Barrier Damage and The Immune CascadeNorthwestern University CounterACT Center of Excellence (NUCCX)

屏障损伤和免疫级联西北大学 CounterACT 卓越中心 (NUCCX)

• 批准号: 10682598
• 负责人: ROBERT M LAVKER
• 金额: $ 268.38万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-17 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10682598
• 关键词: Acute; Address; Anti-Inflammatory Agents; Arts; Biological Markers; Burn injury; COVID-19; Chemical Agents; Chicago; Cholecalciferol; Clinical; Clinical Trials; Communication; Communities; Complex; Cornea; Cutaneous; Data Analyses; Development; Disease; Education; Educational workshop; Eye; Eye Injuries; Eyedrops; Fostering; Goals; Health; High Density Lipoproteins; Human; Hybrids; Immune; Immunology; Inflammation; Inflammatory; Injury; Interdisciplinary Study; Investigation; Keratitis; Late Effects; Libraries; Lipids; Mechlorethamine; Mediating; Melanins; MicroRNAs; Mustard; Mustard Gas; Names; Nanotechnology; Newsletter; Patient Care; Patients; Peptides; Pharmaceutical Preparations; Phase; Polymers; Positioning Attribute; Property; Recording of previous events; Regimen; Research; Research Personnel; Research Project Grants; Sampling; Schools; Science; Scientist; Services; Skin; Skin injury; Societies; Sunburn; Systemic Therapy; Technology; Testing; Therapeutic Uses; Topical application; Training and Education; Translational Research; Translations; Universities; Woman; archived data; boys; chemical threat; college; data archive; diversity and inclusion; efficacy evaluation; eye dryness; girls; immune activation; improved; in vivo; innovation; medical countermeasure; medical schools; multiple omics; nanolipoprotein particles; nanoparticle; nonhuman primate; novel; novel therapeutics; outreach; particle; programs; recruit; synergism; systemic intervention; therapeutic development; translational study; wound healing

Northwestern University (NU) is recognized for its strong interdisciplinary cutaneous, ocular, nanotechnology and immunology research programs with particular strength in investigations related to wound repair and inflammation. Leveraging these strengths, the theme of the NU CounterAct Center of Excellence (NUCCX) is the “Barrier Damage and The Immune Cascade”, with its goal to promote outstanding translational research in the treatment of sulfur mustard (SM) injury. The NUCCX, with its 12 senior research scientists, encompasses 7 University departments within the Feinberg Medical School and the Weinberg College of Arts and Sciences. Information generated through the NUCCX will improve patient care to those suffering from SM injury. To accomplish this goal, the NUCCX has the following Research Projects and Cores: (i) Topical and Systemic Interventions for Mustard-induced Skin Injury (Project 1); (ii) Reversing the Ocular Impact of NM and SM Through Novel Therapies (Project 2); (iii) Translation and Trials: Advancing Medical Countermeasure Development (Project 3); (iv) Administrative Core (Core A); (v) Lipid-Based Materials Synthesis and Characterization Core (Core B); (vi) Polymeric Materials Synthesis and Characterization Core (Core C); and (vii) Education and Enrichment Core (Core D). Project 1 will examine the clinical potential of systemically administered PLGA-IMPs in conjunction with vitamin D3 to mitigate immune activation following NM and SM skin exposure. A similar nanoparticle-based strategy will be used to evaluate reduction of skin inflammation with topical HDL NP and/or synthetic melanin PDA NP. Project 2 will define the clinical potential of topical HDL NP-based eye drops in the context of acute and delayed phases resulting from NM and SM exposure in the cornea. A similar approach will be taken to evaluate systemically administered vitamin D3 and PLGA-IMPs in ocular NM/SM injury. Project 3 will use non-invasive testing in humans to define the signature inflammatory biomarkers that will be evaluated in clinical trials testing of vitamin D3 and PLGA-IMP. The translational studies are highly relevant to mustard as they are based on multi-omics analysis data of archived skin samples from in vivo SM (non-human primate) and NM (human) mustard exposure. The Admin Core will be a focal point for all University-wide SM-related activities and will be responsible for coordinating all activities of the NUCCX. Core B will synthesize a suite of organic cores to be used as templates to produce a library of nanoparticles formulated to be topically applied to the eye and skin. Core C will synthesize synthetic melanin, polymer-peptide hybrid materials and PLGA-IMPs to be used for therapeutic development. Core D will foster education and training, as well as advance personal and professional development of NUCCX trainees and investigators. This Core will also promote inclusivity and diversity within the mustard injury field. Projects 1-3 and Cores A-D interdigitate with each other and have strong translational components. The NUCCX is well positioned to take basic findings into a clinical setting, which will facilitate our understanding and treating SM injury of the skin and eyes.

