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 ability 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 16)

• M. Goli, A. Yu, B. Gwan Cho, S. Gautam, J. Wang, C. D. Gutierrez-Reyes, P. Jiang, W. Peng, Y. Mechref “LC-MS/MS in Glycomics and Glycoproteomics Analyses” in Z. El Rassi (Ed.) Carbohydrate Analysis by Modern Liquid Phase Separation Techniques, 2e. Published by Elsevier, USA, 2021.
• B. Gwan Cho, A. Banazadeh, W. Peng, J. Zhao, M. Goli, S. Gautam, A. Hussein, Y. Mechref “Determination of Isomeric Glycan Structures by Permethylation and Liquid Chromatography - Mass Spectrometry (LC-MS)” in A. Delolbel (ed.) Mass Specrometry of Glycoproteins: Methods and Protocols, Methods in Molecular Biology book series, published by Humana Press, USA, 2021.
• 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, 2017. 213-227.
• K.M. Wooding, R. Zhu, L. Zacharias, Y. Mechref “Chapter 21: Glycoprotein enrichment analytical techniques: advantages and disadvantages” in A. Shukla (ed.) Proteomics in Biology Methods in Enzymology, published by Elsevier, USA, 585 (2017) 397-429.

Review Articles (7 out of 29)

• Y Mechref, W. Peng, Y. Huang “Recent Advances in Isomeric N- and O-Glycomics” LC-GC: Current Trends in Mass Spectrometry, July 2019, 23-31.
• Y. Mechref, W. Peng, A. Banazadeh, Y. Huang, Y. Hu, S. Zhou, and H. Tang, “Quantitative Glycomics by Mass Spectrometry and Liquid Chromatography-Mass Spectrometry.” Encyclopedia of Analytical Chemistry. (2019) First published: 24 December 2018 https://doi.org/10.1002/9780470027318.a9400.pub2.
• A. Yu, J. Zhao, W. Peng, A. Banazadeh, S. D. Williamson, M. Goli, Y. Huang, Y. Mechref “Advances in Mass Spectrometry-based Glycoproteomics” Electrophoresis, 39 (2018) 3104-3122.
• X. Dong, Y. Huang, B. G. Cho, J. Zhong, S. Gautam, W. Peng, S. D. Williamson, A. Banazadeh, K. Y. Torres-Ulloa and Y. Mechref “Advances in Mass Spectrometry-Based Glycomics,” Electrophoresis, 39 (2018) 3063-3081.
• W. Peng, J. Zhao, X. Dong, A. Banazadeh, Y. Huang, A. Hussien, Y. Mechref “Clinical Application of Quantitative Glycomics,” Exp. Rev. Proteomics, 15 (2018) 1007-1031.
• 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., 165-167 (2018) 26-50.
• L. Veillon, C. Fakih, H. A. Hassan, F. Kobeissy, Y. Mechref “Glycosylation Changes in Brain Cancer”, ACS Chem. Neurosci., 9 (2018) 51-72.

Research Papers (23 out of 187)

