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Hajishengallis Laboratory

Laboratory of Innate Immunity & Inflammation

The scientific focus of our laboratory is at the host-microbe interface of the oral mucosal barrier. We investigate how these local interactions cross-talk with systemic immunity and aim to define conditions that maintain homeostasis as well as understand the mechanisms by which homeostasis breaks down leading to disease. Our research has illuminated novel mechanisms of homeostatic regulation of immunity, microbial dysbiosis, and inflammation, and has been published in pre-eminent journals, such as, Nature Immunology, Science Translational Medicine, Cell, Cell Host & Microbe, Journal of Clinical Investigation, Nature Communications, PNAS, Science Signaling, New England Journal of Medicine, Nature Reviews Immunology and Nature Reviews Microbiology. We combine basic scientific and translational research, leading to innovative approaches to clinical problems, such as exemplified by periodontal disease, where our preclinical work has led to clinical trials of therapeutic compounds.

The therapeutic compound AMY-101 blocks complement activation and protects against periodontal disease.

Neutrophil and Lymphocyte Homeostasis in Periodontitis
The main goal of this project is to show that periodontitis associated with leukocyte adhesion deficiency is caused by dysregulated overexpression of IL-17 by lymphocytes, driven by the disruption of a homeostatic mechanism that coordinates the recruitment and efferocytosis of neutrophils with their production.

Impact of Aging on the Immune and Regenerative Host Response
This project is designed to investigate the hypothesis that aging-related deficiency of DEL-1 may contribute to dysregulation of progenitor niches and osteogenesis, thereby leading to impaired bone regeneration in old age.

Regulation of functional immune plasticity in the oral mucosa
The focus of this project is to test the hypothesis that tissue-specific proteins act as local endogenous regulators of functional immune plasticity by regulating the initiation and resolution of oral mucosal inflammation.

Complement-targeted host modulation in periodontitis
The primary goal of this project is to determine the mechanisms of complement involvement in periodontitis and develop complement-targeted therapeutic interventions.

Regenerative wound healing via inflammation-modulating biomaterials
This project is designed to test the hypothesis that modulating the HIF-1α environment via an injectable HIF-1α agonist drug/hydrogel construct leads to bone regeneration.

The DEL-1/β3 integrin axis promotes regulatory T cell responses during inflammation resolution Li et al, J Clin Invest, Epub ahead of print DOI: 10.1172/JCI137530

Innate Immune Training of Granulopoiesis Promotes Anti-tumor Activity Kalafati et al, Cell, 183:771-785 (2020).

Hematopoietic progenitor cells as integrative hubs for adaptation to and fine-tuning of inflammation Chavakis T, Mitroulis I, Hajishengallis G, Nat Immunol, 20:802-811 (2019).

DEL-1 promotes macrophage efferocytosis and clearance of inflammation Kourtzelis et al, Nat Immunol, 20:40-49 (2019).

Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity Mitroulis et al, Cell, 172:147–161 (2019).

The oral microbiota: dynamic communities and host interactions Lamont RJ et al, Nat Rev Microbiol, 16:745–759 (2018).

A dysbiotic microbiome triggers TH17 cells to mediate oral mucosal immunopathology in mice and humans Dutzan N et al, Sci Transl Med, 10:eaat0797 (2018).

Novel mechanisms and functions of complement Hajishengallis G et al, Nat Immunol, 18:1288-1298 (2017).

Secreted protein Del-1 regulates myelopoiesis in the hematopoietic stem cell niche Mitroulis et al, J Clin Invest, 127:3624-3639 (2017).

Periodontitis: from microbial immune subversion to systemic inflammation Hajishengallis G, Nature Rev Immunol. 15: 30-44 (2015).

DEL-1 restrains osteoclastogenesis and inhibits inflammatory bone loss in nonhuman primates Shin J et al. Sci Transl Med, 7:307ra155 (2015).

Antagonistic effects of IL-17 and D-resolvins on endothelial Del-1 expression through a GSK-3β-C/EBPβ pathway Maekawa T et al. Nat Commun, 6:8272 (2015).

Porphyromonas gingivalis manipulates complement and TLR signaling to uncouple bacterial clearance from inflammation and promote dysbiosis Maekawa et al, Cell Host Microbe, 15:768–778 (2014).

Defective neutrophil recruitment in leukocyte adhesion deficiency type I disease causes local IL-17-driven inflammatory bone loss Moutsopoulos NM, et al. Sci Transl Med, 229ra40 (2014).

