Faculty Research

The Division of Biostatistics and Experimental Design collaborates with investigators at the Tufts University School of Dental Medicine (TUSDM) on novel research.  We are also active in teaching and service to the school.

Visit the Biostatistics page.

The main focuses of the Division of Oral Biology lab include:

• Gene expression and regulation in bone formation and tooth development.
• Stem cells and transcription factors in bone tissue engineering and regeneration.
• Translational studies including bone metastasis of breast cancer cells, bisphosphonates associated osteonecrosis of the jaws and osseointegration of dental implants.

Bone sialoprotein (BSP) is a major non-collagenous protein in bone and other mineralized tissues. Our lab has demonstrated that that BSP is expressed during de novo bone formation and in the initial stage of mineralization.

Using transgenic mouse model, we were the first to report the expression of rat BSP promoter in a tissue-specific and developmentally regulated fashion. The transcriptional factor Cbfa1 is a “master gene” in osteogenesis. In Cbfa1-deficient mice there was no bone formation. We are currently investigating the regulation of Cbfa1 on BSP gene expression. In addition to a variety of in vitro studies, we have also used a TVA (a chicken retroviral receptor) model to study the regulatory effect of Cbfa1 on BSP expression in vivo during deferent stages of tooth and bone development.

Using BSP as a unique marker and parameter, we have studied the cell differentiation in bone repair and regeneration. Calvarial and femoral bones, as well as periodontal alveolar bone, have been used in this tissue-engineering project in which both gene-therapy and cell-based in vivo methods have been applied. The migration, differentiation, and function of bone marrow stem cells from BSP-transgenic mice have been studied in periodontal regeneration. We have also first subcloned, sequenced, and characterized hamster BSP genes and reported the BSP expression in the cancer model.

It has recently been found that BSP is expressed in breast and prostate cancer cells that have a strong tendency to metastasize into bone tissues. We have started a series of investigations in determining the mechanisms of BSP gene expression in promoting bone metastasis of tumor cells. We have shown that BSP promotes tumor cells to penetrate blood vessels. Using an intracardiac injection of tumor cells in mice, we have found that BSP gene over-expression in human breast cancer cells enhances the tumor metastasis and transfection with antisense of BSP inhibits this effect.

The tools and methods we routinely employ in our lab include Northern, Southern, Western and in situ hybridizations, transgenic animal model, animal surgery and experimental pathology, tumorigenesis, histology, immunohistochemistry, luciferase assays, PCR, DNA and viral construction, cell and tissue cultures.

For more information, contact Dr. Jake Chen at jk.chen@tufts.edu or 617-636-2729

The mission of the Center for Integrated Tissue Engineering (CITE) is to provide experimental in vitro and in vivo three-dimensional (3D) human tissue models that recapitulate the complex tissue architecture and signaling networks present in human tissue in vivo. Through the fabrication and analysis of 3D tissues, CITE generates novel experimental paradigms that (1) enable investigation into the complex interplay between multiple cell and tissue types in biologically meaningful, 3D tissue context, (2) provide a more comprehensive and global picture of how disease-associated pathways interact with their local microenvironment, and (3) serve as human, “pre-clinical” or “surrogate” tissues that set the stage for the translation of discoveries to the clinic through strategies that will allow target identification and validation in human tissues.

With the increasing need for bi-directional interactions between basic and clinical scientists, CITE has developed powerful new research tools that can help meet the broad scientific needs of the translational research community. Conventional basic science approaches to the dissection of complex biological systems have been based primarily on experimentation in two-dimensional (2D), monolayer culture systems. However, the power of these approaches to simulate biological processes in human tissues has been limited. In light of this, it is now widely accepted that cellular and tissue responses need to be studied in experimental systems that incorporate appropriate 3D context and faithfully mimic their in vivo counterparts. Such 3D tissues generated at CITE now (1) allow evaluation of candidate drugs and compounds in human tissues as novel platforms for design and screening of drugs targeted for specific therapeutic applications, (2) provide validated tissue models for product screening that can predict their safety and efficacy in human tissues as alternatives to animal testing, and (3) accelerate the translational pipeline by validating discovery of disease targets made in conventional 2D culture systems in 3D human tissues.

CITE is providing these services in 3D tissue biology to a broad variety of industrial and academic scientists both within the Tufts community and beyond as a portal to the discovery of pathways linked to human disease pathophysiology that now serves as a paradigm for clinical translation.

For more information contact Director Jonathan Garlick at jonathan.garlick@tufts.edu or 617-636-2444.

