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Research Updates

A quick update on Penn Dental Medicine research with a snapshot of recent publications and research grant awards:

Recent Publications

Following is a selection of recent publications from Penn Dental Medicine standing faculty — those papers recently added to PubMed; those articles in which faculty were first/last authors include highlights of the clinical significance of the studies.

From the Department of Anatomy and Cell Biology:
Transplantation of gingiva-derived mesenchymal stem cells ameliorates collagen-induced arthritis.
Gu Y, Shi S
Arthritis Res Ther. 2016 Nov 11;18(1):262.
Rheumatoid arthritis, an autoimmune disease highly attributed to abnormal T lymphocytes function, causes systemic inflammation with prominent joints pain, swelling and eventually destruction in the long term. Current treatment requires life-long use of pharmaceutical agents to tune down inflammation and immune function which potentially increase the risk of infection among other complications. Similar disease process can be created in animal model and allow researchers to explore new treatment strategy.

University of Pennsylvania researcher and colleague have shown that stem cell transplants may decrease disease activity in an animal model of rheumatoid arthritis. In a paper published in the journal Arthritis research & Therapy, they show that the transplantation of gingiva-derived stem cells ameliorate disease activity in animal model and restore immune tolerance by inducing T lymphocytes apoptosis (programed death) through the interaction of two proteins called Fas receptor, also known as apoptosis antigen 1, and its ligand FasL. T lymphocytes carry Fas protein on their surface, and when their Fas binds with FasL, a signaling cascade initiates the process known as apoptosis featuring DNA degradation and cell membrane blebbing, and eventually cell death.

A Method to Isolate, Purify, and Characterize Human Periodontal Ligament Stem Cells.
Mrozik K, Gronthos S, Shi S, Bartold PM.
Methods Mol Biol. 2017;1537:413-427.

EGF induces epithelial-mesenchymal transition and cancer stem-like cell properties in human oral cancer cells via promoting Warburg effect.
Xu Q, Zhang Q, Ishida Y, Hajjar S, Tang X, Shi H, Dang CV, Le AD.
Oncotarget. 2016 Dec 1. doi: 10.18632/oncotarget.13771. [Epub ahead of print]

Mesenchymal Stem Cells and Their Role in Dental Medicine.
Mao X, Liu Y, Chen C, Shi S.
Dent Clin North Am. 2017 Jan;61(1):161-172. doi: 10.1016/j.cden.2016.08.006.

Neuronal Release of Cytokine IL-3 Triggered by Mechanosensitive Autostimulation of the P2X7 Receptor Is Neuroprotective.
Lim JC, Lu W, Beckel JM, Mitchell CH.
Front Cell Neurosci. 2016 Nov 23;10:270. eCollection 2016.
Mechanical strain due to increased pressure or swelling activates inflammatory responses in many neural systems. As cytokines and chemokine messengers lead to both pro-inflammatory and neuroprotective actions, understanding the signaling patterns triggered by mechanical stress may help improve overall outcomes.

From the Department of Biochemistry:
Compartmentalized Metabolic Engineering for Artemisinin Biosynthesis and Effective Malaria Treatment by Oral Delivery of Plant Cells.
Malhotra K, Subramaniyan M, Rawat K, Kalamuddin M, Qureshi MI, Malhotra P, Mohmmed A, Cornish K, Daniell H, Kumar S.
Mol Plant. 2016 Nov 7;9(11):1464-1477. doi: 10.1016/j.molp.2016.09.013. Epub 2016 Oct 20.

Bestrophinopathy: An RPE-photoreceptor interface disease.
Guziewicz KE, Sinha D, Gómez NM, Zorych K, Dutrow EV, Dhingra A, Mullins RF, Stone EM, Gamm DM, Boesze-Battaglia K, Aguirre GD.
Prog Retin Eye Res. 2017 Jan 19. pii: S1350-9462(16)30086-6. doi: 10.1016/j.preteyeres.2017.01.005. [Epub ahead of print]

Vaccination via Chloroplast Genetics: Affordable Protein Drugs for the Prevention and Treatment of Inherited or Infectious Human Diseases.
Daniell H, Chan HT, Pasoreck EK.
Annu Rev Genet. 2016 Nov 23;50:595-618. Epub 2016 Oct 21.

