- Research Associate Professor, University of Notre Dame
- Research Assistant Professor, University of Notre Dame
- Applied Biosystems (AB Sciex), Mass-Spectrometry-Proteomics Group
- Ph.D. in Biochemistry, Texas A&M University
- B.S. in Microbiology, University of Iowa
We are primarily interested in developing and exploiting novel approaches to identify and characterize the components of secreted proteins from virulent microorganisms. We heavily utilize the 'awesome power of genetics' coupled with state-of-the art quantitative proteomics to enrich, identify and quantify the proteins responsible for biological phenotypes. We have ongoing projects in pathogenic mycobacteria, protein translation in E. coli through the PTRN, and quantitative protein secretion measured using capillary electrophoresis. One example is described below.
Mycobacteria, the causative agent of tuberculosis, like most organisms secretes proteins for biochemical functions. Secreted proteins are a proteome of 'target'-enriched material which contains virulence-factors, antigenic-determinants, and targets for treatment/detection. EsxA and EsxB (ESAT-6 and CFP10) are essential virulence factors exported by mycobacteria and other Gram positive pathogens. Identification of proteins that are required for effective synthesis and secretion of these crucial virulence determinants has been hindered by a lack of saturating genetic screens; high-throughput biochemical detection, and accurate quantification of disease phenotypes. We designed orthogonal antibody-free assays using a slew of proteogenetic approaches to comprehensively dissect the individual contribution of gene products towards a functioning disease secretion system (ESX-1) in pathogenic mycobacterium. This framework is highly extensible to the analysis of other pathogen and protein secretion systems, and has uncovered novel genes, pathways, and crosstalk among secretion systems.
- Nguyen, T.T., Ding, D., Wolter, W.R., Pérez, R.L., Champion, M.M., Mahasenan, K. V., Hesek, D., Lee, M., Schroeder, V.A., Jones, J. I., Lastochkin, E., Rose, M. K., Peterson, C. E., Suckow, M.A., Mobashery, S., Chang, M. "Validation of Matrix Metalloproteinase-9 (MMP-9) as a Novel Target for Treatment of Diabetic Foot Ulcers in Humans and Discovery of a Potent and Selective Small-Molecule MMP-9 Inhibitor That Accelerates Healing" 2018 Journal of Medicinal Chemistry, in press. DOI: 10.1021/acs.jmedchem.8b01005
- Feng, S., Cheng, X., Zhang, L., Lu, X., Chaudhary, S., Teng, R., Frederickson, C., Champion, M. M., Zhao, R., Cheng, L., Gong, Y., Deng, H., Lu, X. "Myeloid-derived suppressor cells inhibit T cell activation through nitrating LCK in mouse cancers" 2018 Proceedings of the National Academy of Sciences of the United States of America, 115 (40), pp. E10094-E10099. DOI: 10.1073/pnas.1800695115
- Thompson, C.R., Champion, M.M., Champion, P.A. "Quantitative N-Terminal Footprinting of Pathogenic Mycobacteria Reveals Differential Protein Acetylation" 2018 Journal of Proteome Research, 17 (9), pp. 3246-3258. DOI: 10.1021/acs.jproteome.8b00373
- Nguyen, T.T., Ding, D., Wolter, W.R., Champion, M.M., Hesek, D., Lee, M., Pérez, R.L., Schroeder, V.A., Suckow, M.A., Mobashery, S., Chang, M. "Expression of active matrix metalloproteinase-9 as a likely contributor to the clinical failure of aclerastide in treatment of diabetic foot ulcers" 2018 European Journal of Pharmacology, 834, pp. 77-83. DOI: 10.1016/j.ejphar.2018.07.014
- Bosserman, R.E., Nguyen, T.T., Sanchez, K.G., Chirakos, A.E., Ferrell, M.J., Thompson, C.R., Champion, M.M., Abramovitch, R.B., Champion, P.A. "WhiB6 regulation of ESX-1 gene expression is controlled by a negative feedback loop in Mycobacterium marinum" 2017 Proceedings of the National Academy of Sciences of the United States of America, 114 (50), pp. E10772-E10781. DOI: 10.1073/pnas.1710167114
- Peuchen, E.H., Cox, O.F., Sun, L., Hebert, A.S., Coon, J.J., Champion, M.M., Dovichi, N.J., Huber, P.W. "Phosphorylation Dynamics Dominate the Regulated Proteome during Early Xenopus Development" 2017 Scientific Reports, 7 (1), 15647. DOI: 10.1038/s41598-017-15936-y