西北大学 (NU) 以其强大的跨学科皮肤、眼科、纳米技术而闻名 和免疫学研究项目，特别是与伤口修复相关的研究 利用这些优势，NU CounterAct 卓越中心 (NUCCX) 的主题是： “屏障损伤和免疫级联”，其目标是促进杰出的转化研究 NUCCX 拥有 12 名高级研究科学家，其中包括 7 名研究人员。 范伯格医学院和温伯格艺术与科学学院内的大学系。 通过 NUCCX 生成的信息将改善对 SM 损伤患者的护理。 为了实现这一目标，NUCCX 有以下研究项目和核心： (i) 主题和系统 芥末引起的皮肤损伤的干预措施（项目 1）；(ii) 通过逆转 NM 和 SM 对眼部的影响 新型疗法（项目 2）；(iii) 转化和试验：推进医疗对策的开发 （项目3）；（iv）行政核心（核心A）；（v）脂质材料合成和表征核心 （核心 B）；（vi）高分子材料合成和表征核心（核心 C）；以及（vii）教育和 丰富核心（核心 D）项目 1 将检查系统施用 PLGA-IMP 的临床潜力。 与维生素 D3 结合，可减轻 NM 和 SM 皮肤暴露后的免疫激活。 基于纳米颗粒的策略将用于评估局部 HDL NP 和/或对皮肤炎症的减少作用 合成黑色素 PDA NP 项目 2 将确定基于 HDL NP 的局部滴眼剂在眼科领域的临床潜力。 角膜中 NM 和 SM 暴露引起的急性期和延迟期的情况将采用类似的方法。 用于评估全身维生素 D3 和 PLGA-IMP 在眼 NM/SM 损伤中的作用 项目 3。 将使用人体非侵入性测试来定义标志性炎症生物标志物，这些标志物将在 维生素 D3 和 PLGA-IMP 的临床试验测试与芥末高度相关。 它们基于体内 SM（非人类灵长类动物）存档皮肤样本的多组学分析数据， NM（人类）芥末暴露将成为全校所有 SM 相关活动的焦点。 并将负责协调 NUCCX 的所有活动 Core B 将合成一套有机的。 核心用作模板来产生纳米粒子库，配制用于局部应用于眼睛 Core C将合成合成黑色素、聚合物-肽杂化材料和PLGA-IMP以供使用。 核心 D 将促进教育和培训，以及促进个人和发展。 NUCCX 学员和调查人员的专业发展也将促进包容性和 芥菜损伤领域内的多样性，项目 1-3 和核心 A-D 相互交叉，具有很强的多样性。 NUCCX 处于有利地位，可以将基本发现应用于临床环境，这将 有助于我们了解和治疗皮肤和眼睛的 SM 损伤。

项目成果

Vitamin D3 and deconvoluting a rash.

维生素 D3 和消除皮疹。

• 发表时间: 2023-01-24
• 影响因子: 8
• 作者: Ernst, Madison K;Evans, Spencer T;Techner, Jose;Rothbaum, Robert M;Christensen, Luisa F;Onay, Ummiye Venus;Biyashev, Dauren;Demczuk, Michael M;Nguyen, Cuong V;Honda, Kord S;McCormick, Thomas S;Tsoi, Lam C;Gudjonsson, Johann E;Cooper, Kev
• 通讯作者: Cooper, Kev