Dr. Yehia Mechref

Principal Research Interests

• Analytical
• Bioanalytical
• Chemical Separation
• Glycomics
• Glycoproeomics/Proteomics

The current advances in bioanalytical methods and instrumentation have greatly facilitated the understanding of biological processes at the molecular level. Every living organism in its environment represents a biochemically unique system whose biological functions can be better understood through analytical measurements. Isolated analytical measurements, which may help assessing the state of health within the organisms under study, are now routinely being made. Distinguishing between the “apparently healthy” and “diseased” individuals in clinical chemistry assays is often complicated by the biochemical individuality which has been recognized as an experimental complication of acquiring data from human subjects. Moreover, this aspect commonly results in considerable ranges for both often exist.

The rapidly developing fields of genomics, transcriptomics, proteomics, glycomics, and metabolomics are generating a vast body of biochemical information which is only sorted out through Systems Biology. Systems Biology, here, is referring to the strategy of pursuing integration of complex data about the interactions in biological systems from diverse bioanalytical techniques using multidisciplinary tools and personnel. Many research laboratories have been focusing their efforts on the overwhelming task of characterizing proteins and their voluminous posttranslation modifications following the Human Genome Project and the subsequent efforts to characterize the genomes of model animals. Inquiries into the glycomes and metabolomes of physiological fluids and tissues have been prompted by the unprecedented advances in biomolecular characterization and quantification of proteins. The abality to address these inquiries have been mainly attributed to the methodological/technological advances in biomolecular mass spectrometry and microscale separation science, as well as to the greatly improved computational capabilities (bioinformatics) which is facilitating fast data visualization and interpretation. The overarching activities in my research group are focused on the utility of molecular mass spectrometry to understand biomolecular changes attributing to disease development and progression.

Glycomics and glycoproteomics continue to be highly dynamic and interesting research areas due to the needs to comprehensively understand the biological attributes of glycosylation in many important biological functions such as immune response, cell development, cellular differentiation/adhesion and host-pathogen interactions. Moreover, aberrant glycosylation for decades has been recognized as the attribute of many mammalian diseases, including osteoarthritis, cystic fibrosis and cancer. This being said, glycomic and glycoproteomic analyses remain to be analytically very challenging mainly due to the high complexity and microheterogeneity of glycosylation processes and machineries. Therefore, more cutting-edge-analytical approaches are needed to allow more comprehensive characterization of glycosylation and subsequently better understanding of its biological roles. The ultimate goal of the research activities of my group is the comprehensive characterization of glycoprotein glycosylation sites and microheterogeneity of such sites. Accordingly, we are developing several glycomic and glycoproteomic approaches facilitating the achievement of this ultimate goal. Since interpretation and processing of glycomic and glycoproteomic data is laborious and time consuming, we are also collaborating with bioinformatics experts to develop different bioinformatic tools aiding rapid and automated data interpretation and processing. These research activities are intended to facilitate the analysis of large numbers of biological samples, thus facilitating a better understanding of disease development and progression at a molecular level.

Representative Publications

Book Chapter (4 out of 14)

• K.M. Wooding, R. Zhu, L. Zacharias Y. Mechref "Glycoprotein enrichment analytical techniques: advantages and disadvantages" in A. Shukla (ed.) Proteomics in Biology Methods in Enzymology, published by Elsevier, USA, 2017. in press.
• L. Veillon, S. Zhou, Y. Mechref "Quantitative Glycomics: a combined analytical and bioinformatics approach" " in A. Shukla (ed.) Proteomics in Biology Methods in Enzymology, published by Elsevier, USA, 2017. in press.
• S. Zhou, K. M. Wooding, Y. Mechref "Analysis of Permethylated Glycan by Liquid Chromatography (LC) and Mass Spectrometry (MS)" in M. Wuhrer and G. Lauc (eds.), High-throughput glycomics and glycoproteomics, Methods in Molecular Biology book series, published by Humana Press, USA, 2016. in press.
• R. Zhu, E. Song, A. Hussein, F. Kobeissy, Y. Mechref "Glycoproteins Enrichment and LC-MS/MS Glycoproteomics in Central Nervous System Applications" in S. Stevens and F. Kobeissy (eds.), Neuroproteomics, Methods in Molecular Biology book series, published by Humana Press, USA, 2016. in press.

