Director, Mass Spectometry and Proteomics Core Facility
Durham Research Center 3048
985800 Nebraska Medical Center
Omaha, NE 68198-5800
E-mail: Pawel Ciborowski
Keywords: proteomics, macrophage, HIV-1, drugs of abuse, biomarkers, histones, bioinformatics
V International Congress on Analytical Proteomics 2017
One of the Keynote Speakers -- Pawel Ciborowski, Ph.D.
UNMC Newsroom | May 21, 2012
Meet UNMC Distinguished Scientist Pawel Ciborowski, Ph.D.
2nd International Conference on Virology, August 20-23, 2012, Las Vegas, Nevada, USA
Chair, Organizing Committee
International Conference and Exhibition on Virology, September 5-7, 2011, Baltimore, Maryland, USA. Keynote address: “HIV-1 and Mononuclear Phagocytes: Omics Approaches to Understand Their Coexistence”
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.
Our effort is to use a proteomics and system biology approach supported by bioinformatics analyses to understand molecular mechanisms of pathological processes and apply this information to designing new strategies for disease prevention, early diagnosis, and control. Our primary model is the macrophage, which is a major component of the innate immunity system, and we are using state-of-the-art techniques in proteomics to investigate the following:
- Response of macrophage to HIV-1 infection;
- Response of macrophage to changes in cell's environment such as tissue injury; infection, toxicity of drugs used for treatment, and effect of drugs of abuse;
- Epigenetic regulation of macrophage responses; and
- Identification of proteomic biomarkers for the early detection and monitoring neurological complications associated with HIV-1 infection.
There are three ongoing projects in Proteomics Laboratory.
Project 1 is focused on changes in post-translational modifications of histones as a mechanism of regulating macrophage responses to insults and/or stimulatory molecules.
Project 2 is to use systems biology (holistic) experimental approaches to understand how HIV-1 is affecting macrophages to turn into machinery for productive infection allowing virus to persist in cells despite the macrophage's immune responses. Subsequently, we want to apply this information in designing new strategies for disease prevention, early diagnosis, and control. Using proteomic experiments, we will investigate mechanism(s) of how HIV-1 can bypass anti-viral intracellular immune surveillance. We are strongly interested in the effect of drugs of abuse on the function of the innate immunity system. Use of illicit drugs is an increasing social and health problem and has been documented to not only affect the brain but also the immune system making these individuals more susceptible to infections and other pathological effects. We also study the effect that anti-retroviral therapy may have on the function of macrophages.
Project 3 is to develop tools for bioinformatics analysis of proteomic data
Project 4 is focused on macrophages and microglia and their production of neurotoxic products that follow viral-infection and immune activation, which incite neuronal damage leading to HIV-1-neurocognitive disorders (HAND). This project is mostly focused on biomarker discovery using global proteomics profiling.
- Embury CM, Dyavarshetty B, Lu Y, Wiederin JL, Ciborowski P, Gendelman HE, Kiyota T. Cathepsin B Improves ß-Amyloidosis and Learning and Memory in Models of Alzheimer's Disease. J Neuroimmune Pharmacol. 2017 Jun;12(2):340-352. PMID: 27966067
- Ricaurte M, Schizas NV, Ciborowski P, Boukli NM. Proteomic analysis of bleached and unbleached Acropora palmata, a threatened coral species of the Caribbean. Mar Pollut Bull. 2016 Jun 15;107(1):224-32. PMID: 27105725
- Burns A, Ciborowski P. (2016) Acute exposure to methamphetamine alters TLR9-mediated cytokine expression in human macrophage. Immunobiology. 2016 Feb;221(2):199-207. PMID 26387832
- Araínga M, Guo D, Wiederin J, Ciborowski P, McMillan J, Gendelman HE. Opposing regulation of endolysosomal pathways by long-acting nanoformulated antiretroviral therapy and HIV-1 in human macrophages. Retrovirology. 2015 Jan 22;12:5. PMID: 25608975
- Wooden J, Ciborowski P. (2014) Chromatin Immunoprecipitation for Human Monocyte Derived Macrophages. Methods. S1046-2023(14)00285-0. PMID 25220915
- Haverland NA, Fox HS, Ciborowski P. (2014) Quantitative proteomics by SWATH-MS reveals altered expression of nucleic acid binding and regulatory proteins in HIV-1-infected macrophages. J Proteome Res. 13(4):2109-19. PMID: 24564501
- Wiederin J, Donahoe R, Anderson J, Yu F, Fox H, Ciborowski P* and Gendelman HE. (2012) Changes in the Plasma Proteome Follows Chronic Opiate Administration In Simian Immunodeficiency Virus Infected Rhesus Macaques. Drug and Alcohol Dependence 120:105-12, *- corresponding author. PMID 21821369
- Pottiez G and Ciborowski P. (2012) Elucidating gelsolin interacting domains using chemical cross-linking and MALDI-TOF/TOF mass spectrometry. Analytical Biochemistry 421:712-8. PMID 22226790
- Pottiez G, Jagadish G, Yu G, Letendre S, Ellis R, Duarte NA, Grant I, Gendelman HE, Fox HS and Ciborowski P. (2012) Plasma Proteomic Profiling in HIV-1 Infected Methamphetamine Abusers. PLoS One 7:e31031. PMID 22359561
- Jagadish T, Pottiez G, Fox H and Ciborowski P. (2012) Plasma gelsolin accumulates in macrophage nodules in brains of Simian Immunodeficiency Virus infected rhesus macaques. J Neurovirol. 2:113-9. PMID 22403026
- Pottiez G, Wiederin JL, Fox H, Ciborowski P. (2012) Comparison of 4-plex to 8-plex iTRAQ; quantitative measurements of proteins in human plasma samples. J Proteome Res. 11:3774-81. PMID 22594965
- Kraft-Terry SD, Engebretsen IL, Bastola DK, Fox HS, Ciborowski P, and Gendelman HE. (2011) Pulsed stable isotope labeling of amino acids in cell culture demonstrate dynamic interactions between HIV-1 and the monocyte-derived macrophage. J. Proteome Res. 3:2852-2862. PMID 21500866
- Wiederin J, Donahoe R, Anderson J, Yu F, Fox H, Gendelman HE, and Ciborowski P. (2010) Plasma proteomic analysis of simian immunodeficiency virus infection of rhesus macaques.. J. Proteome Res. 9:4721-4731. PMID 20677826
- Haverland N, Pottiez G, Wiederin J, and Ciborowski P. (2010) Immunoreactivity of anti-gelsolin antibody: Implications for biomarker validation. Journal of Translational Medicine 8:137. PMID 21171974
- Pottiez G, Haverland N and Ciborowski P. (2010) Mass spectrometric characterization of gelsolin isoforms. Rapid Communications in Mass Spectrometry, 24:2620-2624. PMID 20740538
- Silberring J and Ciborowski P. (2010) Biomarker discovery and clinical proteomics. Trends Analyt Chem. 29(2):128-140. PMID 20174458
- Haverland N, Fox H and Ciborowski P. Quantitative proteomics by SWATH-MS reveals altered expression of nucleic acid binding and regulatory proteins in HIV-1-infected macrophages. J Proteome Res. 2014, 13:2409 - 19. PMID 24564501