RESEARCH

Applying mass spectrometry to characterize protein and RNA modifications and explore their biological roles.
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Comprehensive Characterization of Glycosylation Patterns Using Mass Spectrometry

Glycans modify proteins, lipids, and even RNA molecules to form the glycocalyx, a dense regulatory coat on cell surfaces that plays a crucial role in cellular functions. Changes in glycosylation patterns correlate closely with the development and further disease progression. Consequently, the profiling of glycans in biology and medicine is an important approach. This advance regarding glycan analysis, therefore, has been underpinned by mass spectrometry techniques. These allow high-throughput, sensitive, and precise characterization of both composition and structure.

In our lab, we focus on developing state-of-the-art mass spectrometry to enable quantitative structural identification of glycosylation on proteins and RNA molecules. This includes the development of comprehensive workflows, which are tightly integrating advanced sample preparation with data acquisition and computational analysis into unprecedented accuracy and depth in glycosylation profiling. It is in this backdrop that our efforts have gone toward providing an overarching system explaining how different glycan architectures influence molecular interactions, intracellular signaling, and pathogenic mechanisms and thereby link glycomics to functional biology.

Unraveling Glycan-Mediated Interaction Networks via Chemical Biology Approaches

Biological interaction networks play a central role in deciphering complicated molecular machinery and signal transduction pathways active in the cell, affecting development and disease course. Biomolecules are frequently modified, and such modifications determine their functions in various cellular contexts. Of those, glycosylation, which mediates the formation of the glycocalyx, presents several of the biggest challenges to inquiry. So far, the role that various glycan structures play in modulating membrane interaction networks has been only poorly explored, despite their widely recognized key role in cellular signaling and recognition.

In concert with this limitation, we have established expertise in a set of chemical biology toolbox, including proximity labeling, crosslinking mass spectrometry, and affinity purification mass spectrometry, which enable construct of the networks of glycan-mediated interactions at far superior levels of specificity and sensitivity. Using these sophisticated approaches, we aim to achieve a comprehensive molecular understanding of how glycosylation regulates major biological processes. The ultimate goal is to explain how glycosylation acts at the cellular level to change cellular functions and potentially uncover new therapeutic interventions in diseases caused by glycosylation dysregulation.

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研究图片
Quantitative Mass Spectrometry-Based Epitranscriptomics

RNA participates directly in events related to both gene expression and regulation in organisms. More than 150 different chemical modifications have been identified in RNA that participate in significant functions, including mRNA stability, RNA conformation, translation efficiency, and splicing. RNA modifications have been implicated in a variety of diseases, including cancers and neurological disorders, through their dysregulation, underlining their critical relevance to cellular physiology and disease mechanisms. Conventional genomic methods have various limitations in simultaneously characterizing and quantifying multiple RNA modifications, which makes mass spectrometry a unique tool for these tasks. Mass spectrometry enables direct identification of modified entities through their specific mass shifts and provides accurate quantitative information.

Our laboratory is highly motivated to advance mass spectrometry-based methodologies for the high-throughput and quantitative characterization of RNA modifications. Through the creation of novel mass spectrometry techniques, we intend to investigate the dynamics of RNA modifications across different disease conditions, thereby addressing significant gaps in the understanding of RNA biology. This research aspires to uncover the regulatory roles of RNA modifications in gene expression, providing valuable insights into epitranscriptomic processes and identifying prospective biomarkers and therapeutic targets.

Lab Members

Shining brilliantly like a galaxy of stars
Yixuan (Axe) Xie

Yixuan (Axe) Xie 谢一轩

(Principal Investigator)

  • 2024–present: Greater Bay Area Institute of Precision Medicine, Fudan University (Principal Investigator)
  • 2023–2024: Washington University School of Medicine (Staff Scientist)
  • 2020–2023: Washington University School of Medicine & Perelman School of Medicine at the University of Pennsylvania (Postdoctoral Researcher)
  • 2016–2020: University of California, Davis (Ph.D.)
  • 2014–2016: The University of Akron (M.S.)
  • 2011–2015: Lanzhou University (B.S.)

