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Dr. Michael Trush

Ph.D.
Categories

Cancer Prevention and Control

Titles

Professor of Environmental Health Sciences,The Johns Hopkins Bloomberg School of Public Health
Joint Appointment in Oncology

Schools\Degrees

B.S./M.S.- California University, California, PA Ph.D.- West Virginia University, Morgantown, WV

Training

Fellow/Senior Staff Fellow- National Cancer Institue, NIH, Bethesda, MD
Fellow- Johns Hopkins Bloomberg School of Public Health

Research Summary

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. 

Journal Citations

Osburn, W.O.; Wakabayashi, N.; Misra, V.; Nilles, T.; Biswal, S.; Trush, M.A.; Kensler, T.W. Nrf2 regulates an adaptive response protecting against oxidative damage following diquat-mediated formation of superoxide anion. Arch Biochem Biophys. 2006 Oct 1;454(1):7-15.

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. Nrf2-dependent protection from LPS induced inflammatory response and mortality by CDDO-Imidazolide. Biochem Biophys Res Commun. 2006 Dec 29;351(4):883-889.

Zhu, H.; Zhang, L.; Itoh, K.; Yamamoto, M.; Ross, D.; Trush, M.A.; Zweier, J.L.; Li, Y. Nrf2 controls bone marrow stromal cell susceptibility to oxidative and electrophilic stress. Free Radic Biol Med. 2006 Jul 1;41(1):132-143.

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.; Biswal, S. Preclinical evaluation of targeting the Nrf2 pathway 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. Antioxid Redox Signal. 2007 Nov;9(11):1963-1970.

Traore, K.; Sharma, R.B.; Burek, C.L.; Trush, M.A. Role of ROS and MAPK in TPA-induced ICAM-1 expression in the myeloid ML-1 cell line. J Cell Biochem. 2007 Mar 1;100(4):1010-1021.

Zhu, H.; Cao, Z.; Zhang, L.; Trush, M.A.; Li, Y. Glutathione and glutathione-linked enzymes in normal human aortic smooth muscle cells: chemical inducibility and protection against reactive oxygen and nitrogen species-induced injury. Mol Cell Biochem. 2007 Jul;301(1-2):47-59.

Zhu, H.; Jia, Z.; Mahaney, J.E.; Ross, D.; Misra, H.P.; Trush, M.A.; Li, Y. The highly expressed and inducible endogenous NAD(P)H:quinone oxidoreductase 1 in cardiovascular cells acts as a potential superoxide scavenger. Cardiovascular toxicology. 2007;7(3):202-211.

Zhu, H.; Zhang, L.; Trush, M.A.; Li, Y. Upregulation of endogenous glutathione system by 3H-1,2-dithiole-3-thione in pancreatic RINm5F beta-cells as a novel strategy for protecting against oxidative beta-cell injury. Free radical research. 2007 Feb;41(2):242-250.

Cai, Z.; Zhong, H.; Bosch-Marce, M.; Fox-Talbot, K.; Wang, L.; Wei, C.; Trush, M.A.; Semenza, G.L. Complete loss of ischaemic preconditioning-induced cardioprotection in mice with partial deficiency of HIF-1 alpha. Cardiovascular research. 2008 Feb 1;77(3):463-470.

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

Sharma, R.; Traore, K.; Trush, M.A.; Rose, N.R.; Burek, C.L. Intracellular adhesion molecule-1 up-regulation on thyrocytes by iodine of non-obese diabetic.H2(h4) mice is reactive oxygen species-dependent. Clinical and experimental immunology. 2008 Apr;152(1):13-20.

Zhu, H.; Jia, Z.; Zhang, L.; Yamamoto, M.; Misra, H.P.; Trush, M.A.; Li, Y. Antioxidants and phase 2 enzymes in macrophages: regulation by Nrf2 signaling and protection against oxidative and electrophilic stress. Experimental biology and medicine (Maywood, NJ. 2008 Apr;233(4):463-474.

Rangasamy, T.; Williams, M.A.; Bauer, S.; Trush, M.A.; Emo, J.; Georas, S.N.; Biswal, S. Nrf2 Inhibits the Maturation of Murine Dendritic Cells by Ragweed Extract. Am J Respir Cell Mol Biol. 2009 Oct 5.

Rangasamy, T.; Williams, M.A.; Bauer, S.; Trush, M.A.; Emo, J.; Georas, S.N.; Biswal, S. Nuclear erythroid 2 p45-related factor 2 inhibits the maturation of murine dendritic cells by ragweed extract. Am J Respir Cell Mol Biol. 2010 Sep;43(3):276-285.