From the Department of Endodontics:
Outcome of Revascularization Procedure: A Retrospective Case Series.
Bukhari S, Kohli MR, Setzer F, Karabucak B.
J Endod. 2016 Oct 7. pii: S0099-2399(16)30458-7. doi: 10.1016/j.joen.2016.06.021. [Epub ahead of print]

Apicoectomy of maxillary anterior teeth through a piezoelectric bony-window osteotomy: two case reports introducing a new technique to preserve cortical bone.
Hirsch V, Kohli MR, Kim S.
Restor Dent Endod. 2016 Nov;41(4):310-315. Epub 2016 Jul 5.

Modern Endodontic Microsurgery Concepts: A Clinical Update.
Floratos S, Kim S.
Dent Clin North Am. 2017 Jan;61(1):81-91. doi: 10.1016/j.cden.2016.08.007.

From the Department of Microbiology:
A Conserved Tripeptide Sequence at the C-terminus of the Poxvirus DNA Processivity Factor D4 is Essential for Protein Integrity and Function.
Ricciardi RP, Guan H, Nuth M.
J Biol Chem. 2016 Nov 11. pii: jbc.M116.761908. [Epub ahead of print]
Processivity Factors (PFs) are critical for the replication of nearly all forms of life. Almost all viruses that use DNA as their genetic material require a PF to synthesize DNA. PFs work by keeping the DNA Polymerase (Pol) anchored onto the DNA to prevent it from falling off during replication. Since Pols work with their own PFs and cannot be exchanged with another PF (e.g., a completely different virus), they serve as specific antiviral drug targets. In this J Biol Chem study, Dr. Ricciardi and scientists from his laboratory (Drs. Nuth and Guan) have revealed that in order to be functional, the PF of poxvirus (D4) requires 3 of its 218 building blocks (amino acids glycine215, phenylalanine216, isoleucine217) located on at the tail end of PF to loop-back and make contact with a more internal region. This discovery employed several technologies including biophysics, molecular modeling of crystallographic structures, genetics and virology. As a consequence of this finding, a novel drug that binds to this internal region of PF and blocks infection has been discovered (unpublished). Development of this antiviral PF will lead to new drugs that can block infection by smallpox virus in the event of a bioterror attack as well as treat poxvirus diseases for which there is no approved drug, such as molluscum contagiosum that causes highly contagious skin lesions, especially in children.

More than complementing Tolls: complement-Toll-like receptor synergy and crosstalk in innate immunity and inflammation.
Hajishengallis G, Lambris JD.
Immunol Rev. 2016 Nov;274(1):233-244. doi: 10.1111/imr.12467. Review.

Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections.
Gilchuk I, Gilchuk P, Sapparapu G, Lampley R, Singh V, Kose N, Blum DL, Hughes LJ, Satheshkumar PS, Townsend MB, Kondas AV, Reed Z, Weiner Z, Olson VA, Hammarlund E, Raue HP, Slifka MK, Slaughter JC, Graham BS, Edwards KM, Eisenberg RJ, Cohen GH, Joyce S, Crowe JE Jr.
Cell. 2016 Oct 20;167(3):684-694.e9. doi: 10.1016/j.cell.2016.09.049.

Nasal Immunization Confers High Avidity Neutralizing Antibody Response and Immunity to Primary and Recurrent Genital Herpes in Guinea Pigs.
Persson J, Zhang Y, Olafsdottir TA, Thorn K, Cairns TM, Wegmann F, Sattentau QJ, Eisenberg RJ, Cohen GH, Harandi AM.
Front Immunol. 2016 Dec 26;7:640. doi: 10.3389/fimmu.2016.00640. eCollection 2016.