Email: xieyixuan@ipm.gba.org.cn

Academic Profiles: Greater Bay Area Institute of Precision Medicine | Google Scholar

Current Members
Li Yi (Ph.D. Student)

Li Yi 伊力

(Ph.D. Student Candidate)

  • 2024–present: Fudan University (Ph.D.)
  • 2022–2024: Fudan University (M.S.)
  • 2017–2022: Harbin Medical University (B.S.)

Research Fields: Epitranscriptomics, Bioinformatics

Email: lyi24@m.fudan.edu.cn

jiuyu

JiuYu Jin 金久煜

(Visiting Student, Ph.D. Student Candidate)

  • 2023–present: Lanzhou University (Ph.D.)
  • 2019–2022: Henan University Of Science and Technology (M.S.)
  • 2014–2018: Luoyang Institute of Science and Technology (B.S.)

Research Fields: MALDI imaging, Epitranscriptomics

Email: jinjy2023@lzu.edu.cn

Animal Crossing

Yi Yi

(Yi Yi claims she obtained
Ph.D. degree.)

Bomb and Lee

(Li Yi's Ph.D.-mate.)

News

Enjoy the moment

Software/Database

All resources are available to download for free

Glycan-interactome

The glycan-dependent protein interactome (GDPI) across different glycan phenotypes.

NuMoFinder

A tool to identify and quantify the peaks of nucleic acid modifications referred from Modomics and DNAmod databases

GlycanDIAFinder

Its aim is to analyze Glycosylation with the sensitive data-independent acquisition (DIA) strategy.

EpiProfile

A Computational Platform for Processing Epi-Proteomics Mass Spectrometry Data

Latest Publications

Xie Lab Publications from 2017 to 2024
ALL
2024
Prior to Independent Research
2024

Xie, Y., Liu, X., Zhao, C., Chen, S., Wang, S., Lin, Z., Robison, F. M., George, B. M., Flynn, R. A., Lebrilla, C. B., & Garcia, B. A. (2024), Development and application of GlycanDIA workflow for glycomic analysis. bioRxiv: the preprint server for biology, 2024.03.12.584702.

Liu, X., Yi, L., Lin, Z., Chen, S., Wang, S., Sheng, Y., Lebrilla, C. B., Garcia, B. A., & Xie, Y. (2024), Metabolic control of glycosylation forms for establishing glycan-dependent protein interaction networks. bioRxiv (Cold Spring Harbor Laboratory).

Xie, Y., Brás-Costa, C., Lin, Z., & Garcia, B. A. (2024), Mass spectrometry analysis of nucleic acid modifications: from beginning to future. Mass spectrometry reviews, Advance online publication.

Prior to Independent Research

Xie, Y., Chai, P., Till, N. A., Hemberger, H., Lebedenko, C. G., Porat, J., Watkins, C. P., Caldwell, R. M., George, B. M., Perr, J., Bertozzi, C. R., Garcia, B. A., & Flynn, R. A. (2024), The modified RNA base acp3U is an attachment site for N-glycans in glycoRNA. Cell, 187(19), 5228–5237.e12.

Porat, J., Watkins, C. P., Jin, C., Xie, Y., Tan, X., Lebedenko, C. G., Hemberger, H., Shin, W., Chai, P., Collins, J. J., Garcia, B. A., Bojar, D., & Flynn, R. A. (2024), O-glycosylation contributes to mammalian glycoRNA biogenesis. bioRxiv: the preprint server for biology, 2024.08.28.610074.

Liu, X., Zhang, Y., Wen, Z., Hao, Y., Banks, C. A. S., Cesare, J., Bhattacharya, S., Arvindekar, S., Lange, J. J., Xie, Y., Garcia, B. A., Slaughter, B. D., Unruh, J. R., Viswanath, S., Florens, L., Workman, J. L., & Washburn, M. P. (2024), An integrated structural model of the DNA damage-responsive H3K4me3 binding WDR76:SPIN1 complex with the nucleosome. Proceedings of the National Academy of Sciences of the United States of America, 121(33), e2318601121.

