. Accessing the oral cavity for biological sampling is less invasive when compared to other internal test sites, and oral fluids contain biomarkers indicative of periodontitis. The ease of access makes the mouth an excellent target location for the development of POC devices. In this review, accepted standards in industry by which these devices must adhere, provided by the World Health Organization such as REASSURED and CLIA, are discussed. An overview is provided for many periodontal biomarkers currently being investigated as a means of predicting periodontal disease and its progression. POC devices currently being investigated for the identification and monitoring of periodontal disease such as paper-based and lab-on-a-chip based devices are outlined. Limitations of current POC devices on the market are provided and future directions in leveraging biomarkers as an adjunctive method for oral diagnosis along with AI-based analysis systems are discussed. Here, we present the ESSENCE sensor platform, which combines a porous non-planar electrode with enhanced shear flow to achieve unprecedented sensitivity and selectivity. The combination of the ESENCE chip with an automated platform allows us to meet the WHO's ASSURED criteria. This platform promises to be an exciting POC candidate for early detection of periodontitis.

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• Delayed Tooth Development and the Impaired Differentiation of Stem/Progenitor Cells in Incisors from Type 2 Diabetes Mice

  International Journal of Molecular Sciences · 2024-12-19 · 2 citations

  articleOpen accessSenior authorCorresponding

  Patients with diabetes mellitus (DM) have an increased risk of tooth decay caused by alterations in their tooth development and their oral environment, as well as a tendency to present with pulp infection due to compromised immune response. The present study analyzed the characteristic alterations in tooth development under DM conditions using incisors from db/db type 2 diabetic mouse model (T2DM mice). In micro-CT analyses, T2DM mice showed delayed dentin and enamel formation. Through transcriptomic analyses, pre-ameloblast- and pre-odontoblast-specific genes were found to be significantly decreased in the incisors of T2DM mice, whereas major ameloblast- and mature odontoblast-specific genes were not changed. Stem cell markers were decreased in T2DM mice compared to those from the control mice, suggesting that the stemness of dental pulp cells (DPCs) is attenuated in T2DM mice. In vitro analyses demonstrated that DPCs from T2DM mice have lower colony-forming units (CFU), slower propagation, and diminished differentiation characteristics compared to the control. These data suggest that T2DM conditions could impair the differentiation property of multiple progenitor/stem cells in the tooth, resulting in delayed tooth development in T2DM mice.

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• Effects on dentin nanomechanical properties, cell viability and dentin wettability of a novel plant-derived biomodification monomer

  Dental Materials · 2024-07-26 · 5 citations

  article
  PublisherDOI

• Dynamic Alterations in Acetylation and Modulation of Histone Deacetylase Expression Evident in the Dentine–Pulp Complex during Dentinogenesis

  International Journal of Molecular Sciences · 2024-06-14 · 3 citations

  articleOpen access

  Epigenetic modulation, including histone modification, alters gene expression and controls cell fate. Histone deacetylases (HDACs) are identified as important regulators of dental pulp cell (DPC) mineralisation processes. Currently, there is a paucity of information regarding the nature of histone modification and HDAC expression in the dentine-pulp complex during dentinogenesis. The aim of this study was to investigate post-translational histone modulation and HDAC expression during DPC mineralisation and the expression of Class I/II HDACs during tooth development and in adult teeth. HDAC expression (isoforms -1 to -6) was analysed in mineralising primary rat DPCs using qRT-PCR and Western blot with mass spectrometry being used to analyse post-translational histone modifications. Maxillary molar teeth from postnatal and adult rats were analysed using immunohistochemical (IHC) staining for HDACs (1-6). HDAC-1, -2, and -4 protein expression increased until days 7 and 11, but decreased at days 14 and 21, while other HDAC expression increased continuously for 21 days. The Class II mineralisation-associated HDAC-4 was strongly expressed in postnatal sample odontoblasts and DPCs, but weakly in adult teeth, while other Class II HDACs (-5, -6) were relatively strongly expressed in postnatal DPCs and adult odontoblasts. Among Class I HDACs, HDAC-1 showed high expression in postnatal teeth, notably in ameloblasts and odontoblasts. HDAC-2 and -3 had extremely low expression in the rat dentine-pulp complex. Significant increases in acetylation were noted during DPC mineralisation processes, while trimethylation H3K9 and H3K27 marks decreased, and the HDAC-inhibitor suberoylanilide hydroxamic acid (SAHA) enhanced H3K27me3. These results highlight a dynamic alteration in histone acetylation during mineralisation and indicate the relevance of Class II HDAC expression in tooth development and regenerative processes.

