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.
Lauren C. Yap DMD, MPH
Clinical Assistant Professor, Assistant Program Director for Postdoctoral Pediatric Dentistry Program
Department of Preventive and Restorative Sciences, Division of Pediatric Dentistry
“Oral Microbiome Changes in Children Placed on a Ketogenic Diet”
The ketogenic diet is comprised of a high-fat, low-carbohydrate regimen used for weight management and therapeutic purposes in conditions such as epilepsy, Alzheimer’s disease, and type 2 diabetes. The objective of the study is to determine the effect of the ketogenic diet on the composition and functional potential of the dental plaque microbiome in children. By identifying microbial shifts and changes in metabolic pathways associated with a ketogenic diet, critical insight can be provided into the potential oral health implications of ketogenic dietary therapy. The link between carbohydrate consumption and the pathogenesis of dental caries is well-documented, however the impact of the ketogenic diet on oral ecology remains largely unexplored. This pilot study seeks to characterize changes in dental plaque microbial composition following the initiation of this diet regimen. By investigating these shifts, the project intends to unveil how dietary-induced ketosis modulates oral health, potentially informing novel diagnostic and therapeutic strategies for the pediatric populations.
Wenjing Yu, DDS, PhD, DScD, DMD
Assistant Professor, Associate Director of
Predoctoral Orthodontics Program
Department of Orthodontics
“The role of Gli1+ Chondroprogenitor Cells in Degenerative Temporomandibular joint (TMJ) Diseases”
Temporomandibular joint disease (TMD) is a degenerative musculoskeletal disorder that causes morphological and functional abnormalities. Degenerative Joint Disorders (DJD) of the temporomandibular joint (TMJ) represent a challenging and multifaceted group of conditions that severely impact the joint’s function and patient’s quality of life. Histologically, the DJD of the TMJ is caused by damage or breakdown of the joint cartilage between bones. Despite its prevalence and impact, there are no specific therapeutics that target its root cause. We hypothesize that a group of chondroprogenitor cells (CPC) plays a critical role in maintaining bone homeostasis and preventing the progression of degenerative joint disease in the TMJ. This proposed study aims to identify novel endogenous stem/progenitor cell sources for cartilage tissue regeneration, with a focus on Gli1+ CPCs, derived from the mandibular condyle, that exhibit cartilage regenerative capacity.
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.