From the Department of Oral Medicine:
Incidental finding of an extensive oropharyngeal mass in magnetic resonance imaging of a patient with temporomandibular disorder: A case report.
Omolehinwa TT, Mupparapu M, Akintoye SO.
Imaging Sci Dent. 2016 Dec;46(4):285-290. doi: 10.5624/isd.2016.46.4.285. Epub 2016 Dec 20.

The bone regenerative capacity of canine mesenchymal stem cells is regulated by site-specific multilineage differentiation.
Bugueño J, Li W, Salat P, Qin L, Akintoye SO.
Oral Surg Oral Med Oral Pathol Oral Radiol. 2017 Feb;123(2):163-172. doi: 10.1016/j.oooo.2016.09.011. Epub 2016 Sep 28.
Mesenchymal stem cells (MSCs) offer a promising therapy in dentistry because of their multipotent properties. Selecting donor MSCs is crucial because Beagle dogs (canines) commonly used in preclinical studies have shown variable outcomes, and it is unclear whether canine MSCs (cMSCs) are skeletal site specific. This study tested whether jaw and long bone cMSCs have disparate in vitro and in vivo multilineage differentiation capabilities.

The Global Footprint of Oral Medicine Specialists: The University of Pennsylvania Experience.
Stoopler ET, De Rossi SS, Greenberg MS, Sollecito TP.
J Dent Educ. 2016 Dec;80(12):1464-1467.
The aim of this study was to analyze the global footprint of oral medicine specialists who graduated from the University of Pennsylvania oral medicine residency program. In 2016, a cross-sectional electronic survey was distributed to 53 graduates of that program, asking about their current geographical location and professional status. Of those 53 graduates, 23 (43%) completed the survey with 22 reporting their current location and 21 reporting their current professional status. The results showed that 17 graduates were located within the U.S., and five were located internationally. Twelve graduates were in full-time academic positions, three were in part-time academic positions/part-time private practice, three were in full-time private practice, two were in postdoctoral training programs, and one was not employed. This study found that oral medicine specialists trained at the University of Pennsylvania were located both domestically and internationally. The majority held faculty positions at academic institutions with fewer involved in private practice. This program may thus be considered a source of future dental academicians.

From the Departments of Oral Medicine and Oral Surgery/Pharmacology:
An adolescent with limited mouth opening.
Stoopler ET, Alomar D, Alfaris S, Granquist E.
J Paediatr Child Health. 2016 Dec;52(12):1117. doi: 10.1111/jpc.1_13204.

From the Department of Oral Surgery/Pharmacology:
A Gingiva-Derived Mesenchymal Stem Cell-Laden Porcine Small Intestinal Submucosa Extracellular Matrix Construct Promotes Myomucosal Regeneration of the Tongue.
Xu Q, Shanti RM, Zhang Q, Cannady SB, O’Malley BW Jr, Le AD.
Tissue Eng Part A. 2017 Jan 4. doi: 10.1089/ten.TEA.2016.0342. [Epub ahead of print]
In the oral cavity, the tongue is the anatomic subsite most commonly involved by invasive squamous cell carcinoma. Current treatment protocols often require significant tissue resection to achieve adequate negative margins and optimal local tumor control. Reconstruction of the tongue while preserving and/or restoring its critical vocal, chewing, and swallowing functions remains one of the major challenges in head and neck oncologic surgery. We investigated the in vitro feasibility of fabricating a novel combinatorial construct using porcine small intestinal submucosa extracellular matrix (SIS-ECM) and human gingiva-derived mesenchymal stem cells (GMSCs) as a GMSC/SIS-ECM tissue graft for the tongue reconstruction.

Applications of Mesenchymal Stem Cells in Oral and Craniofacial Regeneration.
Shakoori P, Zhang Q, Le AD.
Oral Maxillofac Surg Clin North Am. 2017 Feb;29(1):19-25. doi: 10.1016/j.coms.2016.08.009.

