The Joseph and Josephine Rabinowitz Award for Excellence in Research was designed to help Penn Dental Medicine faculty undertake pilot projects that will enable them to successfully apply for extramural sources of funding. Designed through the lens of a researcher, this ongoing grant evaluates research proposals for their scholarly merit, creativity and innovation; the significance of the research in advancing scientific knowledge; the prospects for future extramural funding; the availability of alternate funding sources; and in the case of junior faculty, evidence that the applicant will be working as an independent investigator and forwarding of the School’s research objectives. It was under development as early as 1994 with the first award presented in 2002.
This award was endowed through the generosity of the late Dr. Joseph “Jose” Rabinowitz, an active member of the School’s biochemistry faculty for 29 years, and his wife, the late Dr. Josephine “Josy,” a fellow Penn alum. Josy’s PhD was in the field of education. Her strong endorsement of education and research provided a hand in the development of this grant. Jose was known for his research in lipid and steroid biochemistry, and made the seminal discovery that HMG CoA was a key intermediate in cholesterol biosynthesis. His research helped lead to the development of the important class of cholesterol-lowering drugs known as statins.
The Rabinowitz family continues to support the values and priorities of this award.
Kathleen Boesze-Battaglia, PhD
Professor, Department of Basic and Translational Sciences
Over a third of adults over the age of 60 in the U.S. experience significant vision loss, which results in decreased independence and also serves as a biomarker of decreased health span. Age-related retinal degeneration is the leading cause of such vision loss, affecting almost 200 million people worldwide. The Age-related Eye Disease Study (AREDS) and follow-up AREDS2 has shown an association between foods containing high fat dietary products, fried and refined food, and those enriched with red/processed meat, often referred to as a “Western-style” diet, with such retinal degeneration. Lipids contained in the Western diet are transported in the circulation and between cells in lipoprotein particles. In these studies, we will test our hypothesis that in the eye, local beta-lipoprotein (Blp) assembly and secretion protects the retina against diet-induced lipotoxicity and degeneration.
Katherine Theken, PharmD, PhD
Assistant Professor, Department Oral and Maxillofacial Surgery/Pharmacology
Sex Differences in Post-Surgical Pain and Analgesic Response
The Vining lab has developed triacrylate-based biomaterials that promote dental pulp stem cell proliferation and differentiation in vitro. Triacrylate thiol-ene resins also have high strength (>1 GPa nanoindentation modulus) and strong adhesion (>20 MPa) to dentin. Co-investigator Shu Yang’s lab is developing metal organic framework (MOF) nanoparticles for drug delivery. MOFs bearing organic ligands and inorganic nodes have emerged as a promising class of crystalline nanoporous materials to deliver small molecules or inorganic materials due to abundant binding sites, tunable pore size (1-5 nm) and ultrahigh porosity (up to 90%). Here, we propose to develop a composite of triacrylate thiol-ene resin and stannous fluoride (SnF2) MOFs, which will deliver SnF2 upon exposure to an acidic environment, such as plaque biofilms of carious margins of existing restorations.
Marco Tizzano, PhD
Associate Professor, Department Basic and Translational Sciences
The Bitter Taste Signaling Pathway in Gingival Macrophages Participates in Anti-inflammatory and Bone Repairing Responses
Periodontal disease affects nearly 50% of US adults over age 30. We previously discovered taste cell-like solitary chemosensory cells in the gingiva (gSCCs) and preclinically demonstrated their protective antimicrobial function against periodontal bone loss. Recently, we observed the presence of the taste signaling pathway also in gingival macrophages (gMΦs). While gSCCs participate in the gingival epithelial barrier by promoting anti-microbial peptide release, gMΦs participate as 2nd level of protection by evoking anti-inflammatory response that promotes bone repair. With this proposal, we will determine the anti-inflammatory role of gMΦs in response to bitter compounds in reducing periodontal bone loss. In sum, gMΦs and gSCCs are novel targets for the treatment of periodontal disease and show great potential for a preventive approach by a daily routine of oral care that includes the use of taste receptor activators (e.g. in toothpaste or mouthwash).
Myra F. Laird, PhD
Assistant Professor, Department of Basic and
Translational Sciences
Multiscale Analyses of Longitudinal Human Dental Wear
Despite numerous studies on dental wear, our understanding of how teeth change with wear throughout an individual’s lifespan is limited. Longitudinal studies have been constrained to limited-term projects involving living subjects or studies of museum specimens. The central goal of this proposal is to investigate the impact of longitudinal dental wear in humans across 50 years of simulated chewing at four distinct scales: dental function, occlusal topography, dental microstructure, and elemental composition. To achieve this, we will utilize an Artificial Resynthesis Technology (ART VII) chewing simulator to chew foods with different food material properties using unworn occluding pairs of adult third molars. The proposed study will: 1. deliver the first integrated dataset of changes associated with longitudinal dental wear, 2. document changes in elemental composition with dental wear, 3. capture the onset and development of dental senescence, and 4. establish a model for future projects combining dental data.
Chenshuang Li, DDS, PhD, DMD
Assistant Professor, Department of Orthodontics
Global Transcriptional Analyses of A Novel Type of Protein-Based Reprogrammed Cells
Patients suffering from congenital craniofacial disorders, degenerative pathologies, and trauma experience cumbersome difficulties in their daily lives due to bone and skeletal muscle deficits. Unfortunately, regeneration of damaged craniofacial tissue is extremely difficult and often unsatisfactory because the endogenous precursor cells are insufficient in number and/
or regenerative capability. Meanwhile, the inherent tumorigenicity and/or tumor-supporting properties make the currently available pluripotent and multipotent cells undesirable candidates for tissue regeneration. Fibromodulin (FMOD) reprogrammed (FReP) cells are a promising multipotent cell source that can be potentially applied to craniofacial tissue regeneration with a low risk of tumorigenesis. In this study, we will perform an in-depth transcriptomic profile of the transcriptomic profile of FReP cells in comparison with that of induced pluripotent stem cells (iPSCs) to confirm the non-tumorigenic nature of FReP cells is independent of the sex and age of their parental fibroblasts; and track the transcriptomic alteration of bioenergetic-related genes during FMOD reprogramming to gain insight into advancing this technology.
Kyle Vining, DDS, PhD
Assistant Professor, Department of Preventive and Restorative Sciences and Department of Materials Science
Anti-Cavity Metal Organic Framework Resin Composite
The Vining lab has developed triacrylate-based biomaterials that promote dental pulp stem cell proliferation and differentiation in vitro. Triacrylate thiol-ene resins also have high strength (>1 GPa nanoindentation modulus) and strong adhesion (>20 MPa) to dentin. Co-investigator Shu Yang’s lab
is developing metal organic framework (MOF) nanoparticles for drug delivery. MOFs bearing organic ligands and inorganic nodes have emerged as a promising class of crystalline nanoporous materials to deliver small molecules or inorganic materials due to abundant binding sites, tunable pore size (1-5 nm) and ultrahigh porosity (up to 90%). Here, we propose to develop a composite of triacrylate thiol-ene resin and stannous fluoride (SnF2) MOFs, which will deliver SnF2 upon exposure to an acidic environment, such as plaque biofilms of carious margins of existing restorations.
Chider Chen, PhD
Assistant Professor, Department of Oral and Maxillofacial Surgery/Pharmacology
“A Unique Chondrocyte Progenitor Population Maintains Mandibular Bone Homeostasis”
The temporomandibular joint disorder (TMD) is caused by damage or breakdown of the joint cartilage between bones. Unlike
other skeletal tissues, cartilage has remarkably low regenerative potential. Despite its prevalence and impact, there are no specific therapeutics that target the root cause of TMD. Therefore, a new therapeutic approach through identifying and activating endogenous mandibular stem/progenitor cells is urgently needed to manage the disorder. In this study, we propose to characterize a unique Gli1+ chondroprogenitor population between mandibular and femoral condyle by using single cell RNA sequencing analysis. In addition, a CODEX Microfluidics System will be utilized to identify the spatial and molecular characteristics of the Gli1+ chondroprogenitor population. By using these cutting-edge experimental tools, this project supported by the Rabinowitz award will reveal a unique endogenous chondrocyte progenitor population in mandibular condyle that maintains mandibular bone homeostasis and provides a new therapeutic avenue for regenerative medicine in the temporomandibular joint.
