SipioneLAB
UNIVERSITY OF ALBERTA
Selected Publications
Schmidt EN, Lamprinaki D, McCord KA, Joe M, Sojitra M, Waldow A, Nguyen J, Monyror J, Kitova EN, Mozaneh F, Guo XY, Jung J, Enterina JR, Daskhan GC, Han L, Krysler AR, Cromwell CR, Hubbard BP, West LJ, Kulka M, Sipione S, Klassen JS, Derda R, Lowary TL, Mahal LK, Riddell MR, Macauley MS (2023). Siglec-6 mediates the uptake of extracellular vesicles through a noncanonical glycolipid binding pocket. Nat Commun. 14(1):2327. doi: 10.1038/s41467-023-38030-6
de Almeida MMA, Watson AES, Bibi S, Dittmann NL, Goodkey K, Sharafodinzadeh P, Galleguillos D, Nakhaei-Nejad M, Kosaraju J, Steinberg N, Wang BS, Footz T, Giuliani F, Wang J, Sipione S, Edgar JM, Voronova A (2023). Fractalkine enhances oligodendrocyte regeneration and remyelination in a demyelination mouse model.Stem Cell Reports:18(2):519-533. doi: 10.1016/j.stemcr.2022.12.001.
Viveiros A, Kadam V, Monyror J, Morales LC, Pink D, Rieger AM, Sipione S* and Posse de Chaves E* (2022). In-Cell Labeling Coupled to Direct Analysis of Extracellular Vesicles in the Conditioned Medium to Study Extracellular Vesicles Secretion with Minimum Sample Processing and Particle Loss. Cells 2022, 11(3), 351; https://doi.org/10.3390/cells11030351
Galleguillos D, Wang Q, Steinberg N, Shrivastava G, Dhami K, Daskhan GC, Schmidt EN, Dworsky-Fried Z, Giuliani F, Churchward M, Power C, Todd K, Taylor A, Macauley MS, Sipione S (2022). Anti-inflammatory role of GM1 and modulatory effects of gangliosides on microglia functions. J Neuroinflammation, 19(1):9. doi: 10.1186/s12974-021-02374-x
In this paper we describe novel modulatory and anti-inflammatory effects of gangliosides on microglia cells, the immune cells of the brain. These findings have potential therapeutic implications in neurodegenerative and neuroinflammatory diseases.
Sipione S, Monyror J, Galleguillos D, Steinberg N, Kadam V (2020).Gangliosides
in the brain: Physiology, pathophysiology and therapeutic applications. Frontiers in
Neuroscience, 2020 Oct 6;14:572965.
Bhattacherjee A, Rodrigues E, Jung J, Luzentales-Simpson M, Enterina JR, , St Laurent CD, Nakhaei-Nejad M, Fuchsberger FF, Streith L, Wang Q, Kawasaki N, Duan S, Bains A, Paulson JC, Rademacher C, Giuliani F, Sipione S, