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 Chapters (5 out of 17 in print, 1)

• M. Goli, A. Yu, B. Gwan Cho, S. Gautam, J. Wang, C. D. Gutierrez-Reyes, P. Jiang, W. Peng, Y. Mechref “Chapter 8: 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, 391-441.
• 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 Spectrometry of Glycoproteins: Methods and Protocols, Methods in Molecular Biology book series, published by Humana Press, USA, 2271 (2021) 281-301.
• 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, 1598 (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.
• L. Veillon, S. Zhou, Y. Mechref "Chapter 22: Quantitative Glycomics: a combined analytical and bioinformatics approach" in A. Shukla (ed.) Proteomics in Biology Methods in Enzymology, published by Elsevier, USA, 585 (2017) 431-477.

Review Articles (8 out of 39)

• W. Peng, F. Kobeissy, S. Mondello, C. Barsa, Y. Mechref “MS-Based Glycomics: An Analytical Tool to Assess Nervous System Diseases,” Front. Neurosci., in press, https://doi.org/10.3389/fnins.2022.1000179.
• Y. Mechref, W. Peng, S. Gautam, P. Ahmadi, Y. Lin, J. Zhu, J. Zhang, S. Liu, A. G. Singal, Neehar D. Parikh, and D. M. Lubman "Mass Spec Based Biomarkers for early detection of HCC Using a Glycoproteomic Approach," Adv. Cancer Res.,https://doi.org/10.1016/bs.acr.2022.07.005, in press.
• W. Peng, C. D. Gutierrez Reyes, S. Gautam, A. Yu, B. G. Cho, M. Goli, K. Donohoo, F. Kobeissy, Y. Mechref "MS-Based Glycomics and Glycoproteomics Methods Enabling Isomeric Characterization," Mass Spectrom Rev., (2022) 1-40. https:doi.org/10.1002/mas.21713
• H. Jourdi, Z. Haj Hassan, O. Ashekyan, M. Fardoun, Z. Wehbe, D. Maaliki, M. Wehbe, S. Mondello, S. Abdelhady, S. Shahjouei, M. Bizri, Y Mechref, M. S Gold, K. K Wang, G, Dbaibo, H. Zaraket, A. H. Eid, F. Kobeissy "Neurological and Neuropsychological Changes Associated with SARS-CoV-2 Infection: New Observations, New Mechanisms" Neuroscientist, (2022) 1-20 DOI: 10.1177/1073858420984106.
• F. Kobeissy, A. Kobaisi, W. Peng, C. Barsa, M. Goli, A. Sibahi, S. El Hayek, S. Abdelhady, M. A. Haidar, M. Sabra, M. Orešič, G. Logroscino, St. Mondello, A. Eid, Y. Mechref, "Glycomics and Glycoproteomics in Neurodegenerative Disorders and Neurotrauma: Towards Personalized Markers," Cells, 11 (2022) 581.
• C. D. Gutierrez Reyes, P. Jiang, M. Atashi, A. Bennett, A. Yu, W. Peng, J. Zhong, and Y. Mechref "Advances in Mass Spectrometry-Based Glycoproteomics – An Update Covering the Period 2017-2021," Electrophoresis, 43 (2022) 370-387, https://doi.org/10.1002/elps.202100188.
• K. B. Donohoo, W. Peng, M. Goli, A. Yu, J. Wang, M. A. Hakim and Y. Mechref “Advances in Mass Spectrometry-Based Glycomics – An Update Covering the Period 2017-2021,” Electrophoresis, 43 (2022) 119-142, https://doi.org/10.1002/elps.202100199.
• C. D. Gutierrez Reyes, P. Jiang, M. Atashi, A. Bennett, A. Yu, W. Peng, J. Zhong, and Y. Mechref "Glycomics & Glycoproteomics: Approaches to Address Isomeric Separation of Glycans and Glycopeptides" J. Sep Sci, 44 (2021) 403-425.

Research Papers (36 out of 225)

• A. Yu, J. Zhao, W. Peng, S. P. S. Yadav, B. A. Molitoris, M. C. Wagner, and Y. Mechref, "Proteome Profiling of Kidney Brush-Border Membrane from Rat Models with Chronic Kidney Diseases," Proteomics Clin. Appl., in press, https://doi.org/10.1002/prca.202200063.
• C. D Gutierrez-Reyes, Md Abdul Hakim, M. Atashi, M. Goli, S. Gautam, J. Wang, A. I. Bennett, J. Zhu, D. M. Lubman, Y. Mechref, "LC-MS/MS Isomeric Profiling of N-Glycans derived from Low-Abundant Serum Glycoproteins in Mild Cognitive Impairment Patients," Biomolecules, 12 (2022) 1657, https://doi.org/10.3390/biom12111657.