EGF induces epithelial-mesenchymal transition and cancer stem-like cell properties in human oral cancer cells via promoting Warburg effect.
Xu Q, Zhang Q, Ishida Y, Hajjar S, Tang X, Shi H, Dang CV, Le AD.
Oncotarget. 2016 Dec 1. doi: 10.18632/oncotarget.13771. [Epub ahead of print]
“Warburg effect”, the enhanced glycolysis or aerobic glycolysis, confers cancer cells the ability to survive and proliferate even under stressed conditions. In this study, we explored the role of epidermal growth factor (EGF) in orchestrating Warburg effect, the epithelial-mesenchymal transition (EMT) process, and the acquisition of cancer stem-like cell properties in human oral squamous cell carcinoma (OSCC) cells. Our results showed that EGF induces EMT process in OSCC cells, which correlates with the acquisition of cancer stem-like properties, including the enrichment of CD44+/CD24- population of cancer cells and an increased expression of CSC-related genes, aldehyde dehydrogenase-1 (ALDH1) and Bmi-1. We also showed that EGF concomitantly enhanced L-lactate production, while blocking glycolysis by 2-deoxy-D-glucose (2-DG) robustly reversed EGF-induced EMT process and CSC-like properties in OSCC cells. Mechanistically, we demonstrated that EGF promoted EMT process and CSC generation through EGFR/PI3K/HIF-1α axis-orchestrated glycolysis. Using an orthotopic tumor model of human OSCC (UM-SCC1) injected in the tongue of BALB/c nude mice, we showed that treatment with 2-DG in vivo significantly inhibited the metastasis of tumor cells to the regional cervical lymph nodes and reduced the expression of ALDH1 and vimentin in both in situ tumors and tumor cell-invaded regional lymph nodes. Taken together, these findings have unveiled a new mechanism that EGF drives OSCC metastasis through induction of EMT process and CSC generation, which is driven by an enhanced glycolytic metabolic program in OSCC cells.

Phase Four, Randomized, Double-Blinded, Controlled Trial of Phentolamine Mesylate in Two- to Five-year-old Dental Patients.
Hersh EV, Lindemeyer R, Berg JH, Casamassimo PS, Chin J, Marberger A, Lin BP, Hutcheson MC, Moore PA, Group PS.
Pediatr Dent. 2017 Jan 15;39(1):39-45.
This pivotal clinical trial on pediatric dental patients demonstrated that phentolamine mesylate (Oraverse) was safe in 3 to 5 year olds and accelerated the recovery from lip numbess and loss of function in 4 and 5 year olds. It lead the FDA to reduce the lower end of the patient age indications from 6 years of age to 3 years of age.

From the Department of Orthodontics:
Candida albicans Carriage in Children with Severe Early Childhood Caries (S-ECC) and Maternal Relatedness.
Xiao J, Moon Y, Li L, Rustchenko E, Wakabayashi H, Zhao X, Feng C, Gill SR, McLaren S, Malmstrom H, Ren Y, Quivey R, Koo H, Kopycka-Kedzierawski DT.
PLoS One. 2016 Oct 14;11(10):e0164242. doi: 10.1371/journal.pone.0164242. eCollection 2016.

Do catalytic nanoparticles offer an improved therapeutic strategy to combat dental biofilms?
Gao L, Koo H.
Nanomedicine (Lond). 2017 Jan 17. doi: 10.2217/nnm-2016-0400. [Epub ahead of print]

