Pawel Ciborowski, PhD
Research Interests: Research in the Proteomics Laboratory is focused on the correlation of structure and function of proteins, their receptors and the impact of posttranslational modifications on their functions. Unlike genes, which all use the same code, each protein has unique physical properties, preventing attempts to develop a single method to study their structure and function in living organisms. Using state-of-the-art techniques in proteomics, we are investigating the structure and function of proteins which are involved in: (i) response to changes in cell's environment, (ii) response to stimuli such as tissue injury, infection, and drug treatment, and (iii) during malignant transformation. Our effort is to use proteomics approach in understanding molecular mechanisms of pathological processes and to apply this information in designing new strategies for disease prevention, early diagnosis, and control. There are three currently ongoing projects in the Proteomics Laboratory. Two of these projects are focused on changes in proteomes of human macrophages in response to HIV-1 infection. These studies will address the hypothesis that alterations in monocyte-derived macrophage (MDM) immunity occur as a consequence of HIV-1 infection permit the virus to persist in cells despite the macrophage's phagocytic, innate and adaptive immune responses. These studies will lead to identification of how cellular proteins are linked to the establishment of persistent viral replication in monocyte-derived macrophage (MDM) are regulated. Thus, to determine the potential pathways for how HIV-1 can bypass anti-viral intracellular immune responses, proteomic tests will be used to uncover protein fingerprints of HIV-1 infected MDM (in laboratory experiments using a panel of macrophage, lymphocyte, dual and neuro-tropic viral isolates) obtained from seronegative donors. The third project is focused on discovery of biomarkers of HIV-associated Neurocognitve Disorder (HAND) using CSF and plasma samples. Selected Recent Publications : 1. K.A. Carlson, P. Ciborowski, C. Schellpeper, T. M. Biskup, R.F. Shen, X. Luo, C. J. Destache, and H.E. Gendelman, Proteomic fingerprinting of HIV-1-infected human monocyte-derived macrophages: A preliminary report. J. Neuroimmunol. 2004, 147:35-42. 2. P. Ciborowski, Y. Enose, A. Mack, M. Fladseth, and H. Gendelman. Diminished matrix metalloproteinase 9 secretion in human immunodeficiency virus infected mononuclear phagocytes: modulation of innate immunity and implications for neurological disease. J. Neuroimmunol 2004, 157:11-16. 3. Y. Enose, C. Destache, A. Mack, J. Anderson, F. Ullrich, P. Ciborowski, and H. Gendelman. Proteomic Fingerprints Distinguish Microglia, Bone Marrow and Spleen Macrophage Populations. Glia. 2005, 51:161-172. 4. P. Ciborowski and H.E. Gendelman. Human Immunodeficiency Virus-Mononuclear Phagocyte Interactions: Emerging Avenues of Biomarker Discovery, Modes of Viral Persistence and Disease Pathogenesis. Current HIV Research, 2006, 4:279-291. 5. M. Ricardo-Dukelow, I. Kadiu-Kieken, W. Rozek, J. Schlautman, Y. Persidsky, P. Ciborowski, G. D. Kanmogne, H. E. Gendelman. HIV-1 infected monocyte-derived macrophages affect the human brain microvascular endothelial cell proteome: New insights into blood-brain barrier dysfunction for HIV-1-associated dementia. J. Neuroimmunol., 2007,185:37-46 6. P. Ciborowski, I. Kadiu, W. Rozek, K. Bernhardt, M. Fladseth, M. Ricardo-Dukelow, and H.E. Gendelman. The Human Immunodeficiency Type One-Infected Monocyte-Derived macrophage Secretome. Virology. 