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• The Reparative Function of MMP13 in Tertiary Reactionary Dentinogenesis after Tooth Injury

  International Journal of Molecular Sciences · 2024-01-10 · 3 citations

  articleOpen accessSenior authorCorresponding

  MMP13 gene expression increases up to 2000-fold in mineralizing dental pulp cells (DPCs), with research previously demonstrating that global MMP13 deletion resulted in critical alterations in the dentine phenotype, affecting dentine–tubule regularity, the odontoblast palisade, and significantly reducing the dentine volume. Global MMP13-KO and wild-type mice of a range of ages had their molar teeth injured to stimulate reactionary tertiary dentinogenesis. The response was measured qualitatively and quantitatively using histology, immunohistochemistry, micro-CT, and qRT-PCR in order to assess changes in the nature and volume of dentine deposited as well as mechanistic links. MMP13 loss affected the reactionary tertiary dentine quality and volume after cuspal injury and reduced Nestin expression in a non-exposure injury model, as well as mechanistic links between MMP13 and the Wnt-responsive gene Axin2. Acute pulpal injury and pulp exposure to oral fluids in mice teeth showed upregulation of the MMP13 in vivo, with an increase in the gene expression of Mmp8, Mmp9, and Mmp13 evident. These results indicate that MMP13 is involved in tertiary reactionary dentine formation after tooth injury in vivo, potentially acting as a key molecule in the dental pulp during dentine–pulp repair processes.

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• Epigenetic therapeutics in dental pulp treatment: Hopes, challenges and concerns for the development of next-generation biomaterials

  Bioactive Materials · 2023-05-15 · 28 citations

  articleOpen accessSenior author

  This opinion-led review paper highlights the need for novel translational research in vital-pulp-treatment (VPT), but also discusses the challenges in translating evidence to clinics. Traditional dentistry is expensive, invasive and relies on an outmoded mechanical understanding of dental disease, rather than employing a biological perspective that harnesses cell activity and the regenerative-capacity. Recent research has focussed on developing minimally-invasive biologically-based 'fillings' that preserve the dental pulp; research that is shifting the paradigm from expensive high-technology dentistry, with high failure rates, to smart restorations targeted at biological processes. Current VPTs promote repair by recruiting odontoblast-like cells in a material-dependent process. Therefore, exciting opportunities exist for development of next-generation biomaterials targeted at regenerative processes in the dentin-pulp complex. This article analyses recent research using pharmacological-inhibitors to therapeutically-target histone-deacetylase (HDAC) enzymes in dental-pulp-cells (DPCs) that stimulate pro-regenerative effects with limited loss of viability. Consequently, HDAC-inhibitors have the potential to enhance biomaterial-driven tissue responses at low concentration by influencing the cellular processes with minimal side-effects, providing an opportunity to develop a topically-placed, inexpensive bio-inductive pulp-capping material. Despite positive results, clinical translation of these innovations requires enterprise to counteract regulatory obstacles, dental-industry priorities and to develop strong academic/industry partnerships. The aim of this opinion-led review paper is to discuss the potential role of therapeutically-targeting epigenetic modifications as part of a topical VPT strategy in the treatment of the damaged dental pulp, while considering the next steps, material considerations, challenges and future for the clinical development of epigenetic therapeutics or other 'smart' restorations in VPT.

  PublisherDOI

Recent grants

• The novel functions of matrix metalloproteinase 13 supporting dentin-pulp reparative processes

  NIH · $400k · 2024–2026

• Growth factors-induced dentinogenesis

  NIH · $2.1M · 2020–2023

Frequent coauthors

• Nicola C. Partridge

  New York University

  16 shared

• Yoshifumi Kobayashi

  Rutgers, The State University of New Jersey

  15 shared

• Henry F. Duncan

  Dublin Dental University Hospital

  15 shared

• Yorimasa Ogata

  British Society of Periodontology

  14 shared

• Vivek Kumar

  New Jersey Institute of Technology

  11 shared

• Ryoichiro Saito

  Nihon University

  10 shared

• Naoko Kato

  Center for Forensic Mental Health, Chiba University

  8 shared

• Hiroshi Samoto

  8 shared

Awards & honors

• $2 million from the National Institutes of Health