Lin, Z., Xie, Y., Gongora, J., Liu, X., Zahn, E., Palai, B. B., Ramirez, D., Searfoss, R. M., Vitorino, F. N., Dann, G. P., Zhao, C., Han, X., MacTaggart, B., Lan, X., Fu, D., Greenberg, L., Zhang, Y., Lavine, K. J., Greenberg, M. J., Lv, D., … Garcia, B. A. (2024), An unbiased proteomic platform for activity-based arginylation profiling. bioRxiv : the preprint server for biology, 2024.06.01.596974.

Izadifar, Z., Cotton, J., Chen, S., Horvath, V., Stejskalova, A., Gulati, A., LoGrande, N. T., Budnik, B., Shahriar, S., Doherty, E. R., Xie, Y., To, T., Gilpin, S. E., Sesay, A. M., Goyal, G., Lebrilla, C. B., & Ingber, D. E. (2024), Mucus production, host-microbiome interactions, hormone sensitivity, and innate immune responses modeled in human cervix chips. Nature Communications, 15(1), 4578.

Xie, Y., Chen, S., Alvarez, M. R., Sheng, Y., Li, Q., Maverakis, E., & Lebrilla, C. B. (2024), Protein oxidation of fucose environments (POFE) reveals fucose-protein interactions. Chemical Science, 15(14), 5256–5267.

Frisbie, V. S., Hashimoto, H., Xie, Y., De Luna Vitorino, F. N., Baeza, J., Nguyen, T., Yuan, Z., Kiselar, J., Garcia, B. A., & Debler, E. W. (2024), Two DOT1 enzymes cooperatively mediate efficient ubiquitin-independent histone H3 lysine 76 tri-methylation in kinetoplastids. Nature Communications, 15(1), 2467.

Lin, Z., Gongora, J., Liu, X., Xie, Y., Zhao, C., Lv, D., & Garcia, B. A. (2023), Automation to enable high-throughput chemical proteomics. Journal of Proteome Research, 22(12), 3676–3682.

Lu-Culligan, W. J., Connor, L. J., Xie, Y., Ekundayo, B. E., Rose, B. T., Machyna, M., Pintado-Urbanc, A. P., Zimmer, J. T., Vock, I. W., Bhanu, N. V., King, M. C., Garcia, B. A., Bleichert, F., & Simon, M. D. (2023), Acetyl-methyllysine marks chromatin at active transcription start sites. Nature, 622(7981), 173–179.

Chen, S., Bouchibti, Y., Xie, Y., Chen, Y., Chang, V., & Lebrilla, C. B. (2023), Analysis of cell glycogen with quantitation and determination of branching using liquid chromatography-mass spectrometry. Analytical Chemistry, 95(34), 12884–12892.

Lauman, R., Kim, H. J., Pino, L. K., Scacchetti, A., Xie, Y., Robison, F., Sidoli, S., Bonasio, R., & Garcia, B. A. (2023). Expanding the epitranscriptomic RNA sequencing and modification mapping mass spectrometry toolbox with field asymmetric waveform ion mobility and electrochemical elution liquid chromatography. Analytical Chemistry, 95(12), 5187–5195.

Alvarez, M. R., Zhou, Q., Tena, J., Barboza, M., Wong, M., Xie, Y., Lebrilla, C. B., Cabanatan, M., Barzaga, M. T., Tan-Liu, N., Heralde, F. M., 3rd, Serrano, L., Nacario, R. C., & Completo, G. C. (2023). Glycomic, glycoproteomic, and proteomic profiling of philippine lung cancer and peritumoral tissues: case series study of patients stages I–III. Cancers, 15(5), 1559.

