Penn Dental Medicine

Departments & Faculty

George Hajishengallis, DDS, PhD

Thomas W. Evans Centennial Professor
Department of Microbiology

Education

  • D.D.S., University of Athens, Greece, 1989
  • Ph.D., University of Alabama at Birmingham, 1994

Honors/Credentials

  • NIH MERIT Award (2016)
  • Advisory Board Member, Aegean Conferences (2016-present)
  • Thomas W. Evans Centennial Professor, University of Pennsylvania, Penn Dental Medicine (2015-present)
  • AADR/IADR William J. Gies Award in the Biological Research Category (2014)
  • Member of the IADR Distinguished Scientist Awards Committee (2013-2017); Chair of the IADR Subcommittee for the Research in Oral Biology Award (2016-2017)
  • IADR Distinguished Scientist Award in Oral Biology (2012)
  • Research highlighted in Nature Reviews, Faculty of 1000-Biology, NIH/NIDCR website, Scientific American, AAAS Science Update, AADR’s Strides in Science, WHYY-FM (NPR, Philadelphia) and the popular press
  • Editor, Current Topics in Innate Immunity II – Springer (2012); Oral Microbiology and Immunology 2nd ed. – ASM Press (2014)
  • Associate Editor, Journal of Immunology (2009-2013) and Molecular Oral Microbiology (2009-present); Editorial Board Member, Journal of Dental Research (2008-2010 & 2016-present); Review Editor, Frontiers in Molecular Innate Immunity (2011-present)
  • Distinguished University Scholar, University of Louisville (2010-2011)
  • University Scholar, University of Louisville (2005-2010)
  • Japanese Society for the Promotion of Science (JSPS) fellow (2008)
  • Reviewer for NIH Scientific Review Groups (since 2005); Standing Member, NIH/NIDCR Special Grants Review Committee (DSR) (2014-present)
  • Faculty Research Excellence Awards, Louisiana State University School of Dentistry (2004 & 2005)

Research Interests

The field of interest of the Hajishengallis laboratory lies at the host-microbe interface at mucosal surfaces and their work has illuminated novel mechanisms of microbial dysbiosis and inflammation. More recently, the laboratory has identified key molecules involved in the homeostasis of the periodontium and other host tissues. The combination of basic scientific and translational research has led to innovative approaches to clinical problems, such as exemplified by periodontal disease. The research program of the laboratory is mainly supported by the NIH/NIDCR and has published over 150 papers (with over 10,000 citations), including publications in journals of general scientific interest, such as Nature Immunology, Science Translational Medicine, Cell Host & Microbe, Nature Communications, PNAS, Science Signaling, New England Journal of Medicine, Nature Reviews Immunology, and Nature Reviews Microbiology. The laboratory’s research has been featured in Nature Reviews, Faculty of 1000-Biology, the NIH/NIDCR website, Scientific American, AAAS Science Update, WHYY-FM (NPR, Philadelphia) and the popular press. Dr. Hajishengallis was awarded the Distinguished Scientist Award in Oral Biology from the International Association of Dental Research (IADR) in 2012 and a MERIT award from the NIH in 2016.

Recent projects include:

In collaboration with Dr. John Lambris at the Penn’s Perelman School of Medicine, the Hajishengallis laboratory has shown that complement is a major player in the pathogenesis of periodontitis, being involved in both the dysbiotic transformation of the periodontal microbiome and the ensuing destructive inflammation typified by loss of tooth-supporting bone. Most importantly, this collaboration has shown that complement inhibition by a C3-targeted drug (compstatin Cp40; exclusive specificity for human and non-human primate C3) can protect against naturally occurring chronic periodontitis in non-human primates. These findings should be highly predictive of drug efficacy in human periodontitis, since non-human primates have similar periodontal anatomy with humans and periodontitis in these animals shares key clinical, microbiological, and immunohistological features with the human disease. A Cp40-based, clinically developed drug (AMY-101; Amyndas Pharmaceuticals) has become available to the group for initiating human clinical trials in the near future.
In collaboration with Dr. Triantafyllos Chavakis at Dresden University, Germany, the Hajishengallis laboratory has identified the secreted glycoprotein Del-1 as a local gatekeeper of inflammatory cell recruitment by restraining β2 integrin-dependent inflammatory cell adhesion to the endothelium in various tissues, including the periodontium and the central nervous system. Accordingly, recombinant Del-1 was shown to protect against experimental periodontitis and multiple sclerosis in appropriate animal models. This collaboration has moreover associated naturally occurring chronic periodontitis in old mice to age-related deficiency in Del-1, marking the first time that an aging-associated deficiency of a single molecule (Del-1) has linked the aging process to increased susceptibility to a chronic inflammatory disease. The research team is currently testing the hypothesis that Del-1 promotes resolution of inflammation and periodontal tissue homeostasis by acting as a local endogenous regulator of functional immune plasticity.
In collaboration with Dr. Niki Moutsopoulos (NIH/NIDCR) and Dr. Steven Holland (NIH/NIAID), the Hajishengallis laboratory proposed a novel etiology for an aggressive and refractory form of periodontitis associated with leukocyte adhesion deficiency Type I (LAD-I). Although historically attributed to lack of neutrophil surveillance of the periodontal infection, this collaboration showed that the true etiology involves dysregulation of the host response. Specifically, both LAD-I patients and relevant animal models exhibit dysregulated overproduction of IL-23 and IL-17, cytokines that drive inflammatory bone loss. Antibody-mediated blocking of the IL-23/IL-17 axis has resolved immunopathology in both human LAD-I and relevant animal models, which are currently investigated to understand the underlying molecular mechanisms of other manifestations of LAD-I.
In collaboration with Dr. Richard Darveau (University of Washington, Seattle) and Dr. Michael Curtis (Queen Mary University of London), the Hajishengallis laboratory has introduced the keystone-pathogen concept, according to which certain low-abundance microbes can orchestrate inflammatory disease by remodeling a normally benign microbiota into a dysbiotic state. This work has also led to a re-evaluation of the roles of P. gingivalis and other red complex bacteria in chronic periodontitis. Accordingly, George Hajishengallis and Richard Lamont (University of Louisville, KY) have proposed the Polymicrobial Synergy and Dysbiosis (PSD) model of periodontal disease pathogenesis, according to which periodontitis is not a bacterial infection in the classical sense (i.e., not caused by a single or a select few “periopathogens”) but rather represents disruption of host homeostasis by a synergistic and dysbiotic polymicrobial community.

News Releases (since joining Penn Dental):

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