The overall goal of our research program is to investigate the interactions of environmental chemicals with leukocytes including polymorphonuclear leukocytes, mononuclear cells and their bone marrow progenitors. Disease endpoints of interest include aplastic anemia, agranulocytosis, leukemia and increased susceptibility to infections and cancer. Agents whose chemico-biological interactions are under investigation include benzene, polycyclic aromatic hydrocarbons, lead and agricultural chemicals. In this regard, our studies are focused in three areas: the bioactivation and molecular interactions of xenobiotics of interest; the biochemical and molecular regulation of myelopoiesis and cell differentiation; and the development of in vitro and in vivo models to provide a mechanistic basis for risk assessment and to develop chemoprotective strategies for myeloid cell toxicity. In order to accomplish the goals of the program we employ a spectrum of analytic, biochemical and molecular approaches including the use of chemilumigenic probing for which the laboratory is noted. This technology is based on the assessment of reactive oxygen by organells and cells. In this regard, our recent studies focus on the assessment and regulation of reactive oxygen by mitochondria.

Faculty member of MIRTHE(Mid-InfraRed Technologies for Health and the Environment).MIRTHE is a National Science Foundation Engineering Research Center headquartered at Princeton University, with partners City College New York, Johns Hopkins University, Rice, Texas A&M, and the University of Maryland Baltimore County. The center encompasses a world-class team of engineers, chemists, physicists, environmental and bio-engineers, and clinicians. MIRTHE's goal is to develop Mid-Infrared (£ - 3-30 µm) optical trace gas sensing systems based on new technologies such as quantum cascade lasers or quartz enhanced photo-acoustic spectroscopy, with the ability to detect minute amounts of chemicals found in the environment or atmosphere, emitted from spills, combustion, or natural sources, or exhaled.

Through its fundamental research and prototyping in materials, sources, detectors, sensing systems, and applications testbeds, MIRTHE addresses a broad range of technologies and industry sectors - semiconductors, test and measurement, medical equipment manufacturers, chemical and petrochemical, and homeland security - as well as government labs and hospitals. MIRTHE provides interdisciplinary and practice oriented education for a diverse U.S. workforce and seeks to educate the public about chemical sensing with applications in environment, homeland security, and health. www.mirthecenter.org

Environmental Health Sciences, environmental chemicals, reactive oxygen,mitochondria, benzene, benzo(a)pyrene, leukocytes, polymorphonuclear leukocytes, mononuclear cells, bone marrow progenitors, aplastic anemia, agranulocytosis, leukemia,

2006 Johns Hopkins Diversity Award

NIGMS Pharmacology Research Associate Fellowship

CINE1996 award by the Council on Nontheatrical Events

The New York Festivals 1996 Finalist Award

Best paper in Toxicological Sciences, 2000.

Outstanding Faculty Service Award from the Interaction Community Outreach Program, Bloomberg School of Public Health, 2004

Trush, M.A., and LaPlant, J. The toxicology behind being green. Contracting Business ,65:36-37,2009

Zhu, H., Jia, Z., Misra,B.R., Zhang, L., Cao, Z., Yamamoto, H., Truah, M.A., Misra, H.P., and Li,Y. Nuclear factor E2-related Factor 2-dependent Myocardiac Cytoprotection Agains Oxidative and Electrophilic Stress. Cardiovasc.Toxicol.,2008

Zhu, H., Jia, Z., Zhang, L., Yamamoto, M., Misra, H.P., Trush, M.A., and Li, Y.Antioxidants and phase 2 enzymes in macrophages: regulation by Nrf2 signaling and protection against oxidative and electrophilic stress.Exp.Biol. Med.233:463-474, 2008.

Traore, K., Sharma, R., Thimmulappa, R.K., Watson, W.H., Biswal, S.and Trush, M.A. Redox-regulation of Erk1/2-directed phosphatase by reactive oxygen species: role in signaling TPA-induced growth arrest in ML-1 cells. J.Cell Physiol. 216:276-285,2008.