From the Department of Pathology:
In vitro characterization of biofilms formed by Kingella kingae.
Kaplan JB, Sampathkumar V, Bendaoud M, Giannakakis AK, Lally ET, Balashova NV.
Mol Oral Microbiol. 2016 Oct 7. doi: 10.1111/omi.12176. [Epub ahead of print]
Kingella kingae is an oral bacterium that causes infections of skeletal system and heart in children under four years old. K. kingae-associated stomatitis has been reported in both children and adults. Ruptured oral vesicles are present in the majority of K. kingae outbreaks and the relationship between these lesions, K. kingae, and mucosal host immune responses might promote invasive infections. Although biofilm has been coupled with pharyngeal colonization, skeletal infections, and infective endocarditis, no studies have investigated biofilm formation in K. kingae. In our current study we examined biofilm formation in 79 K. kingae clinical isolates using a 96-well microtiter plate crystal violet binding assay and we found that almost half of the K. kingae strains form biofilms. All strains that formed biofilms produced corroding colonies on agar. The major extracellular components of biofilms were protein and DNA. Biofilm formation was inhibited by proteinase K and DNase I. DNase I also caused the detachment of pre-formed K. kingae biofilm colonies. A mutant strain carrying a deletion of the pilus gene cluster pilA1pilA2fimB did not produce corroding colonies on agar, autoaggregate in broth, or form biofilms. Biofilm forming strains have higher level of pilA1 expression. We concluded that biofilm formation is common among K. kingae clinical isolates, and that biofilm formation is dependent on the production of proteinaceous pili and extracellular DNA. Biofilm development may have relevance to the colonization, transmission, and pathogenesis of this bacterium. Extracellular DNA production by K. kingae may facilitate horizontal gene transfer within the oral microbial community.

HIV Protease Inhibitors Alter Amyloid Precursor Protein Processing via β-Site Amyloid Precursor Protein Cleaving Enzyme-1 Translational Up-Regulation.
Gannon PJ, Akay-Espinoza C, Yee AC, Briand LA, Erickson MA, Gelman BB, Gao Y, Haughey NJ, Zink MC, Clements JE, Kim NS, Van De Walle G, Jensen BK, Vassar R, Pierce RC, Gill AJ, Kolson DL, Diehl JA, Mankowski JL, Jordan-Sciutto KL.
Am J Pathol. 2017 Jan;187(1):91-109. doi: 10.1016/j.ajpath.2016.09.006.
Mounting evidence implicates antiretroviral (ARV) drugs as potential contributors to the persistence and evolution of clinical and pathological presentation of HIV-associated neurocognitive disorders in the post-ARV era. Based on their ability to induce endoplasmic reticulum (ER) stress in various cell types, we hypothesized that ARV-mediated ER stress in the central nervous system resulted in chronic dysregulation of the unfolded protein response and altered amyloid precursor protein (APP) processing. We used in vitro and in vivo models to show that HIV protease inhibitor (PI) class ARVs induced neuronal damage and ER stress, leading to PKR-like ER kinase-dependent phosphorylation of the eukaryotic translation initiation factor 2α and enhanced translation of β-site APP cleaving enzyme-1 (BACE1). In addition, PIs induced β-amyloid production, indicative of increased BACE1-mediated APP processing, in rodent neuroglial cultures and human APP-expressing Chinese hamster ovary cells. Inhibition of BACE1 activity protected against neuronal damage. Finally, ARVs administered to mice and SIV-infected macaques resulted in neuronal damage and BACE1 up-regulation in the central nervous system. These findings implicate a subset of PIs as potential mediators of neurodegeneration in HIV-associated neurocognitive disorders.

Mas-related G protein coupled receptor-X2: A potential new target for modulating mast cell-mediated allergic and inflammatory diseases.
Ali H.
J Immunobiol. 2016 Dec;1(4). pii: 115. Epub 2016 Dec 28.

Trends in Susceptibility to Aggressive Periodontal Disease.
Shahabuddin N, Boesze-Battaglia K, Lally ET.
Int J Dent Oral Health. 2016;2(4). doi: 10.16966/2378-7090.197. Epub 2016 Apr 25.