Review Articles (10 out of 22)

• A. Banazadeh, L. Veillon, M. Zabet, Y. Mechref, "Recent Advances in Mass Spectrometric Analysis of Glycoproteins", Electrophoresis, (2017), in press.
• A. Nokkari, Y. Mechref, S. Mondello, M. S. Kindy, A. Jaffa, F. Kobeissy, "Implication of the Kallikrein-Kinin System on Neurological Disorders: Quest for Potential Biomarkers and Mechanisms", Prog. Neurobiol., (2017), in press.
• H. Abou Abbass, H. Abou El Hassan, H. Bahmad, A. Zebian, R. Youssef, J. Ismail, K. Zibara, R. Zhu, H. Darwish, Y. Mechref, F. Kobeissy, Electrophoresis, 11 (2016) 1549-1561.
• K. M. Wooding and Y. Mechref, "Characterization of Pharmaceutical IgG and Biosimilars Using Miniaturized Platform and LC-MS/MS", Curr. Pharm. Biotechnol., 17 (2016) 788 - 801.
• E. Song and Y. Mechref "Defining Glycoprotein Cancer Biomarkers by Mass Spectrometry" Biomark. Med., 9 (2015) 835-844.
• Y. Mechref, C. Lebrilla "30th ASMS Asilomar Conference on Advances in Glycomics and Glycoproteomics: Methods and Applications" J. Amer. Soci. Mass Spectrom. 26 (2015) 1047-1050.
• F. Kobeissya,T. H. Mouhieddine, A. Nokkari, M. Itani, M. Mouhieddine, Z. Zhang, R. Zhu, M. S. Gold, K. K.Wang, Y. Mechref "Recent updates on drug abuse analyzed by neuroproteomics studies: Cocaine, Methamphetamine and MDMA" Transl. Proteomics, 3 (2014) 38-52.
• Y. Mechref, Y. Hu, S. Zhou, and H. Tang, "Quantitative Glycomics by Mass Spectrometry and Liquid Chromatography-Mass Spectrometry." Encyclopedia of Analytical Chemistry. (2014)1–22.
• H. Tang, A. Mayampurath, C. Yu and Y Mechref "Bioinformatics Protocols in Glycomics and Glycoproteomics" Current Protocols in Protein Science, 76:2.15 (2014) 1-7.
• Y. Mechref, Y. Hu, J. L. Desantos-Garcia, and H. Tang, "Quantitative Glycomic Strategies" Mol. Cell. Proteomics, 12 (2013) 874-884.

Research Papers (32 out of 153)

