Christopher West

Research

We are interested in how unicellular eukaryote parasites exploit protein glycosylation to conduct their business, either by modifying their own glycosylation, or employing glycan recognition to access their hosts. Our general attention is directed to the evolution and function of parasite glycosyltransferases, utilizing biochemistry in conjunction with gene editing and glycomic profiling to elucidate enzymatic and cellular roles. This has led to the elucidation of several novel processes within our lab and through collaborations, some of which have been shown to support important cellular functions.

A major finding has led to the discovery of an oxygen sensing pathway in the highly successful apicomplexan parasite Toxoplasma gondii. After describing a novel form of glycosylation of a primary polyubiquitin ligase involved in regulation of protein turnover, we found that its anchorage to a hydroxyproline residue depends on an oxygen-dependent prolyl hydroxylase. This enzyme is a homolog of a primary oxygen sensor in human hosts, which functions via a transcription factor (HIF) instead of ubiquitin ligases. These discoveries have led to identification of an additional prolyl hydroxylase, which together with the first affect parasite trafficking and virulence in a mouse model. These studies in collaboration with Ira Blader (Virginia Tech) have uncovered a new area of investigation of the impact of environmental factors on parasite biology and virulence, which applies also to a range of other protist pathogens and model organisms.

A second and recent finding is the discovery, with our collaborator John Samuelson (Boston University), of a prevalent form on mono-fucosylation of nucleocytoplasmic proteins. Based on genetic manipulation of the O-fucosyltransferase, we know that O-fucose supports the cellular abundance of multiple parasite proteins important for Toxoplasma fitness. The predicted occurrence of O-fucosylation in a range of other parasites is complementary to O-GlcNAcylation that occurs in animal hosts, suggesting parallel yet potentially distinct roles in stress resistance and nutrient sensing.