From the Department of Periodontics:
The Effect of Osteopontin and an Osteopontin-Derived Synthetic Peptide Coating on Osseointegration of Implants in a Canine Model.
Fiorellini JP, Glindmann S, Salcedo J, Weber HP, Park CJ, Sarmiento HL.
Int J Periodontics Restorative Dent. 2016 Nov/Dec;36(6):e88-e94. doi: 10.11607/prd.2830.
Osteopontin (OPN) and an OPN-derived synthetic peptide, OC-1016, have demonstrated their potential to enhance osseointegration in vitro. The purpose of this study was to evaluate bone-to-implant contact (BIC) and surrounding bone density (BD) of implants coated with either recombinant human OPN (rhOPN) or OC-1016 as compared with noncoated titanium plasma sprayed (TPS) surface in a canine model. Histomorphometric analysis revealed that at 4 weeks, %BIC and %BD of coated implants were significantly higher than those of noncoated TPS implants. At 12 weeks, %BIC of coated implants was also significantly higher than that of noncoated implants; however, there was no statistically significant difference in %BD. The rhOPN and OC-1016 were concluded to be capable of significantly accelerating the early stage of osseointegration and bone healing around implants.

From the Department of Preventative & Restorative Sciences:
Adhesive Bonding to Hybrid Materials: An Overview of Materials and Recommendations.
Spitznagel FA, Vuck A, Gierthmühlen PC, Blatz MB, Horvath SD.
Compend Contin Educ Dent. 2016 Oct;37(9):630-637.

How to Bond Zirconia: The APC Concept.
Blatz MB, Alvarez M, Sawyer K, Brindis M.
Compend Contin Educ Dent. 2016 Oct;37(9):611-617; quiz 618.
The researchers first demonstrate the efficacy of stem cells transplantation by systemic infusion of gingiva-derived mesenchymal stem cells from normal animal in one single dose, which significantly reduce disease severity and showing increased T lymphocytes apoptosis. They further show that this therapeutic effect depends on FasL/Fas pathway by infusing cells from genetically modified animal without functioning FasL, which fail to induce apoptosis to similar level and has limited effect on arthritis activity.This work expanded the application of dental tissue derived mesenchymal stem cells as potential therapeutic strategy for systemic disease such as rheumatoid arthritis.

(Please Note: Due to the variable nature of when publishers index articles to PubMed, there may be some articles that have come out recently that do not yet appear in the PubMed database, and given the variable nature of when publishers index articles to PubMed, some older articles may only have been added to PubMed recently.)

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Recent Grant Awards

Department of Anatomy & Cell Biology
Approaches to Enhance Lysosomal Function in RPE Cells
Chloroquine retinopathy can lead to the loss of vision in patients, with numbers rising as the use of chloroquine increases. While the drug is known to target the lysosomes of RPE cells, it is unclear how this leads to pathology. This proposal will determine whether novel functions of RPE lysosomes like calcium signaling and secretion are impaired by chloroquine and evaluate the ability of treatments to reduce the damage.
Funding Source: NIH
Principal Investigator: Dr. Claire Mitchell, Associate Professor

FAS Controls Exosome-Mediated miRNA Transfer in MSC-Based Therapy
The craniofacial region is involved in a majority of systemic sclerosis patients, who are identified to associate with bone resorption and fractures as a common clinical feature. the findings of this proposal will better reveal the pathophysiology of systemic sclerosis to provide an efficient stem cell therapy for disease management.
Funding Source: NIH
Principal Investigator: Dr. Chi-Der Chen, Postdoctoral Research, Shi Lab

Department of Biochemistry
Control of Pathogenic Microbes through Disruption of Oral Biofilms Using Therapeutic Proteins Produced in Edible Plant Chloroplasts
This initial research exploration will provide proof of concept that Dr. Henry Daniell’s plant-based, biofilm degrading enzymes will augment the performance of known antimicrobial compounds (eg. essential oils) in Dr. Michel Koo’s in vitro biofilm models.
Funding Source: Johnson & Johnson
Principal Investigator: Dr. Henry Daniell, Professor and Interim Chair

Department of Microbiology
High-throughput SPR for Screening and Characterizing Vaccines
For this Direct-to-Phase II SBIR, Wasatch proposes to capitalize upon Dr. Cohen’s strong preliminary results by building a custom Surface Plasmon Resonance (SPR) sensor for vaccine research that injects 96 samples simultaneously and incorporates an array detector with 384 sensing locations—all while maintaining the data quality and operating protocols of current SPR systems.
Funding Source: Wasatch Microfluidics, NIH
Principal Investigator: Dr. Gary Cohen, Professor