Jia, Z., H. Zhu, M. A. Trush, H. P. Misra, and Y. Li. 2008. Generation of superoxide from reaction of 3H-1,2-dithiole-3-thione with thiols: implications for dithiolethione chemoprotection. Mol Cell Biochem 307:185-91.



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



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



Luo, L., Chen, H., Trush, M. A., Show, M. D., Anway, M. D. & Zirkin, B. R. (2006). Aging and the brown Norway rat leydig cell antioxidant defense system. J Androl 27, 240-7.



Novitskiy, G., Traore, K., Wang, L., Trush, M. A. & Mezey, E. (2006). Effects of ethanol and acetaldehyde on reactive oxygen species production in rat hepatic stellate cells. Alcohol Clin Exp Res 30, 1429-35.



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



Roseborough, G., Gao, D., Chen, L., Trush, M. A., Zhou, S., Williams, G. M. & Wei, C. (2006). The mitochondrial K-ATP channel opener, diazoxide, prevents ischemia-reperfusion injury in the rabbit spinal cord. Am J Pathol 168, 1443-51.



Sharma, R., Traore, K., Trush, M.A., Rose, N.R., and Burek, C.L. (2008). Intracellular adhesion 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.



Thimmulappa, R. K., R. J. Fuchs, D. Malhotra, C. Scollick, K. Traore, J. H. Bream, M. A. Trush, K. T. Liby, M. B. Sporn, T. W. Kensler, and S. Biswal. 2007. Preclinical evaluation of targeting the Nrf2 pathway 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. Antioxid Redox Signal 9:1963-70.



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. (2006). Nrf2-dependent protection from LPS induced inflammatory response and mortality by CDDO-Imidazolide. Biochem Biophys Res Commun 351, 883-9.



Traore, K., R. B. Sharma, C. L. Burek, and M. A. Trush. 2007. Role of ROS and MAPK in TPA-induced ICAM-1 expression in the myeloid ML-1 cell line. J Cell Biochem 100:1010-21.



Traore, K., Sharma, R. B., Burek, C. L. & Trush, M. A. (2006). Role of ROS and MAPK in TPA-induced ICAM-1 expression in the myeloid ML-1 cell line. J Cell Biochem.



Traore, K., Trush, M. A., George, M., Jr., Spannhake, E. W., Anderson, W. & Asseffa, A. (2005). Signal transduction of phorbol 12-myristate 13-acetate (PMA)-induced growth inhibition of human monocytic leukemia THP-1 cells is reactive oxygen dependent. Leuk Res 29, 863-79.



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



Zhu, H., L. Zhang, M. A. Trush, and Y. Li. 2007. Upregulation of endogenous glutathione system by 3H-1,2-dithiole-3-thione in pancreatic RINm5F beta-cells as a novel strategy for protecting against oxidative beta-cell injury. Free Radic Res 41:242-50.



Zhu, H., Z. Cao, L. Zhang, M. A. Trush, and Y. Li. 2007. Glutathione and glutathione-linked enzymes in normal human aortic smooth muscle cells: chemical inducibility and protection against reactive oxygen and nitrogen species-induced injury. Mol Cell Biochem 301:47-59.



Zhu, H., Z. Jia, J. E. Mahaney, D. Ross, H. P. Misra, M. A. Trush, and Y. Li. 2007. The highly expressed and inducible endogenous NAD(P)H:quinone oxidoreductase 1 in cardiovascular cells acts as a potential superoxide scavenger. Cardiovasc Toxicol 7:202-11.



Zhu, H., Zhang, L., Itoh, K., Yamamoto, M., Ross, D., Trush, M. A., Zweier, J. L. & Li, Y. (2006). Nrf2 controls bone marrow stromal cell susceptibility to oxidative and electrophilic stress. Free Radic Biol Med 41, 132-43.



Cao, Z., Hardey, D., Trombetta, L. D., Trush, M. A., & Li, Y. 2003. Induction of cellular glutathione and glutathione S-transferase by 3H-1,2-dithole-3-thione in rat aortic smooth muscle A 10 cells: protection against acrolein-induced toxicity. Atherosclerosis. 166:291-301.



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



Chou, W. C., Jie, C., Kenedy, A., Jones, R., Trush, M. A., & Dang, C. V. 2004. 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.



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



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



Trush, M. A., & Li, Y. 2002. Avoiding the jaws of using lucigenin as a chemiluminigenic probe for biological superoxide: determining when it's safe to go back into the water. In K. Van Dyke, C. Van Dyke, & K. Woodfork (Eds.), Luminescence biotechnology: instruments and applications (pp. 287-304). FL: CRC Press LLC.

 

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