Recent Publications

• Kim, H.W., A. Eletsky, K.J. Gonzales, H. van der Wel, E.-M. Strauch, J.H. Prestegard & C.M. West (2020) Skp1 dimerization blocks F-box protein binding. Biochemistry 59:1527-1536. PMCID: PMC7521599 https://doi.org/10.1021/acs.biochem.0c00094
• Mandalasi, M., H.W. Kim, D. Thieker, M.O. Sheikh, E. Gas-Pascual, K. Rahman, P. Zhao, N.G. Daniel, H. van der Wel, T.H. Ichikawa, J.N. Glushka, L. Wells, R.J. Woods, Z.A. Wood & C.M. West (2020) A terminal α3-galactose modification regulates an E3 ubiquitin ligase subunit in Toxoplasma gondii. J. Biol. Chem. 295:9223-9243. PMCID: PMC7335778 https://doi.org/10.1074/jbc.RA120.013792
• Liu, T, M.I. Abboud, R. Chowdhury, A. Tumber, A.P. Hardy, K. Lipp, C.T. Lohans, E. Pires, J. Wickens, M.A. McDonough, C.M. West & C.J. Schofield (2020) Biochemical and biophysical analyses of hypoxia sensing prolyl hydroxylases from Dictyostelium discoideum and Toxoplasma gondii. J. Biol. Chem. 295:16545-16561. PMCID: PMC7864055 https://doi.org/10.1074/jbc.RA120.013998
• West, C.M., D. Malzl, A. Hykollari & I.B.H. Wilson (2021) Glycomics, glycoproteomics and glycogenomics: An inter-taxa evolutionary perspective. Mol. Cell. Proteomics 20:100024. PMCID: PMC8724618 https://doi.org/10.1074/mcp.R120.002263
• Bandini, G., C. Agop-Nersesian, H. van der Wel, M. Mandalasi, H.W. Kim, C.M. West & J. Samuelson (2021) The nucleocytosolic O-fucosyltransferase Spindly affects protein expression and virulence in Toxoplasma gondii. J. Biol. Chem. 296:100039. PMCID: PMC7949088 https://doi.org/10.1074/jbc.RA120.015883
• Boland, A.W., E. Gas-Pascual, B.L. Nottingham, H. van der Wel, M.O. Sheikh, C.M. Schafer & C.M. West (2022) Oxygen-dependent regulation of E3(SCF)ubiquitin ligases and a Skp1-associated JmjD6 homolog in Dictyostelium development. J. Biol. Chem. 298:102305. PMCID: PMC9485057 https://doi.org/10.1016/j.jbc.2022.102305
• West, C.M., C. Slawson, N.E. Zachara & G.W. Hart (2022) Nucleocytoplasmic Glycosylation. In: Varki, A., Cummings, R.D., Esko, J.D., Stanley, P., Hart, G.W., Aebi, M., Mohnen, D., Kinoshita, T., Packer, N.H., Prestegard, J.H., Schnaar, R.L., Seeberger, P.H., editors. Essentials of Glycobiology [Internet]. 4th edition. Cold Spring Harbor Laboratory Press; Chapter 18. Bookshelf ID: NBK579979 https://www.ncbi.nlm.nih.gov/books/NBK579979/
• van der Wel, H., A.M. Garcia, E. Gas-Pascual, M.M. Willis, H. Kim, G. Bandini, M.M Gaye, C.E. Costello, J. Samuelson & C.M. West (2023) Spindly is a nucleocytosolic O-fucosyltransferase in Dictyostelium and related proteins are widespread in protists and bacteria. Glycobiology 33:225-244. PMCID: PMC10114647 https://doi.org/10.1093/glycob/cwac071
• Benbrook, D.M., W. Deng, M.A. Gold, R. Rai, R. Conrad, H. van der Wel, S. Husain, K. Moore, N. Spirtos, A. Jackson, M. Zakhour, C.A. Mathews & C.M. West (2023) Association of Sialyl Tn antigen with cervical cancer lymph node status: an NRG Oncology/GOG study. Gynecologic Oncol. 171:67-75. PMCID: PMC10040434 https://doi.org/10.1016/j.ygyno.2023.02.001
• Boland, A.W., E. Gas-Pascual, H. van der Wel, H.W. Kim & C.M. West (2023) Synergy between a cytoplasmic vWFA/VIT protein and a WD40-repeat F-box protein controls development in Dictyostelium. Front. Cell Dev. Biol. 11:1259844. PMCID: PMC10539598 https://doi.org/10.3389/fcell.2023.1259844
• Cordonnier, C., M. Mandalasi, J. Gigley, E.A. Wohlfert, C.M. West & I.J. Blader (2024) The Toxoplasma oxygen sensing protein, TgPhyA, is required for resistance to interferon-gamma mediated nutritional immunity. PLoS Biol. 22(6): e3002690. PMCID: PMC11192375 https://doi.org/10.1371/journal.pbio.3002690
• Baptista, C.G., S. Hosking, E. Gas-Pascual, L. Ciampossine, S. Abel, M.-A. Hakimic, V. Jeffers, K. Le Roch, C.M. West & I.J. Blader (2024) Toxoplasma gondii F-box protein L2 silences feline-restricted genes necessary for sexual commitment. PLoS Pathogens 20(5): e1012269. PMCID: PMC11166348 https://doi.org/10.1371/journal.ppat.1012269
• Alvarez, J.A., E. Gas-Pascual, S. Malhi, F.N. Njume, J.C. Sánchez-Arcila, H. van der Wel, Y. Zhao, G. Ceron, J. Posada, S.P. Souza, G.S. Yap, C.M. West & K.D.C. Jensen (2024) The GPI sidechain of Toxoplasma gondii inhibits parasite pathogenesis. mBio 15(10):e0052724. PMCID: PMC11481522 https://doi.org/10.1128/mbio.00527-24
• Mandalasi, M.N., E. Gas-Pascual, C.G. Baptista, B. Deng, H. van der Wel, J.A.W. Kruijtzer, G.-J. Boons, I.J. Blader & C.M. West (2024) Oxygen-dependent regulation of F-box proteins in Toxoplasma gondii is mediated by Skp1 glycosylation. J. Biol. Chem. 300(11):107801. PMCID: PMC11570480 https://doi.org/10.1016/j.jbc.2024.107801*Designated ‘Editor’s Choice’
• Sreenivasamurthy, S.K., C.G. Baptista, C.M. West, I.J. Blader & J.D. Dvorin (2025) PfFBXO1 is essential for inner membrane complex formation in Plasmodium falciparum during both asexual and transmission stages. Communications Biology 8(1):190. PMCID: PMC11802861 https://doi.org/10.1038/s42003-025-07619-6
• Fu, Y., T. Tomita, L.M Weiss, C.M West & L.D. Sibley (2025) Toxoplasma chitinase-like protein orchestrates cyst wall glycosylation to facilitate effector export and cyst turnover. Proc. Natl. Acad. Sci., USA 122(5):e2416870122. PMCID: PMC11804682 https://doi.org/10.1073/pnas.2416870122
• Tiwari, M., E. Gas-Pascual, M. Goyal, M. Popov, N. Olszewski, K. Matsumoto, R.S. Haltiwanger, M. Grafe, R. Graf, R. Orlando, J. Samuelson & C.M. West (2025) Novel antibody detection of nucleocytoplasmic O-fucose reveals widespread and developmentally regulated expression in protist pathogens, cellular slime molds and plants. mSphere 10(2):e0094524. PMCID: PMC11853108 https://doi.org/10.1128/msphere.00945-24
• Cantrell, D.A., R.J.B. Urbauer, H.W. Kim, R.J. Woods, J.L. Urbauer, Z.A. Wood & C.M. West (2025) Glycosylation weakens Skp1 homodimerization in Toxoplasma gondii by interrupting a fuzzy interaction. Biochemistry 64(10):2262-2279. PMCID: PMC12101541 https://doi.org/10.1021/acs.biochem.4c00859
• Tiwari, M., E. Gas-Pascual, J. Teal-Urquides, J. Samuelson & C.M. West (2025) O-fucosylation affects abundance but not localization of select nucleocytoplasmic proteins in Toxoplasma gondii. Glycobiology 35:cwaf051. PMCID: PMC12449179 https://doi.org/10.1093/glycob/cwaf051
• Hesnard, J., E. Gas-Pascual, H. van der Wel, O. Cochet-Escartin, S. Joly, J.-P. Rieu, C.M. West & C. Anjard (2025) Global characterization of Dictyostelium discoideum gene expression changes under hypoxic conditions. bioRxiv, DOI: 10.1101/2025.04.02.646759 https://doi.org/10.1101/2025.04.02.646759
• Cantrell, D.A., H. van der Wel, & C.M. West (2025) Glycoregulation of E3(SCF) ubiquitin ligases in unicellular eukaryotes. Glycobiology, submitted.

News

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