IFI16 is a Periodontitis Modulating Protein

IFI16 是一种牙周炎调节蛋白

基本信息

批准号：
10572886
负责人：
Julie Teresa Marchesan
金额：
$ 13.88万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-01 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10572886
关键词：
AIM2 gene Academia Alveolar Bone Loss Anti-Inflammatory Agents Attenuated Automobile Driving Basic Science Bone Marrow Bone Marrow Transplantation Bone Resorption Cells Chronic Clinical Clinical Sciences Dental Development Disease Experimental Models Funding Gingivitis Goals Immune Immune response In Vitro Inflammasome Inflammation Inflammatory Inflammatory Response Innate Immune Response Interferon Type II K-Series Research Career Programs Latino Lead Mentors Mus Natural Immunity Oral Oral health Pathogenesis Patients Periodontal Diseases Periodontitis Protein Inhibition Proteins Research Research Personnel Role Scientist Severities Stimulus Tissue Sample Tissues Tooth Loss Training Translational Research Woman bone career chemokine craniofacial cytokine experimental study human tissue in vitro Assay in vivo knockout animal microorganism multidisciplinary overexpression personalized medicine sensor

项目摘要

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.

抽象的这是一个指导性职业发展奖，旨在促进牙科、口腔和颅面领域的多样性牙周病专家/科学家 Julie Marchesan 的研究人员 (K01) 申请。候选人是进行指导研究，调查干扰素γ诱导蛋白（IFI16）作为通过黑色素瘤 2 (AIM2) 中缺失的炎症小体调节牙周组织破坏炎症细胞因子/趋化因子的表达。该职业发展奖将使 Marchesan 博士能够： a) 获得机械方法方面的培训，以提高转化研究的质量； b) 发展独立的研究生涯，使她能够与临床和基础科学合作研究人员； c) 增加拉丁裔女性在学术界和独立资助的机构中的代表性在口腔健康研究中。多学科专家团队已同意在朱莉的职业生涯中为她提供支持发展奖。共同导师带来了多学科的专业知识，他们是吉姆·贝克博士（共同导师，牙周病学转化研究）和 Jenny Ting 博士（共同导师，先天免疫和宿主反应）。牙周病（PD）是一种多因素疾病，微生物和易感宿主是关键玩家。虽然大多数情况下帕金森病的治疗都是成功的，但众所周知，高达 30% 的帕金森病患者中度慢性牙周炎患者对治疗反应不佳。 IFI16 最近被确定为参与 PD 发病机制的潜在蛋白质。根据刺激和疾病的类型，IFI16 可以作为抗炎蛋白调节炎症。研究发现 Ifi204-/- 中缺乏这种蛋白质小鼠显着增加了牙周骨质流失的严重程度，加强了这种蛋白质的证据调节炎症。因此，我们假设 IFI16 的功能是减弱宿主反应，引发牙周炎。拟议的应用程序将利用机械方法（过度表达、沉默、基因敲除动物、PD实验模型、骨髓移植、蛋白质抑制和人类诱导牙龈炎的组织样本）以研究 IFI16 作为牙周宿主调节剂的作用回复。该项目将 (SA1) 评估 IFI16 作为体外牙周宿主反应的调节剂组织中 IFI16/AIM2 表达的测定和定量；我们建议 (SA2) 探索 IFI16 阻碍使用 Ifi204 和 Aim2 基因敲除动物进行炎性骨质破坏，并且 (SA3) 我们将鉴定细胞主要通过骨髓移植实验通过 IFI16 帮助驱动炎症反应。这项研究的长期目标是增加对炎症驱动调节的理解针对宿主反应的个性化治疗的开发。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Antepartum periodontitis treatment and risk of offspring screening positive for autism spectrum disorder.

产前牙周炎治疗和后代自闭症谱系障碍筛查呈阳性的风险。

DOI：
发表时间：
2023-04
期刊：
影响因子：
0
作者：
Bose, Carl;Valentine, Gregory C;Philips, Kamaira;Boggess, Kim;Moss, Kevin;Barros, Silvana P;Marchesan, Julie;Wu, Di;O'Shea, Thomas M;Peralta;Goldstein, Ricki;Ramamurthy, Rajam;Beck, James D
通讯作者：
Beck, James D

The "oral" history of COVID-19: Primary infection, salivary transmission, and post-acute implications.

COVID-19 的“口述”历史：原发感染、唾液传播和急性后影响。