Sealy Center for Molecular Medicine

Research Summary

The comparatively new field of differential proteomics promises the design and implementation of pharmacological, immunological, or other interventional strategies affecting the expression and function of proteins in human disease. In addition, it holds the promise of identification of protein/peptide biomarkers that will permit early diagnosis and prognosis of human disease. The unmet challenge implicit in these tasks involves the detection and quantification of the uniquely expressed proteins that represent less than 1% of the total number of proteins expressed and are very low in abundance (<1000 copies/cell).

My lab is engaged in a two-tiered research strategy: 1. the development of highly sensitive and automated technology to separate, quantify, and isolate uniquely expressed disease-relevant low-abundance proteins, and 2. the application of these technologies to the detection and identification of disease biomarkers, and low-abundance proteins that guide metabolism and signal transduction mechanisms. The latter involves deep proteome mining and identification and quantification of protein post-transcriptional/translational mechanisms (PTM), a particularly daunting challenge given that most of the proteome complexity of an organism is captured by PTMs that decorate its structure.

Differential proteomics thus holds significant promise to impact the clinical outcomes of many diseases, in particular the insidious forms of cancer, infectious disease, and the host's inflammatory response. Therefore, through collaboration with our clinical research colleagues, we are developing the tools to aid in the discovery and identification of proteins and their PTMs that impact their role as causative agents, leading to a better understanding of biological mechanisms, and as biomarkers for the diagnosis, staging, and prognosis of human disease.

Selected Publications

1. Wiktorowicz, J. E., Stafford, S., Rea, H., Urvil, P., Soman, K., Kurosky, A., Perez-Polo, J. R., and Savidge, T. C. (2011) Quantification of cysteinyl S-nitrosylation by fluorescence in unbiased proteomic studies. Biochemistry 50, 5601-14. 10.1021/bi200008b.


2. Wiktorowicz, J.E., Jamaluddin. M. Proteomic analysis of the asthmatic airway. (2014) Adv Exp Med Biol. 795, 221-32. doi: 10.1007/978-1-4614-8603-9_14. PMID: 24162912.


3. 3. Brasier AR†, Zhao Y†, Wiktorowicz JE†, Spratt HM†, Nascimento EJ, Cordeiro MT, Soman KV, Ju H, Recinos A 3rd, Stafford S, et al. (2015) Molecular classification of outcomes from dengue virus -3 infections. J Clin Virol. Mar;64:97-106. doi: 10.1016/j.jcv.2015.01.011. Epub 2015 Jan 17. PubMed PMID: 25728087; PubMed Central PMCID: PMC4346782. †Equal contributors


4. Garg, N.J.*, Soman, K.V., Zago, M.P., Koo, S-J., Spratt, H., Stafford, S., Blell, Z.N., Gupta, S., Burgos, J.N., Barrientos, N., Brasier, A.R., Wiktorowicz, J.E.* (2016) Changes in Proteome Profile of Peripheral Blood Mononuclear Cells in Chronic Chagas Disease. PLoS Negl Trop Dis 10(2): e0004490. doi:10.1371/journal. pntd.0004490. *Co-senior authors


5. Koo, S-J., Spratt, H.M., Soman, K.V., Stafford, S., Petersen, J.R., Gupta, S.J., Zago, M.P., Martinez, M.N., Brasier, A., Wiktorowicz, J.E.*, Garg, N.J.* (2016) S-Nitrosylation Proteome Profile of Peripheral Blood Mononuclear Cells in Human Heart Failure. Int. J. Proteomics, Article ID: 1384523, 1-19  (*Joint-corresponding/senior authors).


6. Szczesny, B., Marcatti, M., Zatarain, J.R., Druzhyna, N., Wiktorowicz, J.E., Nagy, P., Hellmich, M.R., Szabo, C., (2016). Inhibition of hydrogen sulfide biosynthesis sensitizes lung adenocarcinoma to chemotherapeutic drugs by inhibiting mitochondrial DNA repair and suppressing cellular bioenergetics. Scientific Reports. 6, 36125; doi:10.1038/srep36125.


7. Wiktorowicz, C.J., Arnold, B., Wiktorowicz, J.E., Murray, M.L., Kurosky, A. (2016) Hemorrhagic fever virus, human blood, and tissues in mortuary vessels from an Iron Age burial mound in Central Europe. J. Archeol. Sci. 78, 29–39. (Highlighted in “Latest News,” Science, http://www.sciencemag.org/news/2016/12/human-blood-organs-and-surprising-virus-detected-ancient-pottery).


8. Wiktorowicz, J. E., Soman, K.V. (2016) Discovery of Candidate Biomarkers. Adv Exp Med Biol. 919, 443-462. PMID: 2797523024162912.


9. Wiktorowicz, J.E., Stafford, S.J., Garg, N.J., (2017). Protein Cysteinyl-S-Nitrosylation: Analysis and Quantification. In Methods in Enzymology. Proteomics in Biology, Part B, Vol. 586, A.K. Shukla, ed.^eds. Academic Press, Burlington, UK, pp. 1-14.