Honors & Awards


  • Phi Beta Kappa, University of California, Los Angeles (2017)
  • Duke International Chancellor’s Scholarship, Duke University (2018)
  • Duke Biosciences Collaborative for Research Engagement (BioCoRE) Scholarship, Duke University (2018)
  • Travel Award, American Society for Biochemistry and Molecular Biology (2020)
  • Duke Scholar in Molecular Medicine Program (Neuroscience), Duke University, Clinical and Translational Science Institute (2022)
  • Graduate Student Research Award, Ruth K. Broad Biomedical Foundation (2022)
  • Trainee Professional Development Award, Society for Neuroscience (2022)
  • Kamin Travel Award, Duke University, department of biochemistry (2022)
  • Graduate School Conference Travel Award, Duke University (2022)
  • Professional Development Award, Duke University (2023)
  • Gerald D. and Ruth L. Fischbach Endowed Scholarship, Marine Biological Laboratory (2023)
  • Ellen Luken Student Award, Ruth K. Broad Biomedical Research Foundation (2023)
  • Graduate Student Pilot Research Grant Award, Precision Genomics Collaboratory, Duke University (2023)
  • Society of General Physiologists Scholar, Marine Biological Laboratory (2023)
  • Weill Institute Emerging Scholar, Cornell University (2023)
  • Dean’s Award for Research Excellence, Duke School of Medicine (2024)
  • DISCOVER award, Salk Institute for Biological Sciences (2024)
  • INSPIRE award, Washington University in Saint Louis, department of neuroscience (2024)
  • Graduate Student Rising Star, University of Utah, department of biochemistry (2024)

Professional Education


  • Doctor of Philosophy, Duke University (2024)
  • BS, University of California, Los Angeles, Biochemistry (2017)

Stanford Advisors


Lab Affiliations


Graduate and Fellowship Programs


All Publications


  • O-GlcNAcylation regulates neurofilament-light assembly and function and is perturbed by Charcot-Marie-Tooth disease mutations. Nature communications Huynh, D. T., Tsolova, K. N., Watson, A. J., Khal, S. K., Green, J. R., Li, D., Hu, J., Soderblom, E. J., Chi, J. T., Evans, C. S., Boyce, M. 2023; 14 (1): 6558

    Abstract

    The neurofilament (NF) cytoskeleton is critical for neuronal morphology and function. In particular, the neurofilament-light (NF-L) subunit is required for NF assembly in vivo and is mutated in subtypes of Charcot-Marie-Tooth (CMT) disease. NFs are highly dynamic, and the regulation of NF assembly state is incompletely understood. Here, we demonstrate that human NF-L is modified in a nutrient-sensitive manner by O-linked-β-N-acetylglucosamine (O-GlcNAc), a ubiquitous form of intracellular glycosylation. We identify five NF-L O-GlcNAc sites and show that they regulate NF assembly state. NF-L engages in O-GlcNAc-mediated protein-protein interactions with itself and with the NF component α-internexin, implying that O-GlcNAc may be a general regulator of NF architecture. We further show that NF-L O-GlcNAcylation is required for normal organelle trafficking in primary neurons. Finally, several CMT-causative NF-L mutants exhibit perturbed O-GlcNAc levels and resist the effects of O-GlcNAcylation on NF assembly state, suggesting a potential link between dysregulated O-GlcNAcylation and pathological NF aggregation. Our results demonstrate that site-specific glycosylation regulates NF-L assembly and function, and aberrant NF O-GlcNAcylation may contribute to CMT and other neurodegenerative disorders.

    View details for DOI 10.1038/s41467-023-42227-0

    View details for PubMedID 37848414

    View details for PubMedCentralID PMC10582078

  • Chemical Biology Approaches to Understanding Neuronal O-GlcNAcylation. Israel journal of chemistry Huynh, D. T., Boyce, M. 2023; 63 (1-2)

    Abstract

    O-linked β-N-acetylglucosamine (O-GlcNAc) is a ubiquitous post-translational modification in mammals, decorating thousands of intracellular proteins. O-GlcNAc cycling is an essential regulator of myriad aspects of cell physiology and is dysregulated in numerous human diseases. Notably, O-GlcNAcylation is abundant in the brain and numerous studies have linked aberrant O-GlcNAc signaling to various neurological conditions. However, the complexity of the nervous system and the dynamic nature of protein O-GlcNAcylation have presented challenges for studying of neuronal O-GlcNAcylation. In this context, chemical approaches have been a particularly valuable complement to conventional cellular, biochemical, and genetic methods to understand O-GlcNAc signaling and to develop future therapeutics. Here we review selected recent examples of how chemical tools have empowered efforts to understand and rationally manipulate O-GlcNAcylation in mammalian neurobiology.

