This is a renewal application for the Rutgers University CounterACT Research Center of Excellence, which is focused on the discovery and development of drugs to treat poisoning from exposure to vesicants including sulfur mustard, nitrogen mustard, and other mechanistically related chemical threat agents. The Center consists of three Research and Development Projects, each focused on a major vesicant target: the skin, the cornea and the lung. The overall goal of the Center is to identify specific targets in these tissues that can be used for therapeutic intervention. To accomplish this goal, mechanistic research using appropriate models for the skin, cornea and lung is being performed by scientific experts in each of these areas. The Research and Development Projects are supported by a Pharmacology and Drug Development Scientific Support Core and a Pharmaceutics and Medicinal Chemistry Scientific Support Core, each consisting of investigators with considerable expertise in drug discovery, delivery and development. The Rutgers Center has discovered several efficacious lead compounds and developed innovative formulations and delivery systems that increase pharmacological activity and improve pharmacokinetic profiles. Two lead compounds, one for mustard- induced ocular injury and another for mustard-induced lung injury, are FDA approved for other uses, and are being advanced for use as mustard countermeasures. IND-enabling studies have been completed on a lead compound discovered to be effective against mustard-induced skin injury. The Rutgers CounterACT Center has established strategic corporate partnerships for advanced drug development with lead compounds and support by BARDA. A Research Education Core directed at students, postdoctoral trainees, technical staff, and new and established investigators has been highly successful and efforts will be expanded during the next grant period. Plans are to continue mechanistic research with the goal of identifying and developing second generation drug products with improved effectiveness. Current drug leads will also be advanced in the FDA approval process. It is anticipated that Center efforts will result in new drugs that will be in the advanced approval process for treating vesicant poisoning in humans.

Public Health Relevance

There is increasing concern that civilian populations might be exposed to chemical toxicants. The primary objective of the Center will be to develop medical countermeasures against these chemicals. A team of researchers has been assembled capable of rapid advancement of candidate drugs through the regulatory process, so that they can be used to enhance the medical response capabilities of the United States.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
2U54AR055073-11
Application #
9151413
Study Section
Special Emphasis Panel (ZRG1-MDCN-B (54)R)
Program Officer
Tseng, Hung H
Project Start
2006-09-15
Project End
2021-08-31
Budget Start
2016-09-22
Budget End
2017-08-31
Support Year
11
Fiscal Year
2016
Total Cost
$3,880,000
Indirect Cost
$1,153,151
Name
Rbhs-Robert Wood Johnson Medical School
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
078795875
City
Piscataway
State
NJ
Country
United States
Zip Code
08854
Chang, Yoke-Chen; Gordon, Marion K; Gerecke, Donald R (2018) Expression of Laminin 332 in Vesicant Skin Injury and Wound Repair. Clin Dermatol (Wilmington) 2:
Moretti, Alysha; Li, Qi; Chmielowski, Rebecca et al. (2018) Nanotherapeutics Containing Lithocholic Acid-Based Amphiphilic Scorpion-Like Macromolecules Reduce In Vitro Inflammation in Macrophages: Implications for Atherosclerosis. Nanomaterials (Basel) 8:
Szilagyi, John T; Fussell, Karma C; Wang, Yun et al. (2018) Quinone and nitrofurantoin redox cycling by recombinant cytochrome b5 reductase. Toxicol Appl Pharmacol 359:102-107
Joseph, Laurie B; Composto, Gabriella M; Perez, Roberto M et al. (2018) Sulfur mustard induced mast cell degranulation in mouse skin is inhibited by a novel anti-inflammatory and anticholinergic bifunctional prodrug. Toxicol Lett 293:77-81
Yang, Shaojun; Jan, Yi-Hua; Mishin, Vladimir et al. (2017) Diacetyl/l-Xylulose Reductase Mediates Chemical Redox Cycling in Lung Epithelial Cells. Chem Res Toxicol 30:1406-1418
Venosa, Alessandro; Gow, James G; Hall, LeRoy et al. (2017) Regulation of Nitrogen Mustard-Induced Lung Macrophage Activation by Valproic Acid, a Histone Deacetylase Inhibitor. Toxicol Sci 157:222-234
Francis, Mary; Sun, Richard; Cervelli, Jessica A et al. (2017) Editor's Highlight: Role of Spleen-Derived Macrophages in Ozone-Induced Lung Inflammation and Injury. Toxicol Sci 155:182-195
Chmielowski, Rebecca A; Abdelhamid, Dalia S; Faig, Jonathan J et al. (2017) Athero-inflammatory nanotherapeutics: Ferulic acid-based poly(anhydride-ester) nanoparticles attenuate foam cell formation by regulating macrophage lipogenesis and reactive oxygen species generation. Acta Biomater 57:85-94
Francis, Mary; Groves, Angela M; Sun, Richard et al. (2017) Editor's Highlight: CCR2 Regulates Inflammatory Cell Accumulation in the Lung and Tissue Injury following Ozone Exposure. Toxicol Sci 155:474-484
Malaviya, Rama; Laskin, Jeffrey D; Laskin, Debra L (2017) Anti-TNF? therapy in inflammatory lung diseases. Pharmacol Ther 180:90-98

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