IFI16 is a Periodontitis Modulating Protein

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ABSTRACT This is a Mentored Career Development Award to Promote Diversity in the Dental, Oral and Craniofacial Research Workforce (K01) application for Julie Marchesan, a periodontist/scientist. The candidate is conducting mentored research investigating the role of interferon gamma inducible protein (IFI16) as a modulator of periodontal tissue destruction via the absent in melanoma 2 (AIM2) inflammasome and inflammatory cytokine/chemokine expression. This career development award will allow Dr. Marchesan to: a) obtain training in mechanistic approaches in order to increase the quality of her translational research; b) to develop an independent research career allowing her to collaborate with clinical and basic science researchers; and c) to increase the representation of Latino women in academia and in independently funded in oral health research. A multidisciplinary team of experts has agreed to support Julie during this career development award. The co-mentors brings multidisciplinary expertise and are Dr. Jim Beck (co-mentor, translational research in periodontology) and Dr. Jenny Ting (co-mentor, innate immunity and host response). Periodontal disease (PD) is a multifactorial disease that has microorganisms and a susceptible host as key players. While treatment of PD is successful in the majority of cases, it is well known that up to 30% of patients with moderate chronic periodontitis respond poorly to treatment. IFI16 was recently identified as a potential protein involved in PD pathogenesis. Depending upon the type of stimuli and disease, IFI16 can modulate inflammation as an anti-inflammatory protein. The finding that absence of this protein in Ifi204-/- mice significantly increases the severity of periodontal bone loss strengthens the evidence that this protein modulates inflammation. Therefore, we hypothesize that IFI16 functions to attenuate the host response that drives periodontitis. The proposed application will utilize mechanistic approaches (overexpression, silencing, knockout animals, experimental models of PD, bone marrow-transplantation, protein inhibition and human tissue samples induced for gingivitis) to study the role of IFI16 as a modulator of the periodontal host response. This project will (SA1) evaluate IFI16 as a modulator of the periodontal host response in vitro assays and quantifying IFI16/AIM2 expression in tissues; we propose to (SA2) explore IFI16 hindering inflammatory bone destruction using knockout animals for Ifi204 and Aim2 and (SA3) we will identify the cells predominantly helping to drive the inflammatory response via IFI16 using bone marrow transfer experiments. The long-term goal of this research is to increase the understanding of the modulation of inflammation driving the development of personalized treatments targeting host responses.