• B. G. Cho, A. Banazadeh, M. Goli, S. Gautam, Y. Mechref, "Targeted Glycan Analysis with Parallel Reaction Monitoring (PRM) Using Quadrupole-Orbitrap Hybrid Mass Spectrometer," Anal. Chem., 94 (2022) 15215-15222, Supplementary Journal Cover Published.
• M. M. Cetin, W. Peng, D. Unruh, M. F. Mayer, Y. Mechref and K. Yelekci, "Design, Synthesis, Molecular Modeling and Bioactivity Evaluation of 1,10-Phenanthroline and Prodigiosin (Ps) Derivatives and Their Copper(I) Complexes against mTOR and HDAC Enzymes as Highly Potent and Effective New Anticancer Therapeutic Drugs" Front. Pharmacol. 13 (2022) 980479, https://doi.org/10.3389/fphar.2022.980479.
• J Zhong, Y. Huang, P. Jiang, Y. Mechref "Derivatization of Sialylated Glycopeptides Plus (DOSG+) Based Sialoglycopeptides Enrichment Using Cation Exchange Media," Anal. Chim. Acta., 1233 (2022) 340492. https://doi.org/10.1016/j.aca.2022.340492.
• J. Wang, W. Peng, A. Yu, M. Fokar and Y. Mechref “Comparative Transcriptomics and Proteomics of Cancer Cell Lines Cultivated by Physiological and Commercial Media,” Biomolecules, 12 (2022) 1575. https://doi.org/10.3390/biom12111575.
• J. Singh, S. Chakraborty, S. Kakkar, A. Yu, J. Zhao, Y. Mechref, S. Pratap, S. Yadav, B. Molitoris and M. C Wagner “Glycosylation of a key cubilin Asn residue results in reduced binding to albumin,” J Biol. Chem., 298 (2022) 102371, https://doi.org/10.1016/j.jbc.2022.102371.
• S. Gautam, S. Hiemstra, M. Goli, Y. Mechref “Development of an In-Source Peltier Heater for Pulled Capillary Nanospray Emitter Columns,” J. Am. Soc. Mass Spectrom., 33 (2022) 1799-1802 doi.10.1021/jasms.2c00167.
• R. Zhang, W. Peng, Y. Huang, S. Gautam, J. Wang, Y. Mechref and Haixu Tang, “A Reciprocal Best-hit Approach to Characterize Isomeric N-Glycans Using Tandem Mass Spectrometry,” Anal. Chem., 94 (2022) 10003-10010, doi.org/10.1021/acs.analchem.2c00229.
• P. Mandelare-Ruiz, M. McCauley, W. Peng, B. G. Cho, J. Wang, Y. Mechref, S. Loesgen, V. Weis “Heat stress alters the algal cell surface glycome and hinders the establishment of cnidarian-algal symbiosis,” Microbiol. Spectr., 10 (2022) e01567-22, https://doi.org/10.1128/spectrum.01567-22.
• S. Mondello, V. Sandner, M. Goli, E. Czeiter, K. Amrein, P. M. Kochanek, S. Gautam, B. G. Cho, R. Morgan, A. Nehme, G. Fiumara, A. Eid, Ch. Barsa, M. A. Haidar, A. Buki, F. H Kobeissy, and Y. Mechref, “Exploring Serum Glycome Patterns after Moderate to Severe Traumatic Brain Injury: A Prospective Pilot Study,” eClinicalMedicine, 50 (2022) 101494.
• J. Wang, W. Peng, A. Yu, M. Fokar and Y. Mechref, “Glycome Profiling of Cancer Cell Lines Cultivated in Physiological and Commercial Media,” Biomolecules, 12 (2022) 743; https://doi.org/10.3390/biom12060743.
• J. R Devlin, W. Santus, J. Mendez, W. Peng, A. Yu, J. Wang, X. Alejandro-Navarreto, K. Kiernan, M. Singh, P. Jiang, Y. Mechref, “Salmonella Enterica Serovar Typhimurium Chitinases Modulate the Intestinal Glycome and Promote Small Intestinal Invasion”, PLOS Pathogens, 18 (2022) e1010167, https://doi.org/10.1371/journal.ppat.1010167.
• J. Wang, X. Dong, A. Yu, Y. Huang, W. Peng and Y. Mechref, “Isomeric Separation of Permethylated Glycans by Long Reversed-Phase Liquid Chromatography (RPLC)-MS/MS,” Analyst, 147 (2022) 2048-2059, https://doi.org/10.1039/D2AN00010E, Inside cover page.
