Penn Dental Medicine


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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 Biochemistry
Oral Tolerance for Hemophilia
The current standard of care for the X-linked bleeding disorder hemophilia is intravenous infusion of recombinant factor VIII (FVIII, for hemophilia A). FVIII is expensive, requires frequent repeated IV injections, and are often targeted by antibody responses, thereby complicating/neutralizing therapy, creating immunotoxicities, and further increasing costs. The goals of this project are to: 1) Develop the next generation of edible transplastomic plants expressing FVIII antigen, ovalbumin, or IL-10 fused to different transmucosal carriers, using cutting-edge chloroplast genetic engineering tools. 2) Continue to define the mechanism of oral tolerance induction/immune regulation, in part through use of a model antigen. 3) Suppress inhibitor formation against FVIII in hemophilia A dogs and develop combination oral immune modulatory therapies.
Funding Source: University of Florida, NIH
Principal Investigator: Dr. Henry Daniell, Professor and Interim Chair

Department of Microbiology
Advanced Design of Tumor Targeted, Neutralization Resistant oHSV Vectors
This study will focus on targeting metastatic cancer tumors with a new weapon: herpes. Viruses have been used to treat tumors before by causing the body to attack foreign invaders, but these viruses can fall short when the body creates antibodies to destroy the virus. Dr. Cohen and a colleague from the University of Pittsburgh will work to create a breakthrough herpes virus that specifically targets tumors and is highly-resistant to antibodies. This would help treat patients’ tumors more effectively and safely than existing treatments.
Funding Source: Spirit Award, NIH
Principal Investigator: Dr. Gary Cohen, Professor

Development of a Novel Antiviral to Treat/Prevent Acyclovir Resistance in Human Ocular Herpes Keratitis
The goal of this Phase I STTR is to initiate the development of an antiviral drug that can be used alone or in combination with ACV in order to diminish the chances of generating viral resistant mutants in recurrent treatment of human ocular herpes keratitis. Dr. Ricciardi’s lab has discovered a potent lead that blocks HSV-1 infection and his studies on FHV-1 also provide a foundation to potentially use the feline natural model for a future SBIR Phase II study
Funding Source: Fox Chase Chemical Diversity Center, NIH
Principal Investigator: Dr. Robert Ricciardi, Professor and Chair

A New Model of Regenerative Wound Healing via Inflammation-Modulating Biomaterial
The potential to regain bone and attachment via drug modulation of a regenerative response would represent an ideal advance in periodontal therapy. This study will test the hypothesis that modulating the HIF-1α environment via an injectable HIF-1α agonist drug/hydrogel construct can lead to significant bone regeneration. This will be tested in the context of bacterially-induced, immune-mediated PD in mice, a validated model of human PD.
Funding Source: Lankenau Institute for Medical Research, NIH
Principal Investigator: Dr. George Hajishengallis, Professor

Department of Oral Surgery/Pharmacology
Double-blind, cross-over, incomplete factorial study to assess the local anesthetic efficacy and safety of CTY-5339 Anesthetic Spray (CTY-5339A), Stage 2: Double-blind Active Comparator Phase
The purpose of this study is to see if one spray of CTY5339-A to the gums above the top front teeth produces longer numbness or better numbness than one spray of benzocaine alone.
Funding Source: Cetylite
Principal Investigator: Dr. Elliot Hersh, Professor

Department of Pathology
Bacteria and Lymphocyte Suppression in Periodontitis
The goal of the study is to determine the underlying mechanism by which a bacterial derived toxin, the cytolethal distending toxin (Cdt), acts to inhibit cell growth and induce cell death and thereby perturb host defenses. These studies will lead to a more detailed understanding of the toxin and provide: (1) important insight into the pathogenesis of disease caused by Cdt-producing bacteria and (2) a rationale on which therapeutic intervention may be developed to prevent or limit disease.
Funding Source: NIH
Principal Investigator: Dr. Bruce Shenker, Professor

Department of Periodontics
The role of NF-kB in Mesenchymal Stem Cells during Diabetic Wound Healing
This study will investigate how diabetes affects mesenchymal stem cells that are important for hard and soft tissue healing. It will test if diabetes activates an inflammatory protein, NF-kB, and mediates the negative effects in these stem cells. The studies may provide a novel therapeutic approach to target this protein to improve the function of the stem cells in the treatment of non-healing diabetic wounds.
Funding Source: NIH
Principal Investigator: Dr. Kang Ko, DScD candidate

Division of Community Oral Health
Expanding Pediatric Training in Predoctoral Dental Education
This project builds on existing efforts at Penn Dental Medicine to expand predoctoral education in both pediatric dentistry and community health to address persistent health disparities and difficulties in accessing oral health care in the medically underserved communities in West Philadelphia. The overall goal is to expand the knowledge, skills, and experiences of students in providing dental care with children birth to age 5.
Funding Source: Health Resources and Services Administration, NIH
Principal Investigator: Dr. Joan Gluch, Professor and Div. Chief

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The Robert Schattner Center
University of Pennsylvania
School of Dental Medicine
240 South 40th Street
Philadelphia, PA 19104-6030