2007, 363:198-209. 7. J. G. Glanzner, E. Enose, T. Wang, I. Kadiu, N. Gong, W. Rozek, J. Liu, J. D. Shlautman, P. Ciborowski, M.P. Thomas, and H.E. Gendelman. Genomic and Proteomic Microglial Profiling: Pathways for Neuroprotective Inflammatory Responses Following Nerve Fragment Clearance and Activation, J. Neurochem., 2007, 102:627-645. 8. Kadiu, M. Ricardo-Dukelow, P. Ciborowski, and H. E. Gendelman. Cytoskeletal protein transformation in HIV-1 infected macrophage giant cells. J. Immunol., 2007, 178:6404-15. 9. W. Rozek, M. Ricardo-Dukelow, S. Holloway, V. Wojna, L. Melendez, and P. Ciborowski. Cerebrospinal fluid proteomic profiling of HIV-1-infected patients with or at risk for cognitive impairments. J. Proteome Res. 2007, 6:4189-99. 10. J. Perez Laspiur, E. Anderson, P. Ciborowski, V. Wojna. F. Duai, R. Mayo, E. Rodriguez, M. Plaud-Valentin, J. Rodriguez-Orengo, H.E. Gendelman, L.M. Melendez. CSF Proteomic Fingerprints for HIV-associated Cognitive Impairment. J Neuroimmunol. 2007, 192:157-70. 11. A. Reynolds, J. Glanzer, I. Kadiu, M. Ricardo-Dukelow, A. Chaudhuri, P. Ciborowski, R. Cerny, B. Gelman, M. P. Thomas, R. L. Mosley, and H. E. Gendelman. Nitrated alpha synuclein-activated microglial profiling for Parkinson’s disease. J Neurochem. 2008 104:1504-25. 12. W. Rozek and P. Ciborowski. Proteomics and Genomics. In: Neuroimmune Pharmacology, (H.E.Gendelman and T. Ikezu, eds.), Springer, Inc. 2008. 13. C. C. Caswell, R. Han, K. M. Hovis, P. Ciborowski, D. R. Keene, R. T. Marconi and S. Lukomski. Scl1 protein of M6-type group A Streptococcus binds the human complement regulatory protein, factor H, and inhibits the alternative pathway of complement. Mol Microbiol. 2008, 67:584-96. 14. E.J. Benner, R. Banerjee, A.D. Reynolds, S. Sherman, V.M. Pisarev, V. Tsiperson V, C. Nemachek, P. Ciborowski, S. Przedborski, R.L. Mosley, H.E. Gendelman. Nitrated alpha-Synuclein Immunity Accelerates Degeneration of Nigral Dopaminergic Neurons. PLoS ONE. 2008, 3(1):e1376. 15. A.D. Reynolds, I. Kadiu, S.K. Grag J. G. Glanzer, T. Nordgren, P. Ciborowski, R. Banerjee, and H.E. Gendelman. Nitrated Aplha-Synuclein and microglial neuroregulatory activities. J Neuroimmune Pharmacol. 2008, 3:59-74. 16. W. Rozek, J. Horning, J. Anderson, and P. Ciborowski. Sera Proteomic Biomarker Profiling in HIV-1 Infected Subjects with Cognitive Impairment. Proteomics – Clinical Applications, 2008, in press. 17. T. Wang, N. Gong, J. Liu, I. Kadiu, S. D. Kraft-Terry, R. L. Mosley, D. J. Volsky, P. Ciborowski, and H. E. Gendelman. Proteomic Modeling for HIV-1 Infected Microglia-Astrocyte Crosstalk. PLoS ONE. 2008, 3(6):e2507. 18. T. Wang, N. Gong, J. Liu, I. Kadiu, S. D. Kraft-Terry, J. D. Schlautman, P. Ciborowski, D. J. Volsky, and H. E. Gendelman. HIV-1 infected astrocytes and the microglial proteome. J. Neuroimmune Pharmacol. 2008, Jun 28. [Epub ahead of print]. 19. P. Ciborowski and H. Ali. Bioinformatics In: Proteomics for Undergraduates. A. Kraj and J. Silberring (eds.) Wiley Inc., 2008 – in press. 20. J. D. Schlautman, W. Rozek, R.L. Mosley, R. Stettler, H. E. Gendelman, and P. Ciborowski. Multidimensional Protein Fractionation Using ProteomeLab PF2D for Profiling Amyotrophic Lateral Sclerosis Immunity: A Preliminary Report. Proteome Science, 2008, in press.
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