Biosketch:
Dr. Chung received Ph.D. from Seoul National University, South Korea, in 1996, and trained in National Heart, Lung, and Blood Institute/National Institutes of Health, Bethesda, MD, as postdoctoral and research fellow from 1999 to 2005. Since 2005, he has been working in NCBID, George Mason University. In this center, he have isolated secreted proteases in the culture supernatants of Bacillus anthracis and characterized them in terms of their pathological effects. He has a broad background in microbiology and biochemistry, with specific training and expertise in Gram-positive bacteriology. At George Mason University, he accomplished several projects including; the US Department of Defense grant (DAMD 17-03-C-01220) and the US Department of Energy grant (DE-FC52-FC04NA25455) for anthrax proteases and anthrax biomarkers, respectively.
Research Interests:
Host-pathogen interaction, Microbial pathogenesis, Innate immunity, Biomarkers of infectious diseases, Mixed infection, and Exosomes (miRNA and proteins)
Research Program:
Bacillus anthracis is the causative agent of anthrax in humans and animals. Human infection occurs when endospores enter the body by ingestion, inhalation, or through abrations in the skin. In lethal systemic anthrax, growing bacteria produce large quantities of the toxins lethal factor (LF) and edema factor (EF) that causes widespread vascular leakage and shock. Dr. Chung’s laboratory identified secreted metalloproteases InhA and NprB as candidate virulence factors. These proteases were further studied with specific emphasis on penetration of the blood-brain barrier, adhesion and invasion of vegetative bacteria, and regulation of blood chemistry (i.e. blood coagulation and fibrinolysis) in vitro and in mice.
The second major focus of Chung’s laboratory is directed at defining the mechanisms of B. anthraicis-derived nitric oxide (bNO), with a special emphasis on protein S-nitrosylation in infected macrophages, endothelial and epithelial cells. We have found a novel mechanism of host cell killing by the bNO-mediated mitochondrial impairment; in addition to the previously proposed mechanism involving LT in macrophages. A further study with human small airway epithelial cells suggested that B. anthracis infection produces NO in culture supernatants, resulting in protein S-nitrosylation of proteins involved in oxidative stress (i.e. peroxiredoxin 1) and inflammatory response (i.e. surfactant protein D).
More recently, the laboratory has focused on microRNAs (miRNAs) and proteins of exosomes purified from bacterial pathogen-infected cells. Exosomes are the newest family member of ‘bioactive vesicles’ that function to promote intercellular communication. Communication by exosomes is achieved by delivering proteins and miRNAs to distant recipient cells. The laboratory is examining whether exosomes are released by Yersinia pestis- or Bacillus anthracis-infected cells as an intercellular communicator, aiming to compare the profiles for gram-negative and gram-positive agents. These studies will open new directions in biomedical research.
Selected Publications
1. Chung M.C.*, S.C. Jorgensen, J.H. Tonry, F. Kashanchi, C. Bailey and S. Popov. Secreted Bacillus anthracis Proteases Target the Host Fibrinolytic System. FEMS Immunol Med Microbiol 62: 173–181, 2011.
2. Chung M.C.*, J. H. Tonry, A. Narayanan, N. P. Manes, R.S. Mackie, B. Gutting, D.V. Mukherjee, T.G. Popova, F. Kashanchi, C.L. Bailey, and S. G. Popov. Bacillus anthracis Interacts with Plasmin(ogen) to Evade C3b-dependent Innate Immunity. PLoS ONE 6(3): e18119, 2011.
3. Mukherjee DV, Tonry JH, Kim KS, Ramarao N, Popova TG, Bailey C, Popov SG*, and Chung MC*. Bacillus anthracis metalloprotease InhA induces blood-brain barrier permeability and contributes to cerebral hemorrhages. PLoS ONE 6(3): e17921, 2011.
4. Popova TG, Millis B, Chung MC, Bailey C, Popov SG. Anthrolysin O and fermentation products mediate the toxicity of Bacillus anthracis to lung epithelial cells under microaerobic conditions. FEMS Immunol Med Microbiol. 61(1):15-27, 2011.
5. Chung M.C., Jorgensen S. C., Popova T. G., Tonry J. H., Bailey C. L. and Popov S. G. Activation of plasminogen activator inhibitor implicates protease InhA in the acute-phase response to Bacillus anthracis infection. J. Med. Microbiol. 58: 737-744, 2009.
6. Bradburne C., Chung M.C., Zong Q., Schlauch K., Liu D., Popova T.G., Popova A.S., Bailey C., Soppet D., and Popov S.G. Transcriptional and apoptotic responses of THP-1 cells to challenge with toxigenic, and non-toxigenic Bacillus anthracis. BMC Immunol. 9: 67, 2008.
7. Chung M.C., Jorgensen S.C., Popova T.G., Bailey C.L. and Popov S.G. Neutrophil elastase and syndecan shedding contribute to antithrombin depletion in murine anthrax. FEMS Immunol. Med. Microbiol., 54: 309-318, 2008.
8. Chung M. C, Popova T. G, Jorgensen S. C, Dong L, Chandhoke V, Bailey C. L, Popov S. G. Degradation of circulating von Willebrand factor and its regulator ADAMTS13 implicates secreted Bacillus anthracis metalloproteases in anthrax consumptive coagulopathy. J. Biol. Chem. 283: 9531-9542, 2008
9. Chung, M. C, T. G. Popova, B. A. Millis, D. V. Mukherjee, W. Zhou, L. A. Liotta, E. F. Petricoin, V. Chandhoke, C. Bailey, and S. G. Popov. Secreted Neutral Metalloproteases of Bacillus anthracis as Candidate Pathogenic Factors. J. Biol. Chem. 281: 31408-31418, 2006.
10. Chung, M. C., & S. Kawamoto. IRF-2 is involved in up-regulation of the nonmuscle myosin heavy chain II-A gene expression during phorbol ester-induced promyelocytic HL-60 differentiation. J. Biol. Chem. 279: 56042-56052, 2004.
11. Chung, M. C., H. K. Kim & S. Kawamoto. TFEC can function as a transcriptional activator of the nonmuscle myosin II heavy chain-A gene in transfected cells. Biochemistry 40: 8887-8897, 2001.