The keystone-pathogen hypothesis Hajishengallis et al, Nat Rev Microbiol, 10:717-725 (2012).

The leukocyte integrin antagonist Del-1 inhibits IL-17-mediated inflammatory bone loss Eskan MA et al. Nat Immunol, 13:465-473 (2012).

Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement Hajishengallis G et al, Cell Host & Microbe, 10:497-506 (2011).

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Tetsuhiro Kajikawa

Tetsuhiro Kajikawa, DDS, PhD (Research Associate) earned his D.D.S. degree at Osaka University School of Dentistry in 2006. He went on to complete his Ph.D. degree at Osaka University Graduate School of Dentistry focusing on PLAP-1, a molecule that is specifically expressed in periodontal ligament. After a term as a clinician at Osaka University Dental Hospital, he joined the Hajishengallis laboratory in 2014 as a postdoctoral fellow focusing on the role of homeostatic molecules and the complement system in periodontal health and disease. He is currently a Research Associate and Lab Manager. His current project involves the role of innate lymphocytes in the context of leukocyte adhesion deficiency.

Xiaofei Li

Xiaofei Li, PhD (Research Associate) completed her B.A. degree in Life Sciences at Henan University in 2010. She then went on to earn her Ph.D. degree at Medical College of Fudan University in Shanghai, where she focused on the research of innate immunity and vaccine immunology and received Shanghai Outstanding Graduates Awards in 2015. In 2015, Dr. Li joined the Hajishengallis laboratory, where she has been investigating inflammatory cytokines (IL-17, IL-22), mechanisms of inflammation resolution, as well as trained innate immunity as a mechanistic basis linking different inflammatory diseases.

Hui Wang

Hui Wang, PhD (Postdoctoral Fellow) earned his Ph.D. degree in pathogenic microbiology from Fudan University in 2014. In 2017, he joined the Hajishengallis laboratory, where he is studying the role of complement in periodontal disease. Moreover, he is investigating the role of DEL-1 in local and systemic bone loss disorders using an array of transgenic and knockout preclinical models.

Jong-Hyung Lim

Jong-Hyung Lim, PhD (Postdoctoral Fellow) completed his Ph.D. in Immunology at Technische Universität Dresden, Germany in 2016. During his PhD studies, he studied mechanisms of action of the anti-inflammatory protein DEL-1 using distinct animal disease models. Following graduation, he joined the Hajishengallis laboratory in 2018 for further studies on the molecular mechanism DEL-1 in oral and mucosal tissue inflammation and homeostasis. He is currently working on the aging-related alterations of DEL-1 expression in progenitor niches and how this in turn impacts on host immunity, inflammation, and tissue regeneration in old age.

Gundappa Saha

Gundappa Saha, M.Tech, PhD (Postdoctoral Fellow) completed his B.Pharm (2012) from West Bengal University of Technology, Kolkata, India; M.Tech (2014) from Anna University, Chennai, India; and Ph.D. (2020) from the Indian Institute of Technology (IIT) Guwahati, India. He studied host-pathogen interactions and immune evasion by Leishmania donovani and was bestowed with a prestigious “Prime Minister’s Fellowship for Doctoral Research” by Department of Science & Technology, Govt. of India in the field of Immunology and Infection Biology. He joined the Hajishengallis laboratory in September 2020 and is currently studying local and systemic mechanisms that promote inflammation in mucosal barrier sites.

Protein purification at the Hajishengallis laboratory

Awarded Patents
Methods of treating or preventing periodontitis and diseases associated with periodontitis
US 9,579,360 B2. Awarded Feb. 28, 2017
Inventors: George Hajishengallis and John D. Lambris

Mucosal immunogens for novel vaccines
US6030624A. Awarded Feb. 29, 2000.
Inventors: Michael William Russell, George Hajishengallis, Susan K. Hollingshead, Hong-Yin Wu, Suzanne Mary Michalek

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Patent Pending
Compositions and methods of regulating bone resorption
US20170136089A1. Pending.
Inventors: George Hajishengallis, Toshiharu Abe, Jieun Shin


George Hajishengallis, DDS, PhD
Thomas W. Evans Centennial Professor

Department of Basic & Translational Sciences

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Dr. George Hajishengallis
Thomas W. Evans Centennial Professor
Department of Basic & Translational Sciences
geoh@upenn.edu | 215-898-2091