• M. Ali Haidar, Z. Shakkour, C. Barsa, M. Tabet, S. Mekhjian, H. Darwish, M. Goli, D. Shear, Jignesh D Pandaya, Y. Mechref, R. El Khoury, K. Wang, F. Kobeissy, “Mitoquinone Helps Combatting the Neurological, Cognitive, and Molecular Consequences of Open Head Traumatic Brain Injury at Chronic Time-point,” Biomedicines, 10 (2022) 250. https://doi.org/10.3390/biomedicines10020250.
• M Tabet; M El-Kurdi; M. A. Haidar; L. Nasrallah; M. A. Reslan; D. Shear; M. Sabra; S. Mondello; Y. Mechref; A. Shaito; R. El-Khoury; K. K. Wang; F. Kobeissy, “Mitoquinone Supplementation Alleviates Oxidative Stress and Pathologic Outcomes Following Repetitive Mild Traumatic Brain Injury at a Chronic Time Point,” Exp. Neurol., 351 (2022), 113987. https://doi.org/10.1016/j.expneurol.113987.
• S. Jayaraman, J. Kocot, S. H. Esfahani, N. J. Wangler, A. Uyar, Y. Mechref, P. C. Trippier, T. J. Abbruscato, A. Dickson, H. Aihara, D. A. Ostrov, V. T. Karamyan “Identification and characterization of two structurally related dipeptides that enhance catalytic efficiency of neurolysin,” J. Pharmacol. Exp. Ther., 379 (2021) 191-202. DOI: https://doi.org/10.1124/jpet.121.000840.
• R. Kawahara, K. Alagesan, M. Bern, W. Cao, R. J. Chalkley, K. Cheng, M. S. Choo, N. Edwards, R. Goldman, M. Hoffmann, Y. Hu, Y. Huang, J. Y. Kim, D. Kletter, B. Liquet-Weiland, M. Liu, Y. Mechref, B. Meng, S. Neelamegham, T. Nguyen-Khuong, J. Nilsson, A. Pap, G. W. Park, B. L. Parker, C. L. Pegg, J. M. Penninger, T. K. Phung, M. Pioch, E. Rapp, E. Sakalli, M. Sanda, B. L. Shulz, N. E. Scott, G. Sofronov, J. Stadlmann, S. Y. Vakhrushev, C. M. Woo, H.-Y. Wu, P. Yang, W. Ying, H. Zhang, Y. Zhang, J. Zhao, J. Zaia, S. M. Haslam, G. Palmisano, J. S. Yoo, G. Larson, K-H. Khoo, K. F. Medzihradszky, D. Kolarich, N. H. Packer, M. Thaysen-Andersen, “Community Evaluation of Glycoproteomics Informatics Solutions Reveals High-Performance Search Strategies of Glycopeptide Data,” Nat. Methods, 18 (2021) 1304-1316.
• A. Yu, J. Zhao, S. P. S. Yadav., B. A. Molitoris., M. C. Wagner, and Y. Mechref, “Changes in the Expression of Renal Brush Border Membrane N-Glycome in Model Rats with Chronic Kidney Diseases” Biomolecules, 11 (2021) 1677. https://doi.org/10.3390/biom11111677.
• A. Yu, J. Zhao, J. Zhong, J. Wang, S. P. S. Yadav., B. A. Molitoris., M. C. Wagner, and Y. Mechref, “Altered O-Glycomes of Renal Brush-border Membrane in Model Rats with Chronic Kidney Diseases” Biomolecules, 11(11) (2021) 1560; https://doi.org/10.3390/biom11111560.
• J. Zhao, E. Song, Y. Huang and Y. Mechref “Variability in the Glycosylation Patterns of gp120 Proteins from Different Human Immunodeficiency Virus Type 1 Isolates Expressed in Different Host Cells,” J. Proteome Res., 20 (2021) 4862-4874.
• B. G. Cho, S Gautam, W. Peng, Y. Huang, M. Goli, Y. Mechref “Direct comparison of N-glycans and their isomers derived from spike glycoprotein 1 of MERS-CoV, SARS-CoV-1 and SARS-CoV-2,” J. Proteome Res., 20 (2021) 4357-4365. Supplementary Journal Cover Published.
• C. D. Gutierrez Reyes, Y Huang, Mojgan Atashi, J. Zhang, J. Zhu, S. Liu, N D. Parikh, A. G. Singal, J. Dai, D. M. Lubman and Y. Mechref, “Parallel reaction monitoring – mass spectrometry (PRM-MS) quantitative analysis of isomeric N-glycopeptides derived from human serum haptoglobin of patients with cirrhosis and hepatocellular carcinoma” Metabolites, 11 (2021) 563.