Predicting Epitopes in Vaccine and Therapeutic Antibody Research
A thorough knowledge of the immune response generated in the herpes infected human is key to development of a rational vaccine candidate. Detailed characterization of antigen binding is fundamental to understanding and potentially improving mechanisms of action of vaccines. To support such characterization for large panels of herpes-related antibodies and antigen variant proteins, computational design and analysis methods will be integrated with a high-throughput multiplexed experimental platforms. By enabling a rich analysis at much higher throughput than traditional structural studies, this approach promises to better drive discovery and development of herpes vaccines and therapeutic antibodies.
Funding Source: Wasatch Microfluidics, NIH
Principal Investigator: Dr. Gary Cohen, Professor

Local Endogenous Regulators of Functional Immune Plasticity in the Periodontium
Periodontitis is a prevalent disease causing destruction of the tooth-supporting tissues and may adversely affect systemic health. Preliminary studies indicate that a protein expressed by periodontal tissue resident cells, designated Del-1, acts as a gatekeeper of inflammation. This project investigates the hypothesis that Del-1 additionally promotes resolution of inflammation and restores tissue integrity, thereby paving the way to a new class of endogenous therapeutic molecules for treating periodontitis.
Funding Source: NIH
Principal Investigator: Dr. George Hajishengallis, Thomas W. Evans Centennial Professor

Neutrophil Homeostasis and Periodontitis: Novel Concepts and Treatments
Leukocyte adhesion deficiency Type I (LAD-I) leads to destruction of periodontal bone and premature loss of primary and permanent teeth, and has therefore serious adverse psychological and functional consequences in children. The underlying etiology has been historically attributed to impaired neutrophil surveillance of the periodontal infection, although this form of periodontitis has proven unresponsive to antibiotics and/or mechanical removal of the tooth-associated biofilm. This project investigates the hypothesis that LAD-I–associated periodontitis is driven by the disruption of a key neutrophil homeostatic mechanism that leads to overproduction of a potent bone-resorptive cytokine (interleukin 17) and proposes novel treatments that can block this destructive process.
Funding Source: NIH
Principal Investigator: Dr. George Hajishengallis, Thomas W. Evans Centennial Professor

Department of Oral Surgery/Pharmacology
Defining mechanical injury, hypoxia, and disease progression in TMJ Osteoarthritis and Pain
Disorders of the temporomandibular joint (TMJ) are very common, with over 70% of the population reporting signs or symptoms. Most patients experience a self-limited disease course that is managed with physical therapy and/or NSAIDS. Yet, 15% of the TMJ disorder (TMD) cases present as an aggressive disease recalcitrant to therapies, and lead to the development of chronic centralized pain, making TMDs the second most common musculoskeletal condition.
Funding Source: Oral and Maxillofacial Surgery Foundation
Principal Investigator: Granquist, Eric

A Double-Blind, Partial Cross-Over, Incomplete Factorial Study to Assess the Local Anesthetic Efficacy and Safety of CTY-5339 Anesthetic Spray when Applied to the Cheek Mucosal Tissue in Normal Volunteers
This study will assess the safety and efficacy of an anesthetic spray using ECGs and methemoglobinemia (blood co-oximetry).
Funding Source: Cetylite
Principal Investigator: Dr. Elliot Hersh, Professor

Penn Multidisciplinary Consortium: Personalized Dental, Oral and Craniofacial Tissue Regeneration
In the present study, we will delineate the role of stromal cell-derived IL-6 in the regulation of EMT process and acquisition of stem-like cell properties in ameloblastoma epithelial cells and the underlying signaling mechanisms.
Funding Source: Oral and Maxillofacial Surgery Foundation
Principal Investigator: Dr. Qunzhou Zhang, Senior Research Investigator