Xie, Y., De Luna Vitorino, F. N., Chen, Y., Lempiäinen, J. K., Zhao, C., Steinbock, R. T., Lin, Z., Liu, X., Zahn, E., Garcia, A. L., Weitzman, M. D., & Garcia, B. A. (2023). SWAMNA: a comprehensive platform for analysis of nucleic acid modifications. Chemical Communications (Cambridge, England), 59(83), 12499–12502.

Merleev, A. A., Le, S. T., Alexanian, C., Toussi, A., Xie, Y., Marusina, A. I., Watkins, S. M., Patel, F., Billi, A. C., Wiedemann, J., Izumiya, Y., Kumar, A., Uppala, R., Kahlenberg, J. M., Liu, F. T., Adamopoulos, I. E., Wang, E. A., Ma, C., Cheng, M. Y., Xiong, H., … Maverakis, E. (2022), Biogeographic and disease-specific alterations in epidermal lipid composition and single-cell analysis of acral keratinocytes. JCI Insight, 7(16), e159762.

Xie, Y., Janssen, K. A., Scacchetti, A., Porter, E. G., Lin, Z., Bonasio, R., & Garcia, B. A. (2022), Permethylation of ribonucleosides provides enhanced mass spectrometry quantification of post-transcriptional RNA modifications. Analytical Chemistry, 94(20), 7246–7254.

Janssen, K. A., Xie, Y., Kramer, M. C., Gregory, B. D., & Garcia, B. A. (2022), Data-independent acquisition for the detection of mononucleoside RNA modifications by mass spectrometry. Journal of the American Society for Mass Spectrometry, 33(5), 885–893.

Sheng, Y., Vinjamuri, A., Alvarez, M. R. S., Xie, Y., McGrath, M., Chen, S., Barboza, M., Frieman, M., & Lebrilla, C. B. (2022), Host cell glycocalyx remodeling reveals SARS-CoV-2 Spike protein glycomic binding sites. Frontiers in Molecular Biosciences, 9, 799703.

Li, Q., Xie, Y., Rice, R., Maverakis, E., & Lebrilla, C. B. (2022), A proximity labeling method for protein-protein interactions on cell membrane. Chemical Science, 13(20), 6028–6038.

Kim, T., Xie, Y., Li, Q., Artegoitia, V. M., Lebrilla, C. B., Keim, N. L., Adams, S. H., & Krishnan, S. (2021), Diet affects glycosylation of serum proteins in women at risk for cardiometabolic disease. European Journal of Nutrition, 60(7), 3727–3741.

Zhou, Q., Xie, Y., Lam, M., & Lebrilla, C. B. (2021), N-Glycomic analysis of the cell shows specific effects of glycosyl transferase inhibitors. Cells, 10(9), 2318.

Maverakis, E., Merleev, A. A., Park, D., Kailemia, M. J., Xu, G., Ruhaak, L. R., Kim, K., Hong, Q., Li, Q., Leung, P., Liakos, W., Wan, Y. Y., Bowlus, C. L., Marusina, A. I., Lal, N. N., Xie, Y., Luxardi, G., & Lebrilla, C. B. (2021), Glycan biomarkers of autoimmunity and bile acid-associated alterations of the human glycome: primary biliary cirrhosis and primary sclerosing cholangitis-specific glycans. Clinical Immunology, 230, 108825.

Zheng, J. J., Agus, J. K., Hong, B. V., Tang, X., Rhodes, C. H., Houts, H. E., Zhu, C., Kang, J. W., Wong, M., Xie, Y., Lebrilla, C. B., Mallick, E., Witwer, K. W., & Zivkovic, A. M. (2021), Isolation of HDL by sequential flotation ultracentrifugation followed by size exclusion chromatography reveals size-based enrichment of HDL-associated proteins. Scientific Reports, 11(1), 16086.

