IFI16 is a Periodontitis Modulating Protein

摘要 这是一个指导职业发展奖，旨在促进牙科、口腔和颅面部的多样性 研究人员(K01)申请朱莉·马切森，牙周病医生/科学家。候选人是 进行指导性研究，调查干扰素γ诱导蛋白(IFI16)作为一种 黑色素瘤缺失2(AIM2)炎性小体和牙周组织破坏的调节因子 炎性细胞因子/趋化因子表达。这一职业发展奖将允许Marchesan博士： A)接受机械方法方面的培训，以提高其翻译研究的质量；b) 发展独立的研究事业，使她能够与临床和基础科学合作 研究人员；以及c)增加拉美裔妇女在学术界和独立资助机构中的代表性 在口腔健康研究方面。一个由多学科专家组成的团队同意在朱莉的职业生涯中为她提供支持 发展奖。联合导师带来了多学科的专业知识，吉姆·贝克博士(联合导师， 牙周学翻译研究)和丁珍妮博士(共同导师、先天免疫和宿主反应)。 牙周病是一种以微生物和易感宿主为关键的多因素疾病 球员们。虽然帕金森病的治疗在大多数情况下都是成功的，但众所周知，多达30%的 中度慢性牙周炎患者对治疗的反应很差。IFI16最近被确定为一种 参与帕金森病发病机制的潜在蛋白。根据刺激和疾病的类型，IFI16可以 作为一种抗炎蛋白调节炎症。发现Ifi204中没有这种蛋白质-/- 小鼠显著增加牙周骨丢失的严重程度加强了这种蛋白质的证据 调节炎症。因此，我们假设IFI16的功能是减弱宿主的反应，即 导致牙周炎。提议的应用程序将利用机械性方法(过度表达，沉默， 基因敲除动物、帕金森病实验模型、骨髓移植、蛋白抑制和人类 用于研究IFI16作为牙周宿主调节剂的作用 回应。该项目将在体外评估IFI16作为牙周宿主反应的调节剂 检测和定量IFI16/AIM2在组织中的表达；我们建议(SA2)探索IFI16的阻碍作用 炎症性骨破坏利用基因敲除动物的Ifi204、AIM2和(SA3)我们将鉴定细胞 主要是通过骨髓移植实验通过IFI16帮助推动炎症反应。 这项研究的长期目标是增加对炎症驱动的调制的理解 针对宿主反应的个性化治疗的发展。

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.