IFI16 is a Periodontitis Modulating Protein

IFI16 是一种牙周炎调节蛋白

• 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
• 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

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.

摘要 这是一个指导职业发展奖，以促进牙科，口腔和颅面的多样性 研究劳动力（K 01）申请朱莉Marchesan，牙周病学家/科学家。候选人是 进行指导性研究，调查干扰素γ诱导蛋白（IFI 16）作为一种 通过黑色素瘤2（AIM 2）炎性小体缺失的牙周组织破坏的调节剂， 炎性细胞因子/趋化因子表达。该职业发展奖将使Marchesan博士能够： a）接受机械方法的培训，以提高其翻译研究的质量; 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;以及c）增加拉丁美洲妇女在学术界和独立资助的机构中的代表性 口腔健康研究。一个多学科的专家团队已同意在这一职业生涯中支持朱莉 发展奖。共同导师带来了多学科的专业知识，是吉姆贝克博士（共同导师， Ting博士（共同导师，先天免疫和宿主反应）。 牙周病（PD）是一种多因素的疾病，有微生物和易感宿主为关键 玩家虽然PD的治疗在大多数情况下是成功的，但众所周知，高达30%的PD患者在治疗过程中会出现严重的并发症。 中度慢性牙周炎患者对治疗反应较差。IFI 16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，IFI 16可以 作为抗炎蛋白调节炎症。在Ifi 204-/-中缺乏这种蛋白质的发现 小鼠显著增加牙周骨丢失的严重程度，这加强了这种蛋白质 调节炎症。因此，我们假设IFI 16的功能是减弱宿主的反应， 导致牙周炎所提出的应用将利用机械方法（过表达，沉默， 基因敲除动物、PD实验模型、骨髓移植、蛋白抑制和人 组织样品诱导的牙龈炎）来研究IFI 16作为牙周宿主的调节剂的作用 反应本项目将（SA 1）评估IFI 16作为牙周宿主反应的体外调节剂 分析和定量组织中的IFI 16/AIM 2表达;我们建议（SA 2）探索IFI 16阻碍 使用Ifi 204和Aim 2和（SA 3）的敲除动物的炎性骨破坏，我们将鉴定细胞 使用骨髓转移实验，主要帮助通过IFI 16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发展。

项目成果

In Vivo Antibacterial Efficacy of Nitric Oxide-Releasing Hyperbranched Polymers against Porphyromonas gingivalis.

• DOI: 10.1021/acs.molpharmaceut.9b00671
• 发表时间: 2019-06
• 期刊: Molecular pharmaceutics
• 影响因子: 4.9
• 作者: Lei Yang;L. Jing;Y. Jiao;Lufei Wang;J. Marchesan;S. Offenbacher;M. Schoenfisch

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

• DOI: 10.1002/jper.21-0277
• 发表时间: 2021-10
• 期刊: Journal of periodontology
• 影响因子: 4.3

Three-Dimensional Volumetric Changes After Socket Augmentation with Deproteinized Bovine Bone and Collagen Matrix.

• DOI: 10.11607/jomi.7961
• 发表时间: 2020
• 期刊: The International journal of oral & maxillofacial implants
• 作者: Morelli T;Zhang S;Monaghan E;Moss KL;Lopez B;Marchesan J
• 通讯作者: Marchesan J

Inflammasomes as contributors to periodontal disease.

• DOI: 10.1002/jper.20-0157
• 发表时间: 2020-10
• 期刊: Journal of periodontology
• 影响因子: 4.3
• 作者: Marchesan JT

An experimental murine model to study periodontitis.

• DOI: 10.1038/s41596-018-0035-4
• 发表时间: 2018-10
• 期刊: Nature protocols
• 影响因子: 14.8
• 作者: Marchesan J;Girnary MS;Jing L;Miao MZ;Zhang S;Sun L;Morelli T;Schoenfisch MH;Inohara N;Offenbacher S;Jiao Y
• 通讯作者: Jiao Y