• L. G. Zacharias, A. K. Hartmann, E. Song, J. Zhao, R. Zhu, P. Mirzaei, and Y. Mechref "HILIC and ERLIC Enrichment of Glycopeptides Derived from Breast and Brain Cancer Cells" J. Proteome Res., (2016), in press.
• H. Yin, J. Zhu, J. Wu, Z. Tan, M. An, S. Zhou, Y. Mechref, D. M. Lubman, "A procedure for the analysis of site-specific and structure-specific fucosylation in Alpha-1-Antitrypsin", Electrophoresis, (2016), in press.
• W. A. Elmasri, T. Yang, M-E. F. Hegazya, Y. Mechref, P. W. Pare "Iridoid and secoiridoid glycosides permethylation enhances chromatographic separation and chemical ionization for LC-MS/MS structural characterization", Rapid Commun. Mass Spectrom., 30 (2016) 2033-2042.
• S. Jayaraman, R. Zhu, N. J. Wangler, Y. Mechref, T. J. Abbruscato, D. A. Ostrov, and V. T. Karamyan, "Discovery of Small molecule Allosteric Potentiotiators of Peptidase Neurlysin," J. Biotech., 234 (2016) 105-115.
• S. Zhou, Y. Hu, S. I. Snovida, J. C. Rogers, J. Saba and Y. Mechref "Quantitative LC-MS/MS Glycomic Analysis of Biological Samples Using AminoxyTMT", Anal. Chem., 88 (2016) 7515-7522.
• H. Abou Abbass, H. Bahmad, H. Abou El Hassan, K. Mallah, J. Fares, A. Zebian, K. Zibara, E. Hemadeh, Y. Comair, S. Atweh, H. Darwish, R. Zhu, Y. Mechref, F. Kobeissy "Deciphering Glycomics and Neuroproteomic Alterations in Experimental TBI: Comparative Analysis to Aspirin & Clopidogrel Treatment", Electrophoresis, 11 (2016) 1562-1576.
• S. Zhou, Y. Hu, Y. Mechref "High-Temperature LC-MS/MS of Permethylated Glycans Derived from Glycoproteins", Electrophoresis, 11 (2016) 1506-1513.
• J. Zhao, E. Song, R. Zhu, Y. Mechref, "Parallel Data Acquisition of In-source Fragmented Glycopeptides to Characterize the Peptide Backbones and Glycan Structures", Electrophoresis, 11 (2016) 1420-1430.
• X. Dong, S. Zhou, N. Tello, and Y. Mechref, "LC-MS/MS Analysis of Permethylated Free Oligosaccharides and N-glycans Released from Human Milk", Electrophoresis, 11 (2016) 1532-1548.
• S. Zhou, N. Tello, A. Harvey, B. Boyes, R. Orlando and Y. Mechref, "Reliable Quantitative glycomics using LC-MS and iGlycoMab Stable Isotope Labeled Glycan Standard", Electrophoresis, 11 (2016) 1489-1497.
• Y. Hu, T. Shihab, and Y. Mechref "LC-MSMS of Permethylated N-glycans Derived from Model Glycoproteins and Human Blood Serum", Electrophoresis, 11 (2016) 1498-1505.
• C-Y. Yu, A. Mayampurath, E. Song, Y. Mechref, and Haixu Tang "Automated glycan sequencing from tandem mass spectra of N-linked glycopeptides" Anal. Chem., 88 (2016) 5725-5732. DOI: 10.1021/acs.analchem.5b04858.
• R. Zhu, F. Kobeissy, M. S. Gold, K. K. Wang, Y. Mechref "Effect of Chronic Methamphetamine Exposure on the Neuroproteomics of Rat Brain Tissues" PLOS One, PLoS ONE 11(4) (2016): e0151034. doi:10.1371/journal.pone.0151034.
• F. Niere, S. Namjoshi, E. Song, G.A. Dilly, G. Schoenhard, B.V. Zemelman, Y. Mechref, K. F. Raab-Graham "Analysis of proteins that rapidly change upon mTORC1 repression identifies Park7 as a novel protein aberrantly expressed in Tuberous Sclerosis Complex" Mol. Cell Proteomics, 15 (2016) 426-444.
• W. A. Elmasri, M-E. F. Hegazy, Y. Mechref, P. W. Pare "Structure-antioxidant and anti-tumor activity of Teucrium polium phytochemicals" Phytochem. Lett., 15 (2016) 81-87.
• Y. Zhang, C-Y. Yu, E Song, S. C. Li, Y. Mechref, H. Tang, and X. Liu "Identification of glycopeptides with multiple hydroxylysine O-glycosylation sites by tandem mass spectrometry" J. Proteome Res., 14(12) (2015) 5099-5108.
• N. C. Wildburger, S. Zhou, L. G. Zacharias, R. A. Kroes, J. R. Moskal, M. Schmidt, P. Mirzaei, J. Gumin, F. F. Lang, Y. Mechref, and C. L. Nilsson "Integrated Transcriptomic and Glycomic Profiling of Glioma Stem Cell Xenografts" J. Proteome Res., 14(9) (2015) 3932-9.
