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 Hajishengallis laboratory uses diverse and complementary in vitro and in vivo preclinical models and multidisciplinary research approaches to understand the mechanisms that regulate immunity and inflammation in the oral mucosa and how this in turn impacts systemic health and disease. In this manner, the laboratory and its collaborators have made significant novel contributions that challenged earlier paradigms and provided implications and applications above and beyond the oral immunology field. These include, but are not limited to, the introduction of the keystone pathogen concept; the polymicrobial synergy and dysbiosis model in inflammatory disease; the inflammophilic nature of the dysbiotic oral microbiota; the location-dependent homeostatic principle; the DEL-1–IL-17 balance principle; and the establishment of maladaptive trained myelopoiesis as a mechanistic basis of inflammatory comorbidities. Many of our basic discoveries in model organisms have found application in the treatment of human disease. For instance, our discovery that the central complement component C3 is required for inflammatory periodontal bone loss in different animal models has led to a successful C3-targeted phase 2a clinical trial in patients with periodontal inflammation, with plans for further phase 3 trials. Also of translational importance was our discovery that the aggressive form of periodontitis associated with leukocyte adhesion deficiency type 1 (LAD-1) is not driven by a tissue invasive infection, as traditionally thought, but is rather driven by dysregulation of the IL-23–IL-17 axis. This discovery, made in an animal model of LAD-1, has guided the development of the first successful treatment for this condition in human patients on the basis of antibody-mediated neutralization of IL-23. Our current research efforts focus on understanding the principles that govern tissue-specific homeostatic immunity, bone regeneration upon inflammation resolution, the impact of aging on progenitor cells and immunity, as well as delving deeper into the mechanisms and consequences of epigenetic inflammatory memory in the context of trained myelopoiesis.
Hui Wang, Ph.D. (Research Associate) earned his Ph.D. degree in pathogenic microbiology from Fudan University in 2014. In 2017, as a postdoctoral fellow he joined the Hajishengallis laboratory, where he had studied the role of complement in periodontal disease and investigated the role of DEL-1 in local and systemic bone loss disorders using an array of transgenic and knockout preclinical models. He is currently a Research Associate and Lab Manager. His current project involves the role of clonal hematopoiesis of indeterminate potential in periodontitis and other bone loss diseases.
Jong-Hyung Lim, Ph.D. (Research Associate) 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 role of DEL-1 in oral and mucosal tissue inflammation and homeostasis. He is currently a Research Associate working on aging-related alterations in progenitor niches and how these in turn impact on host immunity, inflammation, and tissue regeneration in old age.
Xudong Wang, Ph.D. (Postdoctoral Fellow) completed his Ph.D. degree in Biology from Tsinghua University, China, in 2018. He completed postdoc training in ophthalmology and cancer biology at Harvard Medical School from 2019-2022. In 2023, he joined the Hajishengallis laboratory, where he is studying macrophage immunometabolic regulation in periodontitis and the impact of aging on trained immunity.
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 investigating local and systemic mechanisms that promote inflammation in mucosal barrier sites as well as cellular and molecular mechanisms that underlie the connection between periodontitis and systemic comorbidities.
Lina Baeesa, B.D.S. (Graduate Student) earned her Bachelor of Dental Surgery from King Abdulaziz University, Saudi Arabia, in 2018. In 2021, she started her clinical training in Orthodontics, completed her residency training for two years, and joined the Hajishengallis laboratory for her Doctor of Science in Dentistry (D.Sc.D.) degree in 2023. Her postdoctoral research interest is focused on molecular mechanisms of inflammation resolution and bone regeneration in old age.
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
Patent Pending
Compositions and methods of regulating bone resorption
US20170136089A1. Pending.
Inventors: George Hajishengallis, Toshiharu Abe, Jieun Shin