Michael Boyce

Overview:

The Boyce Lab studies mammalian cell signaling through protein glycosylation. For the latest news, project information and publications from our group, please visit our web site at http://www.boycelab.org or follow us on Twitter at https://twitter.com/BoyceLab.

Positions:

Associate Professor of Biochemistry

Biochemistry
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2005

Harvard Medical School

Grants:

Control of COPII vesicle trafficking by intracellular protein glycosylation

Administered By
Biochemistry
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Protein glycosylation in cancer cell signaling and metabolism

Administered By
Biochemistry
Role
Principal Investigator
Start Date
End Date

Control of COPII vesicle trafficking by intracellular protein glycosylation

Administered By
Biochemistry
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

The human UDP-galactose 4'-epimerase (GALE) is required for cell-surface glycome structure and function.

Glycan biosynthesis relies on nucleotidesugars (NS), abundant metabolites that serve as monosaccharide donors for glycosyltransferases. In vivo, signal-dependent fluctuations in NS levels are required to maintain normal cell physiology and are dysregulated in disease, but how mammalian cells regulate NS levels and pathway flux remains largely uncharacterized. To address this knowledge gap, we examined uridine diphosphate (UDP)-galactose 4'-epimerase (GALE), which interconverts two pairs of essential NSs. GALE deletion in human cells triggered major imbalances in its substrate NSs and consequent dramatic changes in glycolipids and glycoproteins, including a subset of integrins and the death receptor Fas. NS dysregulation also directly impacted cell signaling, as GALE-/- cells exhibit Fas hypoglycosylation and hypersensitivity to Fas ligand-induced apoptosis. Our results reveal a new role for GALE-mediated NS regulation in supporting death receptor signaling and may have implications for the molecular etiology of illnesses characterized by NS imbalances, including galactosemia and metabolic syndrome.
Authors
Broussard, A; Florwick, A; Desbiens, C; Nischan, N; Robertson, C; Guan, Z; Kohler, JJ; Wells, L; Boyce, M
MLA Citation
Broussard, Alex, et al. “The human UDP-galactose 4'-epimerase (GALE) is required for cell-surface glycome structure and function..” J Biol Chem, Dec. 2019. Pubmed, doi:10.1074/jbc.RA119.009271.
URI
https://scholars.duke.edu/individual/pub1423433
PMID
31819007
Source
pubmed
Published In
The Journal of Biological Chemistry
Published Date
DOI
10.1074/jbc.RA119.009271

Glycosylation of gigaxonin regulates intermediate filaments: Novel molecular insights into giant axonal neuropathy: supplemental information

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-beta-N-acetylglucosamine (O-GlcNAc), a prevalent form of intracellular glycosylation, in a nutrient- and growth factor-dependent manner. Mass spectrometry analyses of human gigaxonin revealed nine candidate sites of O-GlcNAcylation, two of which - serine 272 and threonine 277 - are required for its ability to mediate IF turnover in novel gigaxonin-deficient human cell models that we created. Taken together, these 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 non-genetic modifiers of GAN phenotypes and for the optimization of gene therapy for this disease.
Authors
CHEN, PO-HAN; Smith, T; Hu, J; Pan, S; Smith, A; Lu, A; Chi, J-T; Boyce, M
URI
https://scholars.duke.edu/individual/pub1425510
Source
epmc
Published Date
DOI
10.1101/530303

Directing Traffic: Regulation of COPI Transport by Post-translational Modifications

© Copyright © 2019 Luo and Boyce. The coat protein complex I (COPI) is an essential, highly conserved pathway that traffics proteins and lipids between the endoplasmic reticulum (ER) and the Golgi. Many aspects of the COPI machinery are well understood at the structural, biochemical and genetic levels. However, we know much less about how cells dynamically modulate COPI trafficking in response to changing signals, metabolic state, stress or other stimuli. Recently, post-translational modifications (PTMs) have emerged as one common theme in the regulation of the COPI pathway. Here, we review a range of modifications and mechanisms that govern COPI activity in interphase cells and suggest potential future directions to address as-yet unanswered questions.
Authors
Luo, PM; Boyce, M
MLA Citation
Luo, P. M., and M. Boyce. “Directing Traffic: Regulation of COPI Transport by Post-translational Modifications.” Frontiers in Cell and Developmental Biology, vol. 7, Sept. 2019. Scopus, doi:10.3389/fcell.2019.00190.
URI
https://scholars.duke.edu/individual/pub1415390
Source
scopus
Published In
Frontiers in Cell and Developmental Biology
Volume
7
Published Date
DOI
10.3389/fcell.2019.00190

A chemical glycoproteomics platform reveals O-GlcNAcylation of mitochondrial voltage-dependent anion channel 2.

Protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc) is a critical cell signaling modality, but identifying signal-specific O-GlcNAcylation events remains a significant experimental challenge. Here, we describe a method for visualizing and analyzing organelle- and stimulus-specific O-GlcNAcylated proteins and use it to identify the mitochondrial voltage-dependent anion channel 2 (VDAC2) as an O-GlcNAc substrate. VDAC2(-/-) cells resist the mitochondrial dysfunction and apoptosis caused by global O-GlcNAc perturbation, demonstrating a functional connection between O-GlcNAc signaling and mitochondrial physiology through VDAC2. More broadly, our method will enable the discovery of signal-specific O-GlcNAcylation events in a wide array of experimental contexts.
Authors
Palaniappan, KK; Hangauer, MJ; Smith, TJ; Smart, BP; Pitcher, AA; Cheng, EH; Bertozzi, CR; Boyce, M
MLA Citation
Palaniappan, Krishnan K., et al. “A chemical glycoproteomics platform reveals O-GlcNAcylation of mitochondrial voltage-dependent anion channel 2..” Cell Rep, vol. 5, no. 2, Oct. 2013, pp. 546–52. Pubmed, doi:10.1016/j.celrep.2013.08.048.
URI
https://scholars.duke.edu/individual/pub967790
PMID
24120863
Source
pubmed
Published In
Cell Reports
Volume
5
Published Date
Start Page
546
End Page
552
DOI
10.1016/j.celrep.2013.08.048

Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury.

The mechanism of apoptosis has been extensively characterized over the past decade, but little is known about alternative forms of regulated cell death. Although stimulation of the Fas/TNFR receptor family triggers a canonical 'extrinsic' apoptosis pathway, we demonstrated that in the absence of intracellular apoptotic signaling it is capable of activating a common nonapoptotic death pathway, which we term necroptosis. We showed that necroptosis is characterized by necrotic cell death morphology and activation of autophagy. We identified a specific and potent small-molecule inhibitor of necroptosis, necrostatin-1, which blocks a critical step in necroptosis. We demonstrated that necroptosis contributes to delayed mouse ischemic brain injury in vivo through a mechanism distinct from that of apoptosis and offers a new therapeutic target for stroke with an extended window for neuroprotection. Our study identifies a previously undescribed basic cell-death pathway with potentially broad relevance to human pathologies.
Authors
Degterev, A; Huang, Z; Boyce, M; Li, Y; Jagtap, P; Mizushima, N; Cuny, GD; Mitchison, TJ; Moskowitz, MA; Yuan, J
MLA Citation
Degterev, Alexei, et al. “Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury..” Nat Chem Biol, vol. 1, no. 2, July 2005, pp. 112–19. Pubmed, doi:10.1038/nchembio711.
URI
https://scholars.duke.edu/individual/pub808787
PMID
16408008
Source
pubmed
Published In
Nature Chemical Biology
Volume
1
Published Date
Start Page
112
End Page
119
DOI
10.1038/nchembio711