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，纳米技术而闻名 和免疫学研究计划，在与伤口修复有关的研究方面具有特别的优势， 炎症利用这些优势，卓越的NU反行动中心（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， 硫芥（SM）损伤的治疗。NUCCX拥有12名高级研究科学家， Feinberg医学院和温伯格艺术与科学学院内的大学部门。 通过NUCCX生成的信息将改善SM损伤患者的护理。到 为了实现这一目标，NUCCX有以下研究项目和核心：（一）专题和系统 芥子气引起的皮肤损伤的干预措施（项目1）;（ii）通过 新疗法（项目2）;（iii）翻译和试验：推进医疗对策开发 （项目3）;（四）行政核心（核心A）;（五）脂基材料合成和表征核心 (Core B）;（vi）聚合物材料合成和表征核心（核心C）;以及（vii）教育和 浓缩核心（核心D）。项目1将检查全身给药PLGA-IMP的临床潜力 与维生素D3结合以减轻NM和SM皮肤暴露后的免疫激活。类似的 基于纳米颗粒的策略将用于评估局部HDL NP和/或 合成黑色素PDA NP。项目2将确定局部HDL NP滴眼液在美国的临床潜力。 角膜中NM和SM暴露导致的急性和延迟阶段的背景。类似的方法将 用于评价全身给予的维生素D3和PLGA-IMP在眼部NM/SM损伤中的作用。项目3 将在人体中使用非侵入性测试来定义将在临床上评估的标志性炎症生物标志物。 维生素D3和PLGA-IMP的临床试验测试。转化研究与芥末高度相关， 它们基于来自体内SM（非人灵长类动物）的存档皮肤样品的多组学分析数据， NM（人类）芥子气暴露。行政核心将成为所有全校SM相关活动的焦点 并将负责协调NUCCX的所有活动。核心B将合成一套有机 用作模板以产生配制成局部施用到眼睛的纳米颗粒库的核 和皮肤。核心C将合成合成黑色素、聚合物-肽杂化材料和PLGA-IMP 用于治疗发展。核心D将促进教育和培训，并促进个人和 NUCCX学员和调查员的专业发展。该核心还将促进包容性， 芥末伤害领域的多样性。项目1-3和核心A-D相互交叉， 平移分量NUCCX能够很好地将基本发现应用于临床， 有助于我们对皮肤和眼睛SM损伤的认识和治疗。

项目成果

Vitamin D3 and deconvoluting a rash.

• DOI: 10.1172/jci.insight.163789
• 发表时间: 2023-01-24
• 期刊: JCI INSIGHT
• 影响因子: 8
• 作者: Ernst, Madison K.;Evans, Spencer T.;Techner, Jose-Marc;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, Kevin D.;Lu, Kurt Q.
• 通讯作者: Lu, Kurt Q.