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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 the abstract of the publication.

From the Dept. of Anatomy and Cell Biology:
The combination of nano-calcium sulfate/platelet rich plasma gel scaffold with BMP2 gene-modified mesenchymal stem cells promotes bone regeneration in rat critical-sized calvarial defects
Liu Z, Yuan X, Fernandes G, Dziak R, Ionita CN, Li C, Wang C, Yang S. Stem Cell Res Ther. 2017 May 25;8(1):122. doi: 10.1186/s13287-017-0574-6.
Nano-calcium sulfate/platelet rich plasma sandwich-like scaffold is a new and effective bone regeneration scaffold for delivery of stem cells and healing of bone defects. Combination of this scaffold with mesenchymal stem cells and BMP2 has great potential to reconstruct new bone and avoid donor site morbidity for large bone defects.

From the Dept. of Biochemistry:
High efficient multi-sites genome editing in allotetraploid cotton (Gossypium hirsutum) using CRISPR/Cas9 system.
Wang P, Zhang J, Sun L, Ma Y, Xu J, Liang S, Deng J, Tan J, Zhang Q, Tu L, Daniell H, Jin S, Zhang X.
Plant Biotechnol J. 2017 May 12. doi: 10.1111/pbi.12755. [Epub ahead of print]

From the Dept. of Endodontics:
A Comparison of 2- and 3-dimensional Healing Assessment after Endodontic Surgery Using Cone-beam Computed Tomographic Volumes or Periapical Radiographs.
Schloss T, Sonntag D, Kohli MR, Setzer FC.
Endod. 2017 May 17. pii: S0099-2399(17)30247-9. doi: 10.1016/j.joen.2017.02.007. [Epub ahead of print]
The study introduced a precise method of volumetric analysis for the assessment of healing after endodontic microsurgery. This allowed for the comparative evaluation of periapical radiography with three-dimensional CBCT imaging for the exact appraisal and clarification of healing patterns traditionally labeled as incomplete or uncertain, which is significant for endodontic outcome assessment and the treatment planning of failed endodontic cases.

From the Dept. of Microbiology:
Reactivation and Lytic Replication of Kaposi’s Sarcoma-Associated Herpesvirus: An Update.
Aneja KK, Yuan Y.
Front Microbiol. 2017 Apr 20;8:613. doi: 10.3389/fmicb.2017.00613. eCollection 2017.
A traditional concept was that the lytic cycle of a tumor virus presumably does not contribute to oncogenesis simply because the lytic cycle in general leads to lysis and death of host cells. However, accumulative evidence suggests that the KSHV lytic cycle is crucial for tumorigenesis. The article compiled the recent progresses in the research on KSHV lytic replication and informed new strategies for treatment of KSHV-associated human malignancies.

A self-sustained loop of inflammation-driven inhibition of beige adipogenesis in obesity.
Chung KJ, Chatzigeorgiou A, Economopoulou M, Garcia-Martin R, Alexaki VI, Mitroulis I, Nati M, Gebler J, Ziemssen T, Goelz SE, Phieler J, Lim JH, Karalis KP, Papayannopoulou T, Blüher M, Hajishengallis G, Chavakis T.
Nat Immunol. 2017 Jun;18(6):654-664. doi: 10.1038/ni.3728. Epub 2017 Apr 17.

Endogenous developmental endothelial locus-1 limits ischaemia-related angiogenesis by blocking inflammation.
Klotzsche-von Ameln A, Cremer S, Hoffmann J, Schuster P, Khedr S, Korovina I, Troullinaki M, Neuwirth A, Sprott D, Chatzigeorgiou A, Economopoulou M, Orlandi A, Hain A, Zeiher AM, Deussen A, Hajishengallis G, Dimmeler S, Chavakis T, Chavakis E.
Thromb Haemost. 2017 Jun 2;117 (6):1150-1163. doi:10.1160/T16-05-0354. Epub 2017 Apr 27.

From the Dept. of Oral Medicine:
Oral lesions associated with Fanconi anemia.
Stoopler ET, Homeida L, Sollecito TP.
Rev Bras Hematol Hemoter. 2017 Apr – Jun;39(2):175-176. doi: 10.1016/j.bjhh.2017.03.003. Epub 2017 Apr 15.
Fanconi anemia is a rare autosomal recessive disorder characterized by a broad spectrum of physical abnormalities, bone marrow failure and a predisposition to both hematological and solid malignancies. This manuscript highlights the oral findings associated with this condition, including oral squamous cell carcinoma.

From the Depts. of Oral Medicine & Pathology:
Asymptomatic Pigmented Lesions of the Gingiva.
Stoopler ET, Ojeda D, Alawi F.
JAMA Dermatol. 2017 Jun 7. doi: 10.1001/jamadermatol.2017.1614. [Epub ahead of print]
Pigmented lesions of the oral mucosa are encountered on a routine basis in clinical practice. This manuscript highlights a case of gingival pigmentation in a 58-year-old woman of unusual etiology.

