Research at Penn Dental Medicine

The following is an overview of areas being addressed by Penn Dental Medicine researchers:

Bone, Teeth, and Extracellular Matrix. Networks of proteins and polysaccharides form a connective tissue matrix for tissues and organs of the body. SDM scientists working in this area aim to understand the biology of connective tissues at cellular, biochemical, and molecular levels. Cartilage and bone, elastin, and tooth enamel are the major subjects of these investigations. This basic research program is providing an understanding of normal growth mechanisms and may elucidate biological defects leading to osteoarthritis, cleft palate formation, and osteoporosis.

Cranio-facial Genetic Anomalies. The investigation of the DNA and polypeptide sequences that code for the proteins of human enamel (enamelins and amelogenins) will continue to explore the genetic determinants of the more common inherited anomalies of dental enamel, and similar investigations of metabolic and genetic factors influencing osteogenesis.

Dental Care Systems. Oral health services research will be expanded as a result of construction of the Robert Schattner Center, which will allow for new admissions, emergency, oral diagnosis, and dental treatment facilities. Areas of clinical research include access of care issues for HIV positive women; impact of reimbursement, especially dental managed care, and patient valuing of oral health on access to services and patient acceptance of treatment plans; and appropriate educational activities and methodologies for use by oral health professionals in the treatment of medically compromised patients.

Dental Implantology. Current dental implantology protocols have focused on longitudinal evaluation of various new designs and chemical formulation of a variety of newly developed intraosseous implants. The faculty listed above are developing protocols for the investigation of the response of jaw bone cells to the variety of products currently in use, and comparison of the cellular and clinical response to dental implants of patients with known metabolic bone disorders, such as osteoporosis.

Heavy Metal Toxicity/Bone Metabolism. Current studies are exploring the effect of low-level metal toxins on immunologic function, metabolic, and genetic factors influencing osteogenesis, gene expression and cartilage mineralization, osteoclast function, and new therapies for Paget's disease and osteoporosis. Community outreach and clinical involvement in the UPMC Metabolic Bone Disease Clinic concerning osteoporosis health education has produced a cohort of patients available for clinical studies.

HIV/AIDS. The SDM HIV/AIDS initiative will continue with investigation of lingual tonsillar tissue biopsy as a source of lymphoid tissue for estimating HIV load, as well as continuation of studies of oral candidiasis in AIDS, salivary inhibitors of HIV, and clinical trials of new topical oral antifungal agents and novel delivery methods.

Infection and the Host Response. The ability of bacteria to colonize and viruses to infect cells represents a dynamic balance between virulence of the infectious agent and host responses. SDM faculty are utilizing a wide range of techniques in cell and molecular biology to characterize the interaction of host-derived defense mechanisms with bacterial and viral virulence factors. Protein chemistry, gene cloning, immunobiology, and electron microscopic techniques are being employed to dissect the molecular mechanisms involved in these processes.

Invasive Pathogens. The human oral cavity is a dynamic environment which supports over 250 species of bacteria. These bacterial species can be divided into two major groups, gram-positive and gram-negative. The gram-positive bacteria, predominantly the streptococci and Actinomyces species, are usually associated with plaque development and subsequent formation of dental caries. Anaerobic and capnophilic gram-negative bacteria are more often associated with gingivitis and various types of periodontal disease. Specific interactions occur among various species of oral bacteria within these communities as well as between the bacteria and hard and soft tissues of the host. By defining these interactions, scientists are elucidating mechanisms of colonization and disease initiation.

Orthodontics/Human Growth. A longitudinal study has investigated the association of growth factors and the timing and success of two different methods of treating a form of malocclusion (distoclusion) that is common in white adolescents for the past ten years. It will continue be followed with a new protocol designed to examine skeletal and jaw growth in African-American children and its influence on the timing and outcomes of orthodontic treatment.

Pain Studies. SDM's Oral Surgery Unit conducts clinical research focusing on the broad areas of postoperative pain control and local anesthesia. For postoperative pain studies, the oral surgery (dental impaction) pain model, which is considered by the FDA to be the most sensitive clinical model in the development of analgesics for acute pain indications, is employed. During a typical year, this program enrolls between 150 and 200 patients. SDM researchers have played major roles in the eventual FDA approval of a number of analgesic and anesthetic agents, including over-the-counter ketoprofen (Orudis KT), bromfenac (Duract), extended-release etodolac (Lodine-XL), and the transoral lidocaine patch (Dentipatch). In addition, phase 2, 3, and 4 (post-marketing) clinical trials have been conducted for a number of pharmaceutical sponsors.

Periodontal Diseases. A number of bacterial species as well as the host immune response are known to be important factors in the pathogenesis of periodontal disease. Investigators continue to explore the role of these two factors in localized juvenile periodontitis (LJP), with current focus on high leukotoxin-producing strains of Actinobacillus actinomycetemcomitans (Aa), LJP patients with high anti-leukotoxin titers, and the immune response of these patients when their cells are transferred to an experimental animal model (SCID mice) that allows separation of the anti-Aa response from the response to other potential periodontal pathogens.

Product Testing. SDM faculty have an ongoing program of product research, including laboratory and clinical safety and efficacy evaluations of over-the-counter dental products, primarily toothbrushes, mouthrinses, flosses, and dentrifrices (toothpaste). Research has been performed to generate comparative or "new and improved" marketing statements and to enable companies to comply with both the American Dental Association's "Seal of Approval" and the U.S. Food and Drug Administration's regulatory requirements.

Saliva, GCF, and the SDM-GCRC Core Oral Fluids Laboratory. Studies are continuing on specific salivary components, e.g., salivary agglutinins, to determine the molecular mechanisms involved in bacterial aggregation in the oral cavity and its role in susceptibility to chronic dental diseases such as caries and periodontitis; and on the mechanisms involved in salivary inhibition of HIV and its significance in preventing oral transmission of HIV and the progression of HIV/AIDS.

Sleep Apnea and Snoring. Patient questionnaires for assessment of risk for sleep apnea have been validated on selected groups of patients who have already been referred to sleep disorders clinics. Validation of these instruments on more general population samples can provide a means for increased detection of individuals at high risk for sleep apnea, as well as for improved medical screening of patients treated for snoring problems with jaw-positioning dental appliances.

Viral Infection. Herpes simplex viruses (HSVs) cause a variety of human disease, including cold sores, eye and genital infections, and encephalitis. HSV glycoproteins are incorporated into the virion envelope and are expressed on infected cell membranes. Three glycoproteins are essential for viral infection and have been implicated in the entry process. A major objective is to define the steps of virus entry. The focus of the studies is to determine the importance of each of these glycoproteins for virus survival or pathogenesis in humans. The goal is to evaluate the role of the glycoproteins in HSV infection and pathogenesis in order to design a paradigm for intervention.

Research Dr. Bruce Shenker Associate Dean 215-898-8994

Student Research Dr. Joseph DiRienzo Assistant Dean 215-898-6551