Bruce J. Shenker, Ph.D. Chair and Professor of Pathology Associate Dean for Research Contact Information Robert Schattner Center University of Pennsylvania School of Dental Medicine Rm 312 Levy Building 240 South 40th Street Philadelphia, PA 19104-6030 Phone: 215-898-5959 Fax: 215-573-2050 Email: shenker@pobox.upenn.edu

Education/Professional Honors and Credentials

• Postdoctoral fellow; Department of Pathology, The John Hopkins University School of Medicine, 1977-1980
• Ph.D. in Immunology; Georgetown University, 1977

Research Interests
Dr. Shenker's laboratory is focused on mechanisms of immunoregulation, microbial pathogenesis and immunotoxicity. Over the past several years, significant progress has been made in our understanding of the etiology and pathogenesis of oral infectious diseases. However, the nature and contribution of the immune system to these disorders remain unclear. It is our hypothesis that the immune system plays a primary role to minimize and/or prevent infection. Furthermore, we propose that immunoregulatory abnormalities contribute to the pathogenesis of and susceptibility to oral infectious disorders such as periodontal disease. In this regard, our investigations have demonstrated that several periodontal pathogens produce factors capable of impairing human T- and B-cell function; these include Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum and Treponema denticola. While each of these immunoinhibitoiry proteins are distinct gene products, they share a common mode of action: cell cycle arrest. To date, we have demonstrated that the A.actinomycetemcomitans immunoinhibitory protein is a member of the family of cytolethal distending toxins; this toxin induces G2 arrest in lymphocytes and eventually leads to activation of the apoptotic cascade. Inn contrast, the inhibitory proteins produced by F. nucleatum and T. denticola induce G1 arrest in lymphocytes. Ongoing studies are focused on determining the structure-function relationship for each of these immunotoxins as well as the molecular mode of action.

A second area of investigation concerns the immuno- and neurotoxicity of mercuric compounds. Mercury and its congeners are extremely toxic substances which exist in several physical and chemical forms: inorganic mercury (Hg++), organic mercury and mercury vapor (Hg0). Sources of human exposure to mercury include: seafood, seeds, foodstuffs, water and dental amalgam. Recently, concern has shifted to the potential hazards of chronic exposure to low levels of mercury and, in particular, the possibility of adverse effects on the human immune system. In this regard, our studies have shown that mercury, at low concentrations, kills human lymphoid cells in a manner that is consistent with apoptosis and that the mitochondrion is the target organelle resulting in development of the permeability transition state and oxidative stress. Ongoing studies are aimed at testing the fundamental hypothesis that human exposure to mercury may cause health deficits by impairing host defense mechanisms. These investigation will ultimately provide information that could be used to develop a rational basis for understanding the health implication associated with exposure to mercurial containing compounds.

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