Research in the Division of Craniofacial & Molecular Genetics focuses on mineralized tissue (e.g., bones, cartilage, teeth) development, homeostasis, disease, and regeneration. Craniofacial, dental, and skeletal diseases affect large percentages of the population and are a serious health concern, including >1/700 live births, and in aged populations. Research models in the Division include 3D tissue-engineering models, in vivo rodent, rabbit and mini pig models, and genetic zebrafish models for human mineralized tissue diseases.

The Craniofacial and Molecular Genetics Program is directed by Pamela Yelick, Ph.D., who currently holds awards from the National Institute of Health (NIH), National Institutes of Dental and Craniofacial Research and Biomedical Imaging and Bioengineering (NIDCR/NIBIB), and other awards.

Learn more about the Yelick Craniofacial & Molecular Genetics Lab.

The division is known for its research on Sjögren’s syndrome, which is either a primary disorder or in association with other rheumatic disorders, Sjogren’s syndrome is an autoimmune disorder that affects between 1 and 4 million people in the United States, with nine times greater incidence in women than in men. It is characterized by a sicca complex of decreased tears and saliva, burning mouth, and the involvement of other organs and systems in the body.

Sjögren’s syndrome is a disease that attacks the body’s moisture-producing glands, causing tooth decay, gum disease, and other problems. Our research activities include the identification of biomarkers for the disease, research on the effect of omega 3 fatty acids on salivation, assessment of cognitive dysfunction associated with Sjögren’s syndrome, and numerous FDA trials on potential therapeutic interventions.

Clinical Trial Participation

The division frequently recruits individuals for participation in its clinical trials. Depending on the trial, participants may receive a stipend, free dental cleanings or exams, gift certificates, or other incentives. To learn about current trials, call 617-636-3931.

Oral Medicine Clinic Appointments

617-636-3932

Dry Eye and Dry Mouth Research Laboratory

Research Synopsis

Sjögren’s syndrome, a systemic inflammatory autoimmune disease which affects approximately 2 to 4 million American, mostly women, is the leading cause of aqueous-deficient dry eye and dry mouth syndromes. In Sjögren’s syndrome, cells of the immune system attack and destroy lacrimal and salivary gland acinar cells (the secretory cells), either directly or through the production of proinflammatory cytokines. To date, the mechanisms leading to acinar cell loss and the associated decline in lacrimal and salivary gland secretions leading to dry eye and dry mouth symptoms are still poorly understood.

Previous research from this laboratory investigated why the remaining acinar cells are not able to support normal exocrine functions during inflammation. The evidence gathered so far points to a pivotal role of proinflammatory cytokines, especially interleukin-1 (IL-1), in the impaired function of the lacrimal gland associated with inflammation. Specifically, it was found that IL-1 has a dual target in the lacrimal gland: the nerve endings (i.e., inhibition of neurotransmitter release) and the epithelial cells (i.e., inhibition of agonist-induced secretion) leading to insufficient secretion and symptoms of dry eye.

Recently, they discovered that murine lacrimal gland is capable of repair following experimentally induced inflammation (i.e., injury). They have evidence that inflammation results in loss of lacrimal gland acinar cells through programmed cell death, namely apoptosis and autophagy. They also found that during the repair phase, stem/progenitor cells in the lacrimal gland are mobilized and induced to proliferate. Furthermore, they have recently been able to isolate and propagate in vitro, stem/progenitor cells from injured lacrimal glands.

Ongoing research in this laboratory aims to:

• Elucidate the causes of insufficient production of tears and saliva with special emphasis on the autoimmune disease Sjögren’s syndrome.
• Identify and characterize salivary biomarkers for the early diagnosis of Sjögren’s syndrome.
• Investigate the regenerative capacity of the lacrimal and salivary glands following experimentally induced injury.
• Study the role of stem/progenitor cells in repair of the lacrimal and salivary glands.
• Use silk-based scaffolds and mesenchymal stem cells to engineer an implantable fluid-secreting device.

Visit the Oral Medicine Clinic page. 

The Naveh lab is an interdisciplinary lab focused on studying the 3D structure and function of the periodontal ligament and extracellular matrix. In the lab we are combining different modalities of imaging, 3D image analysis, mechanical testing and tissue composition analysis. These modalities include microCT, AFM, Light sheet, multiphoton microscopy, proteomics and Raman spectroscopy. Our approach is focused on understanding the micro and mesoscale to achieve macroscale functional manipulations that can be translated to the clinical setting.

Learn more about the Periodontal Ligament Structure and Function Lab. View Dr. Gili Naveh Profile.