This is a renewal application for the UMDNJ/Rutgers University CounterACT Research Center of Excellence, which is specifically 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 eye, lung and skin. Research is centered on elucidating specific mechanisms of vesicant toxicity, with the overall goal of identifying targets for therapeutic intervention. These projects are supported by a Pharmacology and Drug Development Core and a Medicinal Chemistry and Pharmaceutics Core consisting of investigators with considerable expertise in drug discovery, delivery and development. Important lead compounds have been identified and innovative formulations and delivery systems developed that increase pharmacological activity and improve pharmacokinetic profiles. Over 150 potential therapeutic compounds were synthesized, formulated, and evaluated for efficacy in vitro and against vesicant-induced injury resulting in four distinct families that will be chemically optimized during the renewal period. A Training and Education Program has been established directed at students, postdoctoral fellows and health care providers at the Universities of CounterACT investigators. During the next grant period, mechanistic research will focus on following novel discoveries related to how vesicants damage tissues including studies on autophagy, matrix metalloproteinases, ER stress proteins, and the role of macrophage subpopulations. The Pharmacology and Drug Development Core will continue to have informal meetings with the FDA, conduct IND-enabling studies, coordinate activities with external collaborators;it will also evaluate and advance selected lead compounds. The Medicinal Chemistry and Pharmaceutics Core will chemically optimize lead compounds in four promising classes, as well as develop strategies and targeted delivery systems to support multiple agent/ multiple mechanism treatment regimes for vesicant-mediated wound healing. It is anticipated that Center efforts will result in new drugs that will be in the 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.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZRG1-MDCN-J (54))
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Tseng, Hung H
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University of Medicine & Dentistry of NJ
Public Health & Prev Medicine
Schools of Medicine
United States
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Lasfar, Ahmed; de la Torre, Andrew; Abushahba, Walid et al. (2016) Concerted action of IFN-α and IFN-λ induces local NK cell immunity and halts cancer growth. Oncotarget :
Composto, Gabriella M; Laskin, Jeffrey D; Laskin, Debra L et al. (2016) Mitigation of nitrogen mustard mediated skin injury by a novel indomethacin bifunctional prodrug. Exp Mol Pathol 100:522-31
Gordon, Marion K; DeSantis-Rodrigues, Andrea; Hahn, Rita et al. (2016) The molecules in the corneal basement membrane zone affected by mustard exposure suggest potential therapies. Ann N Y Acad Sci 1378:158-165
Udasin, Ronald G; Wen, Xia; Bircsak, Kristin M et al. (2016) Nrf2 Regulates the Sensitivity of Mouse Keratinocytes to Nitrogen Mustard via Multidrug Resistance-Associated Protein 1 (Mrp1). Toxicol Sci 149:202-12
Francis, Mary; Sun, Richard; Cervelli, Jessica A et al. (2016) Role of Spleen-derived Macrophages in Ozone-Induced Lung Inflammation and Injury. Toxicol Sci :
Weinberger, Barry; Malaviya, Rama; Sunil, Vasanthi R et al. (2016) Mustard vesicant-induced lung injury: Advances in therapy. Toxicol Appl Pharmacol 305:1-11
Businaro, Rita; Corsi, Mariangela; Di Raimo, Tania et al. (2016) Multidisciplinary approaches to stimulate wound healing. Ann N Y Acad Sci 1378:137-142
Venosa, Alessandro; Malaviya, Rama; Choi, Hyejeong et al. (2016) Characterization of Distinct Macrophage Subpopulations during Nitrogen Mustard-Induced Lung Injury and Fibrosis. Am J Respir Cell Mol Biol 54:436-46
Mandal, Mili; Gardner, Carol R; Sun, Richard et al. (2016) The spleen as an extramedullary source of inflammatory cells responding to acetaminophen-induced liver injury. Toxicol Appl Pharmacol 304:110-20
Jan, Yi-Hua; Richardson, Jason R; Baker, Angela A et al. (2016) Novel approaches to mitigating parathion toxicity: targeting cytochrome P450-mediated metabolism with menadione. Ann N Y Acad Sci 1378:80-86

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