Xie, Y., Chen, S., Li, Q., Sheng, Y., Alvarez, M. R., Reyes, J., Xu, G., Solakyildirim, K., & Lebrilla, C. B. (2021), Glycan-protein cross-linking mass spectrometry reveals sialic acid-mediated protein networks on cell surfaces. Chemical Science, 12(25), 8767–8777.

Kasper, D. M., Hintzen, J., Wu, Y., Ghersi, J. J., Mandl, H. K., Salinas, K. E., Armero, W., He, Z., Sheng, Y., Xie, Y., Heindel, D. W., Park, E. J., Sessa, W. C., Mahal, L. K., Lebrilla, C., Hirschi, K. K., & Nicoli, S. (2020), The N-glycome regulates the endothelial-to-hematopoietic transition. Science, 370(6521), 1186–1191.

Merleev, A. A., Park, D., Xie, Y., Kailemia, M. J., Xu, G., Ruhaak, L. R., Kim, K., Hong, Q., Li, Q., Patel, F., Wan, Y. Y., Marusina, A. I., Adamopoulos, I. E., Lal, N. N., Mitra, A., Le, S. T., Shimoda, M., Luxardi, G., Lebrilla, C. B., & Maverakis, E. (2020), A site-specific map of the human plasma glycome and its age and gender-associated alterations. Scientific Reports, 10(1), 17505.

Park, S., Doherty, E. E., Xie, Y., Padyana, A. K., Fang, F., Zhang, Y., Karki, A., Lebrilla, C. B., Siegel, J. B., & Beal, P. A. (2020), High-throughput mutagenesis reveals unique structural features of human ADAR1. Nature Communications, 11(1), 5130.

Li, Q., Xie, Y., Wong, M., Barboza, M., & Lebrilla, C. B. (2020), Comprehensive structural glycomic characterization of the glycocalyxes of cells and tissues. Nature Protocols, 15(8), 2668–2704.

Xie, Y., Sheng, Y., Li, Q., Ju, S., Reyes, J., & Lebrilla, C. B. (2020), Determination of the glycoprotein specificity of lectins on cell membranes through oxidative proteomics. Chemical Science, 11(35), 9501–9512.

Li, Q., Xie, Y., Wong, M., & Lebrilla, C. B. (2019). Characterization of cell glycocalyx with mass spectrometry methods. Cells, 8(8), 882.

Li, Q., Xie, Y., Xu, G., & Lebrilla, C. B. (2019). Identification of potential sialic acid binding proteins on cell membranes by proximity chemical labeling. Chemical Science, 10(24), 6199–6209.

Xie, Y., Peng, C., Gao, Y., Liu, X., Liu, T., & Joy, A. (2017). Mannose-based graft polyesters with tunable binding affinity to concanavalin A. Journal of Polymer Science Part A: Polymer Chemistry, 55, 3908-3917.

Available Positions

If you are interested in our research, feel free to contact us anytime

Postdoctoral Researchers

We are seeking outstanding postdoctoral researchers interested in a stimulating training environment to expand their expertise in mass spectrometry and glycosylation research. We welcome postdoctoral candidates with diverse training backgrounds, including but not limited to: Mass Spectrometry, Glycobiology, Epitranscriptomics, Epigenetics, Biochemistry, and Molecular Biology. Interested candidates should submit their CVs, including the names and contact information for two references, along with a brief description of their doctoral training and research goals, to Dr. Yixuan Xie (xieyixuan@ipm-gba.org.cn).

More information

Graduate/Undergraduate Students

We are also looking for motivated graduate students with a passion for applying mass spectrometry-based technologies to solve complex biological questions related to glycosylation. At the same time, limited research positions are available for undergraduate students interested in summer or academic-year research projects. Interested students can email Dr. Yixuan Xie (xieyixuan@ipm-gba.org.cn) to inquire about potential projects and the opportunity to join the lab.

🏢 Address

State Key Laboratory of Genetic Engineering,
Greater Bay Area Institute of Precision Medicine (Guangzhou),
School of Life Sciences and Institutes of Biomedical Sciences,
Fudan University,
Shanghai,
China