Department of Orthodontics
A Novel Anti-Caries Approach to Modulate Virulence of Cariogenic Biofilms
Dr. Koo’s lab has developed a potent new anti-caries approach by combining food-derived antibiofilm agents and fluoride with nanotechnology. Nanoparticle carriers (NPC) can maximize drug efficacy via enhanced retention and pH-activated release of therapeutic agents at the tooth/biofilm interface. Furthermore, NPC can encapsulate the bioactive agents to make them water-soluble, critical to practical formulation development. The low-cost and flexibility of NPC chemistry allows further optimization as well as utilization in a variety of applications (from mouthrinses/toothpaste to dental materials.
Funding Source: NIH
Principal Investigator: Dr. Michel Koo, Professor

Biofilm Elimination and Caries Prevention using Multifunctional Nanocatalysts
The proposed approach using nanocatalysts that synergize with hydrogen peroxide may substantially advance current antibiofilm/anticaries modalities. It integrates a multifunctional strategy that is highly effective in degrading the EPS matrix and killing the bacteria embedded within biofilms, while preventing apatitic demineralization under acidic pH. Importantly, the agents are low cost and biocompatible, facilitating further clinical translation and product development to promote oral health.
Funding Source: NIH
Principal Investigator: Dr. Michel Koo, Professor

Department of Pathology
Role of a Novel Human Mast Cell G Protein Coupled Receptor in Allergy and Inflammation
Mast cells play important roles in allergic and inflammatory diseases. Dr. Ali’s lab has discovered a new receptor protein that is expressed on the surface of human mast cells. Understanding the molecular mechanism of its activation may provide new approaches to modulate allergic and inflammatory diseases.
Funding Source: NIH
Principal Investigator: Dr. Hydar Ali, Professor

Role of PERK Haplotypes in HIV-Associated Neurocognitive Disorders
The success of antiretroviral therapy in controlling HIV replication led to significant improvements in life expectancy. Consequently, the percentage of aging HIV-positive patients are increasing; however, age-related changes in the brain are becoming evident, impacting long-term behavioral and cognitive health of these individuals. This study will assess the mechanisms underlying HIV- and antiretroviral drug-mediated perturbations in cellular and molecular processes that are shown to be dysregulated in age-associated neurodegenerative processes, with the aim of identifying genetic risk factors that may contribute to these perturbations within the brains of HIV-positive patients.
Funding Source: NIH
Principal Investigator: Dr. Kelly Jordan Sciutto, Professor and Chair

Role of Heme Oxygenase-1 Microsatellite Polymorphisms in HIV-associated Neurocognitive Disorders: Utilizing Secoisolariciresinol Diglucose as a Targeted Therapeutic Approach in African American Patients
Human monocyte derived macrophages (hMDM) will be isolated from African American donors and non- African American donors and infected with various HIV tropism in the presence and absence of Secoisolariciresinol diglucose (SDG) to assess: infectivity, changes in secretory profiles, neurotoxicity, and HO-1 signaling.
Funding Source: Icahn School of Medicine at Mount Sinai
Principal Investigator: Dr. Kimberly Williams, Postdoctoral Fellow, Jordan-Sciutto Lab

Department of Pediatrics
Skeletal and Dental Quality in Adolescents with Urinary Stone Disease (USD)
The goals of this study are to: (1) compare high-resolution peripheral quantitative computed tomography (HR-pQCT) measures of trabecular and cortical microarchitecture and tibia and radius strength from micro-finite element analyses in 70 adolescents with USD and 70 healthy participants; (2) perform comprehensive assessment of dentition and its supporting tissues in adolescents with USD; and (3) determine modifiable mediators of bone and dental quality in USD by examining their associations with urinary metabolic profiling and dietary intake.
Funding Source: Children’s Hospital of Philadelphia
Principal Investigator: Dr. Evlambia Hajishengallis, Division Chief

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University of Pennsylvania
School of Dental Medicine
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