• A. Nokkari, T. H. Mouhieddine, M. M. Itani, W. Abou-Kheir, G. Daoud, R. Zhu, Y. Mechref, J. Soueid, M. Al Hariri, S. Mondello, A. A. Jaffa, F. Kobeissy "Characterization of the Kallikrein-Kinin System Post Chemical Neuronal Injury: An In Vitro Biochemical and Neuroproteomics Assessment" PLoS ONE 10(6) (2015) e0128601.
• E. Song, Y. Hu, A. Hussein, C-Y. Yu, H. Tang, Y. Mechref "Comprehensive Characterization of the Glycosylation Site of Human PSA Prompted by Missense Mutation using LC-MS/MS" J. Proteome Res., 14 (2015) 2872-83.
• T.-H. Tsai, E. Song, R. Zhu, C. Di Poto, M. Wang, Y. Luo, R. Varghese, M. Tadesse, D. Ziada, C. Desai, K. Shetty, Y. Mechref, H. Ressom, "LC-MS/MS based serum proteomics for identification of candidate biomarkers for hepatocellular carcinoma" Proteomics, 15 (2015) 2369-2381.
• *Y Hu, A. Mayampurath, S. Khan, J K. Cohen, Y. Mechref and S. L. Volchenboum, "N-linked glycan profiling in neuroblastoma cell lines" J. Proteome Res., 14 (2015) 2074-2081.
• W. A. Elmasri, M-E. F. Hegazy, Y. Mechref and P. W. Pare´, "Cytotoxic saponin poliusaposide from Teucrium polium" RSC Adv., 5 (2015) 27126–27133.
• S. Zhou, Y. Hu, J. L. DeSantos-Garcia and Y. Mechref "Reliable Quantification of Permethylated N-Glycans through Multiple Reaction Monitoring (MRM) LC-MSMS" J. Amer. Soci. Mass Spectrom. 26 (2015) 596-603.
• W. A. Elmasri, T. Yang, P. Tran, M-E. F. Hegazy, A. N. Hamood, Y. Mechref, Paul W. Paré "Teucrium polium phenylethanol and iridoid glucoside identification and inhibition of biofilm forming Staphylococcus aureus" J. Natur. Products, 78 (2015) 2-9.
• Y. Hu, S. Zhou, C-Y. Yu, H. Tang and Y. Mechref "Automated Annotation and Quantitation of Glycan by LC-ESI-MS analysis using MultiGlycan-ESI Computational Tool" Rapid Commun. Mass Spectrom., 29 (2015) 1-8.
• E. Song, A. Mayampurath, C-Y. Yu, H. Tang, and Y. Mechref "Glycoproteomics: Identifying the Glycosylation of Prostate Specific Antigen at Normal and High Isoelectric Point by LC-MS/MS." J. Proteome Research, 13 (2014) 5570-5580.
• E. Song, R. Zhu, Z. T. Hammoud, Y. Mechref "LC-MS/MS Quantitation of Esophagus Disease Blood Serum Glycoproteins by Enrichment with Hydrazide Chemistry and Lectin Affinity Chromatography." J. Proteome Research, 13 (2014) 4808-4820.
•  T.H. Tsai, M. Wang, C. Di Poto, Y. Hu, S. Zhou, Y. Zhao, R.S. Varghese, Y. Luo, M.G. Tadesse, D.H. Ziada, C.S. Desai, K. Shetty, Y. Mechref, H.W. Ressom "LC-MS Profiling of N-glycans Derived from Human Serum Samples for Biomarker Discovery in Hepatocellular Carcinoma." J. Proteome Research, 13 (2014) 4859-4868.
•  A. Mayampurath, E. Song, A. Mathur, C.Y. Yu, Z. Hammoud, Y. Mechref, H. Tang "Label-Free Glycopeptide Quantification for Biomarker Discovery in Human Sera." J. Proteome Research, 13 (2014) 4821-4832.
•  A. I. Molosh, P. L. Johnson, J. P. Spence, D. Arendt, L. M. Federici, C. Bernabe, S. P. Janasik, Z. M. Segu, R. Khanna, C. Goswami, W. Zhu, S-J. Park, L. Li, Y. Mechref, D. W. Clapp, A. Shekhar "Social learning and amygdala disruptions in Nf1 mice are rescued by blocking p21-activated." Nature Neuroscience, 17 (2014) 1583-1590.
•  W.A. Elmasri, M.E. Hegazy, M. Aziz, Koksal E, W. Amor, Y. Mechref, A.N. Hamood, D.B. Cordes, P.W. Paré "Biofilm blocking sesquiterpenes from Teucrium polium." Phytochemistry, 103 (2014) 107-113.
•  A. Mayampurath, C.Y. Yu, E. Song, J. Balan, Y. Mechref, H. Tang "Computational framework for identification of intact glycopeptides in complex samples." Anal. Chem., 86(1) (2014) 453-463.