Qunzhou Zhang, PhD
Research Assistant Professor, Department of Oral & Maxillofacial Surgery
“Optimization of Gingival Mesenchymal Stem Cell (GMSC)- derived Extracellular Vesicles for Peripheral Nerve Regeneration”
Debilitating peripheral nerve injuries can cause considerable long- term disability. Mesenchymal stem cells (MSCs) have shown great promise for peripheral nerve regeneration (PNR). However, there have been no approved MSC-based products for PNR due to the well-recognized heterogeneity of MSCs.
We pioneered in the isolation of a putative subpopulation of MSC from human gingival tissues (GMSCs). Through non-genetical approaches, we were able to reprogram GMSCs into neural crest- stem like cells (NCSC) or Schwann cell precursor-like cells, which exhibit enhanced pro-nerve regenerative potentials compared with their parental GMSC counterparts. In this proposal, we hypothesize that GMSCs primed under defined NCSC-induction conditions (iGMSCs) are licensed to increase the secretion of extracellular vesicles (EVs) with enhanced pro-nerve regenerative potentials. We will 1) determine the quality and biological functions of EVs secreted by iGMSCs and their parental GMSC counterparts; 2) investigate the pro-nerve regenerative potentials of iGMSC- and GMSC-derived EVs in a sciatic nerve crush injury model in rats.
Accomplishment of this project will support our future NIH or DOD translational grant applications aiming at developing safe and effective cell-free products for PNR.
Flavia Teles, DDS, MS, DMSc
Associate Professor, Department of Clinical and Translational Sciences
“Integrating Omics-Data via Deep Learning to Predict Periodontitis Progression”
Periodontitis is the most common cause of tooth loss among US adults. Further, it increases the risk for systemic conditions such as diabetes, cardiovascular and respiratory diseases. Thus, early identification of periodontitis and of high-risk individuals is critical. However, there are no practical means of doing so.
In this project we will use metagenomic sequencing to determine the subgingival microbiome of patients with severe periodontitis presenting advanced disease progression. Then, we will employ artificial intelligence approaches to devise biological disease classifications and predictive models of clinical outcomes by integrating existing longitudinal immunological, clinical and demographic data with the microbiological information.
Results from this project will support future NIH grant applications aiming at understanding identifying and predicting high risk for periodontitis, and development of more precise and efficient approaches to diagnosis, treatment and prevention.
Yuan Liu, DDS, MS
Research Associate, Division of Restorative Dentistry, Department of Preventive & Restorative Sciences
“Association Between Early Candida Infection (Oral Thrush) and Severe Early Childhood Caries”
Severe early childhood caries (S-ECC) is a major public health problem characterized by dysbiotic oral microbial burden leading to a persistent and virulent biofilm on the teeth of toddlers that causes rampant tooth decay as well as hurts the general health. Emerging clinical evidence has spotlighted the potential role of Candida albicans in S-ECC. Furthermore, our retrospective study revealed that oral thrush (oropharyngeal candidiasis or OPC) detection in toddlers less than 12 months of age was strongly associated with the development of dental caries. However, only cross-sectional human studies have been performed thus far. Longitudinal studies are warranted to better assess the causal association between OPC and S-ECC in toddlers to determine the fungal role in caries. To address this, the proposed research will be focused on conducting a 2-year prospective longitudinal study to (1) investigate the association between early OPC and the onset and severity of S-ECC in a cohort of infants, and (2) evaluate the influence of OPC on the functional plaque microbiome of infants. The Rabinowitz award will allow us to perform a pilot study and collect data for future large-scale mechanistic clinical studies as well as develop novel strategies to prevent S-ECC from a fungal perspective.