Sharma, R., Traore,K., Trush, M.A., and Burek, C.L.Intracellularadhesion molecule-1 up-regulation on thyrocytes by iodine of non-obese-diabetic.H2(h4)mice is reactive-oxygen species-dependent. Clin. Exp. Immunol.152:13-20,2008.

Cai,Z., Zhong,H.Bosch-Marce, M., Fox-Talbot,K.,Wang,L., Wei,C., Trush,M.A., and Smenza, G.L.Complete loss of ischemia preconditioningin mice with partial-deficiency of HIF-1 alpha. Cardiovasc.Res. 77:463-470,2008.

Jia, Z., Zhu, H., Trush, M.A., Misra, H.P., and Li, Y. Generation of superoxide from reaction of 3H-1,2-dithiole-3-thione with thiols :implications for dithiothione chemoprotection. Mol.Cell. Biochem. 307:185-191, 2008.

Thimmulappa, R.K., Fuchs, R.J., Malhotra, D., Scollick, C.Traore, K., Bream, J.H., Trush, M.A., Liby, K.T., Sporn, M.B., Kensler, T.W., and Biswal, S. Preclinical evaluation of targeting the Nrf2pathway by triterpenoids(CDDO-Im and CDDO-Me) for protection from LPS-induced inflammatory response and reactive oxygen species in human peripheral blood mononuclear cells and neutrophils. Antiox . Redox Signal.9:1963-1970, 2007.

Zhu, H., Jia, Z., Mahaney , J. E., Ross, D., Misra, H. P., Trush, M.A., and Li, Y.The highly expressed and inducible NAD(P)H :quinine oxidoreductase1 in cardiovascular cells acts as a potential superoxide scavenger. Cardiovasc. Toxicol. 7:202-211, 2007.

Zhu, H., Cao, Z., Zhang, L., Trush, M.A., and Li, Y. Glutathione and glutathione-linked enzymes in normal aortic smooth muscle cells: chemical inducibility and protection against reactive oxygen and nitrogen-species –induced injury. Mol. Cellular Biochem., 301:49-57 2007.

Zhu, H., Zhang, L., Trush , M.A., and Li, Y. Upregulation of endogenous glutathione system by 3H-1,2-dithiole-3-thione- in pancreatic RINm5Fbeta –cells as a novel strategy for protecting against oxidative beta –cell injury, Free Radical Res., 41:242-250, 2007.

Traore, K., Sharma, R., Burek, C.L., and Trush, M.A. Role of ROS in TPA-induced ICAM-1 expression in the myeloid ML-1 cell line , J. Cellular Biochemistry,100:1010-1021,2007.

Thimmulappa, R.K., Scollick, C., Traore, K., Yates, M., Trush, M.A., Liby, K.T., Sporn, M.B., Yamamoto, M., Kensler, T.W., Biswal, S. Nrf-2dependent protection from LPS induced inflammatory response and mortality by CDDO-imidazolide. Biochem. Biophys. Res. Commun. 35:883-889, 2006.

Osburn, W.O., Wakabayashi, N., Misra, V., Nilles, T., Biswal, S., Trush, M.A., and Kensler, T.W. Nrf2 regulates an adaptive response protecting against oxidative damage following diquat-mediated formation of superoxide anion. Arch. Biochem.Biophys., 454:7-15 ,2006

Novitskiy, G, Traore, K., Wang, L., Trush, M.A., and Mezey, E. effects of ethanol and acetaldehyde on reactive oxygen species in rat hepatic stellate cells. Alcoholism: Clinical and Experimental Res. 30:1429-1435, 2006.

Roseborough, G., Gao, D., Chen, L., Trush, M.A., Zhou, S., Williams, G.M., and Wei, C. The mitochondrial K-ATPase opener, diazoxide, prevents ischemia-reperfusion injury in rabbit spinal cord. Amer. J. Pathol., 168:1443-1451, 2006.