• B. G. Cho, P. Jiang, M. Goli, S. Gautam, Y. Mechref "Using Micro Pillar Array Columns (µPAC) for the Analysis of Permethylated Glycans," Analyst, 146 (2021) 4374-4383. https://doi.org/10.1039/D1AN00643F.
• S Gautam, Y Geldiyev, A Ibrabuimov, Y. Mechref, JL Padgett, W Peng, "Object classification in analytical chemistry via data-driven discovery of partial differential equations" Comp and Math Methods., 3 (2021) e1164, doi: 10.1002/cmm4.1164.
• S. Mondello, F. Kobeissy, Y. Mechref, J. Zhao, S. El-Hayek, K. Zibara, E. Antelmi, M. Moresco, G. Plazzi, F. I. I. Cosentino, R. Ferri, "Searching for Novel Candidate Biomarkers of RLS in Blood by Proteomic Analysis," Nat. Sci. Sleep, 13 (2021) 873-883.
• R. Zhang, W. Peng, S. Gautam, Y. Huang, Y. Mechref, H. Tang "GlycanGUI: Automated Glycan Annotation and Quantification Using Glucose Unit Index (GUI)," Front. Chem., 9:707382, https://doi.org/10.3389/fchem.2021.707382.
• R. Zhang, J. Zhu, D. Lubman, Y. Mechref, H. Tang, "GlycoHybridSeq: Automated Identification of N-linked Glycopeptides Using Electron Transfer/High-energy Collision Dissociation (EThcD)," J. Proteome Res., 20 (2021) 3345-3352.
• Y. Zu, L. Zhao, L. Hao, Y. Mechref, M. Zabet-Moghaddam, P. Keyel, M. Abbasi, D. Wu, J. Dawson, R. Zhang, S. Nie, N. Moustaid-Moussa, M. Kolonin, A. Daquinag, L. Brandi, I. Warraich, S. San Francisco, X. Sun, Z. Fan, S. Wang "Browning white adipose tissue using adipose stromal cell-targeted resveratrol-loaded nanoparticles for combating obesity," J. Control. Release., 333 (2021) 339-351, https://doi.org/10.1016/j.jconrel.2021.03.022.
• J. Zhong, Y. Huang, Y. Mechref "Derivatization of Sialylated Glycopeptides (DOSG) Enabling Site-Specific Isomeric Profiling using LC-MS/MS," Anal. Chem., 93 (2021) 5763-5772.
• S. Gautam, A. Banazadeh, B. G. Cho, M. Goli, J. Zhong, Y. Mechref "Mesoporous Graphitized Carbon (MGC) Column for Efficient Isomeric Separation of Permethylated Glycans", Anal. Chem., 93 (2021) 5061–5070.
• B. G. Cho, C. D. Gutierrez-Reyes, Y. Mechref "N-glycomics of Cerebrospinal Fluid: Method Comparison," Molecules, 26 (2021) 1712.
• H. Dakik, S. Mantash, A. Nehme, F. Kobeissy, M. Zabet-Moghaddam, P. Mirzaei, Y. Mechref, A. Gaillard, L. Prestoz, K. Zibara, "Analysis of the neuro-proteome associated with cell therapy in a mouse model of Parkinson's disease," Front. Neurosci., 15 (2021) 621121 https://doi.org/10.3389/fnins.2021.621121.
• S. P. Yadav, R. Sandoval, J. Zhao, Y. Huang, E. Wang, S. Kumar, S. Campos-Bilderback, G. Rhodes, Y. Mechref, B. Molitoris, and M. Wagner "Mechanism of How Carbamylation Reduces Albumin Binding to FcRn contributing to increased vascular clearance." Am J Physiol-Renal, 320 (2021) F114-F129, https://doi.org/10.1152/ajprenal.00428.2020.
• R. Dhakal, R. Nieman, D. C. A. Valente, T. M. Cardozo, B. Jayee, A. Aqdas, W. Peng, A. A. J. Aquino, Y. Mechref, H. Lischka, H. Mouss, "A General New Method for Calculating the Nonpolar Surface of a Molecule and Applications", Inter. J. Mass Spectrom., 461 (2021) 116495, https://doi.org/10.1016/j.ijms.2020.116495.
• J. Zhao, W. Peng, X. Dong, Y. Mechref "Characterization of the Glycosylation of NIST Monoclonal Antibody Reference Material by LC-MS/MS-Based Glycoproteomics Approach," J. Proteom. Res., 20 (2021) 818-830.