George Hajishengallis, DDS, PhD

Professional Biography

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, inflammation, and tissue homeostasis. More recently, the laboratory has been also working on projects regarding the impact of aging on the immune system, regulation of myelopoiesis and trained innate immunity. The combination of basic scientific and translational research has led to innovative approaches to clinical problems, such as exemplified by complement-targeted inhibition of periodontal disease. The research program of the laboratory is mainly supported by the NIH/NIDCR and has published over 200 papers (with over 21,000 citations; h-index 74 – Google Scholar), including publications in journals of general scientific interest, such as Cell, Nature Immunology, Science Translational Medicine, Cell Host & Microbe, New England Journal of Medicine, Journal of Clinical Investigation, Nature Communications, PNAS, Science Signaling, 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. He has been listed as a Highly Cited Researcher (Cross-Field category) by Clarivate Analytics in 2018 and 2020.

Recent Projects

• In collaboration with Dr. John D. Lambris at 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 collaborative project has demonstrated that complement inhibition by a C3-targeted drug (compstatin Cp40) 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. In 2019, a clinically developed Cp40 drug (AMY-101; Amyndas Pharmaceuticals) received Investigational New Drug (IND) approval by the U.S. Food and Drug Administration for the conduct of the first clinical study to evaluate its efficacy in adults with periodontal inflammation (gingivitis) (ClinicalTrials.gov Identifier: NCT03694444).
• 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 relevant animal models. This collaboration has moreover associated naturally occurring chronic periodontitis in old mice to aging-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. We are 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 1 (LAD-1). Although LAD-1 periodontitis was 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-1 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-1 and relevant animal models, which are currently under further investigation to understand the underlying cellular and molecular mechanisms.
• 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, which holds that 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. The PSD model bypasses the ‘chicken-or-the-egg’ question on whether dysbiosis initiates inflammation, or vice versa, and rather places an emphasis on the continuous cyclic process in which dysbiosis and inflammation are reciprocally reinforced and constitute the actual driver of periodontitis.

Honors / Credentials

• Highly Cited Researcher: Cross-Field category; Clarivate Analytics (2018, 2020)
• NIH MERIT Award (2016 – Present)
• Advisory Board Member, Aegean Conferences (2016 – Present)
• Thomas W. Evans Centennial Professor, University of Pennsylvania, Penn Dental Medicine (2015 – Present)
• Editor, Current Topics in Innate Immunity II – Springer (2012); Oral Microbiology and Immunology 2nd ed. – ASM Press (2014); Oral Microbiology and Immunology 3rd ed. – ASM Press (2019); Oral Mucosal Immunity and Microbiome – Springer-Nature (2019)
• 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
• Associate Editor, Journal of Immunology (2009 – 2013), Molecular Oral Microbiology (2009-present); Journal of Clinical Periodontology (2017 – Present). Editorial Board Member, Journal of Dental Research (2008-2010 & 2016-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)

News / Media

• Priming the Immune System to Attack Cancer »
• New Insights into Autoimmune Disease »
• Stimulating Immune Cleanup Crew Offers Affordable Possibility for Treating Rare Genetic Disorder »
• To Resolve Inflammation, Location Matters »
• Drivers of Inflammation Provide Valuable Targets for New Gum Disease Therapies »
• By Altering Bone Marrow, ‘Training’ Can Prepare Innate Immune System for Future Challenges »
• Bone Marrow Protein May Be Target for Improving Stem Cell Transplants »
• Translating Science to Practice: Discovery Beyond Dentistry »
• Penn Dental Research Leads to Treatment for Rare Gum Disease »
• George Hajishengallis Receives NIH MERIT Award »
• Complement Inhibitor Reverses Periodontitis »
• Penn Team Reverses Signs of Naturally Occurring Chronic Periodontitis »
• Penn Dental Blocks Bone Loss: Implications for Osteoporosis, RA »
• AAAS Science Update: Gum Disease »
• Penn Dentists Identify Protein that Prevents Bone Loss »
• Penn Dental Medicine Study Blocks Inflammatory Bone Loss in Gum Disease »
• Dr. George Hajishengallis: Sinking His Teeth in to Exciting Research Questions in Periodontal Disease »
• Scientists Find Single Protein That Blocks MS Relapses, Cures Gum Disease »
• Collaborative Penn-Dresden Study Blocks Multiple Sclerosis Relapses in Mice »
• Scientific American: Gingivitis Bacteria Triggers a Tailspin in Your Mouth »
• Gum Disease Bacteria Selectively Disarm Immune System, Penn Study Finds »
• Penn Team Identifies Promising New Target for Gum Disease Treatment »
• Penn Dental Medicine-NIH Team Reverses Bone Loss in Immune Disorder »
• Penn-Led Research Suggests a New Strategy to Prevent or Halt Periodontal Disease »
• New Target for Periodontal Disease »
• New Penn Dental Researcher George Hajishengallis Gets at the Root of Gum Disease »
• The Pros and Cons of Oral Bacteria »
• Growing a World-Class Faculty »
• Mouse study explains bacterium’s unique role in periodontitis: NIH-supported study solves the mystery of a devious oral bacterium »

Selected Publications

Education

• Ph.D., Cellular & Molecular Biology, University of Alabama at Birmingham, 1994
• D.D.S., University of Athens, Greece, 1989

Laboratory Site

View the Hajishengallis Lab »