McGowan, J., Chen, L., Gao, D., Trush, M. and Wei , C. Increased mitochondrial reactive oxygen species production in newborn brain during hypoglycemia, Neuroscience Letters,399:111-114 , 2006.

Davis-McQuire, L., Zhengtong, P., Trush, M.A. Cheskin, L., Contoreggi, C., McCullough, K., Watkins, P.A., and Moran, T. Bromocriptine reduces steatosis in obese rodent models. J. Hepatology, 45:439-444, 2006.

Zhu, H., Zhang, L., Itoh, K., Yamamoto, M., Ross, D., Trush, M.A., Zweier, J.L., and Li, Y. Role of Nrf2 in controlling bone marrow stromal cell susceptibility to oxidative and electrophilic stress. Free Radical Biology Medicine, 41:132-143, 2006.

Luo, L.Chen, H., Trush , M.A., Show, M.D. and Zirkin, B.R. Aging and the brown Norway rat leydig cell antioxidant defense system. J. Androl. 27:240-247, 2006.

Li, Y., Cao, Z., Zhu, H., and Trush, M.A. Differential roles of 3H-1, 2-3-thione-induced glutathione, glutathione S-transferase and aldose reductase in protecting against 4-hydroxy-2-nonenal toxicity in cultured cardiomyocytes. Arch. Biochem. Biophysics, 439:80-90, 2005.

Traore, K., Trush, M. A., George, M. Jr., Spannhake,E. W., Anderson, W., and Asseffa, A. Signal transduction of phorbal 12-myristate 13-acetate(PMA)-induced growth inhibition of monocytic leukemia THP-1cells is reactive oxygen dependent, Leukemia Research , 29:863-879 , 2005.

Chou, W-C., Jie, C., Kenedy, A., Jones, R., Trush, M.A. and Dang, C-V. Role of NADPH oxidase in arsenic-induced reactive oxygen species formation and cytotoxicity in myeloid leukemia cells, Proc. Natl. Acad. Sci.USA 101-4578-4583 , 2004.

Chin, B.Y., Trush, M.A., Choi, A.M.and Risby, T.H. Transcriptional regulation of the heme oxygenase 1 gene in cultured macrophages exposed to model airborne particulate matter. Amer. J. Physiol. Lung Cellular and Molecular Physiology, 248:2473-2480, 2003.

Deng, X., Cai, N-S., McCoy, J.T., Chen,-W., Trush, M.A. and Cadet, J.L. Methamphetamine induces apoptosis in an immortalized rat striatal cell line by activating the mitochondrial cell death pathway, Neuropharmacology, 42:837-845, 2002.

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Trush, M.A. and Li, Y. Avoiding the jaws of using lucigenin as a chemiluminigenic probe for biological superoxide: Determining when its safe to go back into the water. In: Luminescence Biotechnology: Instruments and Applications, Van Dyke, K., Van Dyke C and Woodfork, K., (Eds). CRC Press, Boca Raton, FL, pp. 287-304, 2002.

Stansbury, K.H., Noll, D.M., Groopman, J.D. and Trush, M.A. Enzyme-mediated dialdehyde formation: An alternative pathway for benzo[a]pyrene-7,8-dihydrodiol bioactivation. Chem. Res. Toxicol., 13:1174-1180, 2000.

Bolton, J.L., Trush, M.A., Penning, T.M., Dryhurst, G. and Monks, T.J. 2000. Role of quinones in toxicology. Chem. Res. Toxicol., 13:135-160.

Li, X., Zhu, H. and Trush, M.A. 1999. Lucigenin and luminol as chemilumigenic probes for detecting oxygen species production by isolated mitochondria. Biochem. Biophys. Acta, 1428:1-12.

Li, Y., Zhu, H., Kuppusamy, P., Rouband, V, Zweier, J.L. and Trush, M.A. Validation of lucigenin as a chemilumigenic probe for detecting superoxide. J. Biol. Chem., 273:2015-2023, 1998.

mtrush@jhsph.edu