    View details for DOI 10.1002/ijch.202200071

    View details for PubMedID 36874376

    View details for PubMedCentralID PMC9983623

  • Evidence for nutrient-dependent regulation of the COPII coat by O-GlcNAcylation. Glycobiology Bisnett, B. J., Condon, B. M., Linhart, N. A., Lamb, C. H., Huynh, D. T., Bai, J., Smith, T. J., Hu, J., Georgiou, G. R., Boyce, M. 2021; 31 (9): 1102-1120

    Abstract

    O-linked β-N-acetylglucosamine (O-GlcNAc) is a dynamic form of intracellular glycosylation common in animals, plants and other organisms. O-GlcNAcylation is essential in mammalian cells and is dysregulated in myriad human diseases, such as cancer, neurodegeneration and metabolic syndrome. Despite this pathophysiological significance, key aspects of O-GlcNAc signaling remain incompletely understood, including its impact on fundamental cell biological processes. Here, we investigate the role of O-GlcNAcylation in the coat protein II complex (COPII), a system universally conserved in eukaryotes that mediates anterograde vesicle trafficking from the endoplasmic reticulum. We identify new O-GlcNAcylation sites on Sec24C, Sec24D and Sec31A, core components of the COPII system, and provide evidence for potential nutrient-sensitive pathway regulation through site-specific glycosylation. Our work suggests a new connection between metabolism and trafficking through the conduit of COPII protein O-GlcNAcylation.

    View details for DOI 10.1093/glycob/cwab055

    View details for PubMedID 34142147

    View details for PubMedCentralID PMC8457363

  • Kelch-like Proteins Have a Sweet Spot: Site-specific Glycosylation Influences Metabolic Regulation and Protein Homeostasis Huynh, D., Chen, P., Hu, J., Smith, T., Chi, J., Boyce, M. WILEY. 2020
  • Gigaxonin glycosylation regulates intermediate filament turnover and may impact giant axonal neuropathy etiology or treatment. JCI insight Chen, P. H., Hu, J., Wu, J., Huynh, D. T., Smith, T. J., Pan, S., Bisnett, B. J., Smith, A. B., Lu, A., Condon, B. M., Chi, J. T., Boyce, M. 2020; 5 (1)

    Abstract

    Gigaxonin (also known as KLHL16) is an E3 ligase adaptor protein that promotes the ubiquitination and degradation of intermediate filament (IF) proteins. Mutations in human gigaxonin cause the fatal neurodegenerative disease giant axonal neuropathy (GAN), in which IF proteins accumulate and aggregate in axons throughout the nervous system, impairing neuronal function and viability. Despite this pathophysiological significance, the upstream regulation and downstream effects of normal and aberrant gigaxonin function remain incompletely understood. Here, we report that gigaxonin is modified by O-linked β-N-acetylglucosamine (O-GlcNAc), a prevalent form of intracellular glycosylation, in a nutrient- and growth factor–dependent manner. MS analyses of human gigaxonin revealed 9 candidate sites of O-GlcNAcylation, 2 of which — serine 272 and threonine 277 — are required for its ability to mediate IF turnover in gigaxonin-deficient human cell models that we created. Taken together, the results suggest that nutrient-responsive gigaxonin O-GlcNAcylation forms a regulatory link between metabolism and IF proteostasis. Our work may have significant implications for understanding the nongenetic modifiers of GAN phenotypes and for the optimization of gene therapy for this disease.

    View details for DOI 10.1172/jci.insight.127751

    View details for PubMedID 31944090

    View details for PubMedCentralID PMC7030874

  • A 3.8 Å resolution cryo-EM structure of a small protein bound to an imaging scaffold. Nature communications Liu, Y., Huynh, D. T., Yeates, T. O. 2019; 10 (1): 1864

    Abstract

    Proteins smaller than about 50 kDa are currently too small to be imaged at high resolution by cryo-electron microscopy (cryo-EM), leaving most protein molecules in the cell beyond the reach of this powerful structural technique. Here we use a designed protein scaffold to bind and symmetrically display 12 copies of a small 26 kDa protein, green fluorescent protein (GFP). We show that the bound cargo protein is held rigidly enough to visualize it at a resolution of 3.8 Å by cryo-EM, where specific structural features of the protein are visible. The designed scaffold is modular and can be modified through modest changes in its amino acid sequence to bind and display diverse proteins for imaging, thus providing a general method to break through the lower size limitation in cryo-EM.

    View details for DOI 10.1038/s41467-019-09836-0

    View details for PubMedID 31015551

    View details for PubMedCentralID PMC6478846