U54AR079795

Barrier Damage and the Immune Cascade

Northwestern University CounterACT Center of Excellence (NUCCX) - 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 "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 for 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)
(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 the 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.

Northwestern University

THE NATIONAL INSTITUTE OF AND MUSCULOSKELETAL AND SKIN DISEASES (NIAMS) MISSION IS TO SUPPORT RESEARCH INTO THE CAUSES, TREATMENT, AND PREVENTION OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES, TRAINING OF BASIC AND CLINICAL SCIENTISTS TO CARRY OUT THIS RESEARCH, AND DISSEMINATION OF INFORMATION ON RESEARCH PROGRESS IN THESE DISEASES. THE EXTRAMURAL PROGRAM PROMOTES AND SUPPORTS BASIC, TRANSLATIONAL, AND CLINICAL STUDIES OF SYSTEMIC RHEUMATIC AND AUTOIMMUNE DISEASES, SKIN BIOLOGY AND DISEASES, BONE BIOLOGY AND DISEASES, MUSCLE BIOLOGY AND DISEASES, AND JOINT BIOLOGY AND DISEASES AND ORTHOPAEDICS. NIAMS SYSTEMIC RHEUMATIC AND AUTOIMMUNE DISEASES PROGRAMS ADDRESS BASIC, TRANSLATIONAL, AND CLINICAL RESEARCH, INCLUDING CLINICAL TRIALS AND OBSERVATIONAL AND MECHANISTIC STUDIES, FOCUSED ON IMMUNE-MEDIATED ARTHRITIS AND AUTOIMMUNE-RELATED ACUTE AND CHRONIC DISORDERS IN ADULTS AND CHILDREN. NIAMS SKIN BIOLOGY AND DISEASES PROGRAMS SUPPORT BASIC, TRANSLATIONAL, AND CLINICAL RESEARCH IN SKIN, INCLUDING BOTH COMMON AND RARE SKIN DISEASES. THESE PROGRAMS INCLUDE INVESTIGATIONS OF THE BASIC MOLECULAR, CELLULAR, AND DEVELOPMENTAL BIOLOGY OF SKIN, AS WELL AS STUDIES OF SKIN AS AN IMMUNE, SENSORY, ENDOCRINE, AND METABOLIC ORGAN. NIAMS BONE BIOLOGY AND DISEASES PROGRAMS SUPPORT RESEARCH ON THE CONTROL OF BONE FORMATION, RESORPTION, AND MINERALIZATION AS WELL AS THE EFFECTS OF SIGNALING MOLECULES ON BONE CELLS. THEY SUPPORT CLINICAL STUDIES OF INTERVENTIONS TO PREVENT FRACTURES ASSOCIATED WITH OSTEOPOROSIS AND RESEARCH INTO LESS COMMON BONE DISEASES. NIAMS MUSCLE BIOLOGY AND DISEASES PROGRAMS ENCOURAGE RESEARCH ON MUSCLE DEVELOPMENTAL BIOLOGY, GROWTH, MAINTENANCE, AND HYPERTROPHY, PHYSIOLOGY OF CONTRACTION, STRUCTURAL BIOLOGY OF THE CONTRACTILE APPARATUS, DISEASE MECHANISMS, BIOMARKERS AND OUTCOME MEASURES, AND DEVELOPMENT AND CLINICAL TESTING OF THERAPIES FOR CONDITIONS INCLUDING THE MUSCULAR DYSTROPHIES. NIAMS JOINT BIOLOGY, DISEASES, AND ORTHOPAEDICS PROGRAMS SUPPORT A BROAD SPECTRUM OF RESEARCH CENTERED ON THE INTERPLAY AMONG THE BODY'S MUSCLES, BONES, AND CONNECTIVE TISSUES. THEY ENCOURAGE TISSUE ENGINEERING AND REGENERATIVE MEDICINE RESEARCH, MOLECULAR BIOLOGY, IMAGING, AND CLINICAL RESEARCH, AND THE TREATMENT AND PREVENTION OF ORTHOPAEDIC CONDITIONS. NIAMS PARTICIPATES IN THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) AND SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAMS. THE SBIR PROGRAM IS INTENDED TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE STTR PROGRAM IS INTENDED TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.310 - Trans-NIH Research Support

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [HHS - NIH]

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Illinois United States

State-Wide

Countermeasures Against Chemical Threats (CounterACT) Research Centers of Excellence (U54 Clinical Trial Optional) (PAR-18-657)

Amendment Since initial award the End Date has been extended from 07/31/25 to 07/31/26 and the total obligations have increased 1092890900% from $1 to $10,928,910.