From the Depts. of Oral Surgery/Pharmacology & Pathology:
Ameloblastic Fibro-Odontoma of the Maxilla in a Pierre-Robin Sequence Patient.
Kufta K, Kang S, Alawi F, Moran A, Panchal N.
Fetal Pediatr Pathol. 2017 May 30:1-7. doi: 10.1080/15513815.2017.1324547. [Epub ahead of print]
The recent publication “Amelobastic Fibro-Odontoma of the Maxilla in a Pierre-Robin Sequence Patient” is a significant publication because it identifies potential pathology in a particular patient population. In addition, this publication was a collaboration between departments at the School of Dental Medicine (Pathology and OMFS), a collaboration between different schools within the University of Pennsylvania (School of Dental Medicine and School of Medicine), and was authored by a dental student, a resident and faculty from the School of Dental Medicine.

From the Dept. of Orthodontics:
Changes in the buccolingual inclination of first molars with growth in untreated subjects: A longitudinal study.
Sayania B, Merchant M, Josephs P, Chung CH.
Angle Orthod. 2017 May 8. doi: 10.2319/120716-878.1. [Epub ahead of print]
This paper provides norms on the buccolingual inclination of posterior teeth. This information can guide the orthodontists in treating their patients on the final position of maxillary and mandibular molars.

American Board of Orthodontics responds.
Dugoni SA, Chung CH, Tadlock LP, Barone N, Pangrazio-Kulbersh V, Sabott DG, Foley PF, Trulove TS, DeLeon E Jr.
Am J Orthod Dentofacial Orthop. 2017 Jun;151(6):1015-1016. doi: 10.1016/j.ajodo.2017.03.006.

From the Dept. of Orthodontics & Divs. of Pediatric Dentistry & Community Oral Health:
Biofilm three-dimensional architecture influences in situ pH distribution pattern on the human enamel surface.
Xiao J, Hara AT, Kim D, Zero DT, Koo H, Hwang G.
Int J Oral Sci. 2017 Apr 28. doi: 10.1038/ijos.2017.8. [Epub ahead of print]
The development of highly structured bacterial microcolonies that are enmeshed in an EPS-rich matrix creates localized acidic regions on the enamel surface, which serve as demineralizing sites for the onset of early carious lesions clinically known as “white spots”. Here we applied our developed in situ pH mapping method to assess the pattern and localization of acidic pH values throughout the biofilm architecture and across the enamel surface at the biofilm-apatite interface.

From the Dept. of Pathology:
Serum amyloid A: an ozone-induced circulating factor with potentially important functions in the lung-brain axis.
Erickson MA, Jude J, Zhao H, Rhea EM, Salameh TS, Jester W, Pu S, Harrowitz J, Nguyen N, Banks WA, Panettieri RA Jr5, Jordan-Sciutto KL.
FASEB J. 2017 May 22. pii: fj.201600857RRR. doi: 10.1096/fj.201600857RRR. [Epub ahead of print]

From the Dept. of Periodontics:
Morphometric Changes Induced by Cold Argon Plasma Treatment on Osteoblasts Grown on Different Dental Implant Surfaces.
Canullo L, Genova T, Mandracci P, Mussano F, Abundo R, Fiorellini JP.
Int J Periodontics Restorative Dent. 2017 Jul/Aug;37(4):541-548. doi: 10.11607/prd.2916.

A Building with a Provenance: The Thomas W. Evans Building at Penn Dental Medicine.
Kinane DF.
J Hist Dent. 2017 Spring;65(1):7-15.
The Thomas Evans building was spectacular when it opened in 1915 and has now undergone a renaissance that has transformed the school into a functional and facilities rich masterpiece. The mantle was laid down that the building be second to none, it has achieved this with an incredible blend of history, art, modern technology, and open beautiful spaces that need to be seen to be believed.

From the Dept. of Preventive & Restorative Sciences:
Evaluation of a Vibrotactile Simulator for Dental Caries Detection.
Kuchenbecker KJ, Parajon RC, Maggio MP.
Simul Healthc. 2017 Jun;12(3):148-156. doi: 10.1097/SIH.0000000000000201.
Caries detection and diagnosis relies upon fine tactile cues learned over time. Leaving caries behind in a preparation is the #1 reason for dental students’ failure in the clinical board examinations amongst all schools. Utilizing new technologies available to duplicate the sensation of touch may improve and augment the skill acquisition required to accurately remove all caries during the restorative preparation procedure, and shorten the learning curve. This paper was a study that showed expert opinions validated use of a technology replicating the feelings of dental instruments within the tooth during caries removal procedures could be useful in dental education for caries detection, diagnosis and removal procedures.

Surface characteristics of bioactive Ti fabricated by chemical treatment for cartilaginous-integration.
Miyajima H, Ozer F, Imazato S, Mante FK.
Mater Sci Eng C Mater Biol Appl. 2017 Sep 1;78:495-502. doi: 10.1016/j.msec.2017.03.250. Epub 2017 Mar 29.
The aim of the study was to determine titanium treatments that will produce surfaces conducive to integration of cartilage. Apatite formation and chemical pretreatment of Titanium were shown to provide bioactive surfaces that promote chondrocyte differentiation and have a potential to integrate cartilage to titanium to reduce failure of joint implants.

(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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Philadelphia, PA 19104-6030