• A. Fahs, F. Ramadan, F. Ghamloush, A. J Ayoub, F. A. Ahmad, F. H Kobeissy, Y. Mechref, J. Zhao, R. Zhu, N. Hussein, R. Saab, S. E. Ghayad "Effects of the oncoprotein PAX3-FOXO1 on modulation of exosomes function and protein content: Implications on oxidative stress protection and enhanced plasticity,” Front. Oncol., in press, doi: 10.3389/fonc.2020.01784.
• H. Bahmad, W. Peng, R. Zhu, F. Ballou, A. Monzer, M. Elajami, F. Kobeissy*,W. Abou-Kheir*, Y. Mechref* “Protein Expression Analysis of an In Vitro Murine Model of Prostate Cancer Progression: Towards Identification of High-Potential Therapeutic Targets,” J. Pers. Med., 10 (2020) 83.
• S. Gautam, W. Peng, B. G. Cho, Y. Huang, A. Banazadeh, A. Yu, X. Dong, Y. Mechref “Glucose Unit Index (GUI) of Permethylated Glycans for Effective Identification of Glycans and Glycan Isomers,” Analyst, https://doi.org/10.1039/D0AN00314J.
• X. Dong, S. Mondello, F. Kobeissy, F. Talih, R. Ferri, Y. Mechref “LC-MS/MS Glycomics of Idiopathic Rapid Eye Movement (REM) Patients with Restless Legs Syndrome (RLS)”, J. Proteome Res., 19 (2020) 2933–2941
• R. Zhu, Y. Huang, J. Zhao, J. Zhong and Y. Mechref “Isomeric Separation of Glycopeptides Derived from Glycoproteins by Porous Graphitic Carbon (PGC) LC-MS/MS,” Anal. Chem., 92 (2020) 9556-9565.
• R. Saoud, M. A. Jaffa, A. A. Habib, P. Khoueiry, J. Zhao, M. Al Hariri, R. Zhu, A. Hassan, F. N. Ziyadeh, F. Kobeissy, Y. Mechref and A. A. Jaffa “Proteomic Analysis of Bradykinin Signaling in Podocytes” J. Adv. Res., 24 (2020) 409-422.
• T. R. Tivey, J. E. Parkinson, P. E. Mandelare, D. A. Adpressa, W. Peng, X. Dong, Y. Mechref, V. M. Weis, S. Loesgen “N-linked surface glycan biosynthesis, composition, inhibition, and function in cnidarian-dinoflagellate symbiosis”, Microb. Ecol., 80 (2020) 223-236.
• S. Mondello, V. A. Guedes, C. Lai, E. Czeiter, K. Amrein, F. Kobeissy, Y. Mechref, A. Jeromin, S. Mithani, C. Martin, C. L. Wagner, A. Czigler, L. Tóth, B. Fazekas, A. Buki, and J. Gill “Circulating Brain Injury Exosomal Proteins following Moderate-to-Severe Traumatic Brain Injury: Temporal Profile, Outcome Prediction and Therapy Implications”, Cells, 9 (2020) 977. doi: 10.3390/cells9040977.
• P. Mirzaei, Wenjing Peng, R. Zhu, S. Zhou, Y. Mechref “Comparative Membrane N-Glycomics of Different Breast Cancer Cell Lines to Understand Breast Cancer Brain Metastasis,” J. Proteome Res., 19 (2020) 854-863.
• M. De Leoz et al. “NIST Interlaboratory Study on Glycosylation Analysis of Monoclonal Antibodies: Comparison of Results from Diverse Analytical Methods,” Mol. Cell. Proteomics, 19 (2020) 11-30.
• W. Peng, R. Zhu, S. Zhou, P. Mirzaei, and Y. Mechref “Integrated Transcriptomics, Proteomics, and Glycomics Reveals the Association between Up-regulation of Sialylated N-glycans/Integrin and Breast Cancer Brain Metastasis,” Sci. Rep., 9 (2019) 1-13.
• G. Rammal, A. Fahs, F. Kobeissy, Y. Mechref, Z. Jingfu, R. Zhu, M. Diab-Assaf, R. Saab, S. Ghayad, “Proteomic profiling of rhabdomyosarcoma-derived exosomes yield insights into their functional role in paracrine singling,” J. Proteome Res., 18 (2019) 3567-3579. DOI: 10.1021/acs.jproteome.9b00157
• B.G. Cho, L. Veillon, Y. Mechref “N-glycan profile of cerebrospinal fluids from Alzheimer's Disease patients using LC-MS” J. Proteom Res., 18 (2019) 3770-3779. DOI: 10.1021/acs.jproteome.9b00504
• W. Peng, M. Goli, P. Mirzaei, Y. Mechref “Revealing the Biological Attributes of N-Glycan Isomers in Breast Cancer Brain Metastasis Using Porous Graphitic Carbon (PGC) Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS),” J. Proteome Res., 18 (2019) 3731-3740. DOI: 10.1021/acs.jproteome.9b00429
• X. Dong, W. Peng, C.-Y. Yu,; S. Zhou,; K. Donohoo, H. Tang, Y. Mechref, “8-plex LC-MS/MS Analysis of Permethylated N-glycans Achieved by Using Stable Isotopic Iodomethane,” Anal. Chem., 91 (2019) 11794-11802. DOI: 10.1021/acs.analchem.9b02411
• A. Banazadeh, R. Nieman, M. Goli, W. Peng, A. Hussien, E. Bursal, H. Lischka, Y. Mechref “Characterization of Glycan Isomers Using Magnetic Carbon Nanoparticles as a MALDI co-Matrix,” RSC Advances, 9 (2019) 20137-20148.
• A. Nehme, F. Kobeissy, J. Zhao, R. Zhu, P. Feugier, Y. Mechref and K. Zibara “Functional Pathways Associated with Human Carotid Atheroma: A Proteomics Analysis,” Hypertens. Res., 42 (2019) 362-373.
• X. Dong, S. Mondello, F. Kobeissy, F. Talih, R. Ferri, and Y. Mechref “LC-MS/MS Glycomics of Idiopathic Rapid Eye Movement (REM) Sleep Behavior Disorder”, Electrophoresis, 39 (2018) 3096-3103.
• J. Zhong, A. Banazadeh, W. Peng, Y. Mechref “A Carbon Nanoparticles-based Solid-phase Purification Method Facilitating Sensitive MALDI-MS Analysis of Permethylated N-Glycans”, Electrophoresis, 39 (2018) 3087-3095.
• S. Mondello, F. Kobeissy, Y. Mechref, J. Zhao, S. El Hayek, FII. Cosentino, E. Antelmi, M. Moresco, G. Plazzi, R. Ferri “Novel Biomarker Signatures for Idiopathic REM Sleep Behavior Disorder: a Proteomic and System Biology Approach” Neurology, 91 (2018) e1710-e1715.
• A. Banazadeh, S. Williamson, M. Zabet., A. Hussien, Y. Mechref, “Magnetic Carbon Nanocomposites as A MALDI co-Matrix Enhancing MS-Based Glycomics” Anal. Bioanal. Chem., 410 (2018) 7395-7404.
• A. Banazadeh, W. Peng, L. Veillon, Y. Mechref “Carbon Nanoparticles and Graphene Nanosheets as MALDI Matrices in Glycomics: A New Approach to Improve Glycan Profiling in Biological Samples” J. Am. Soc. Mass Spectrom., 29 (2018) 1892-1900.
• R. Zhu, S. Zhou, W. Peng, Y. Huang, P. Mirzaei, K. Donohoo and Y. Mechref “Enhanced Quantitative LC-MS/MS Analysis of N-linked Glycans Derived from Glycoproteins Using Sodium Deoxycholate Detergent” J. Proteome Res., 17 (2018) 2668-2678.