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

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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.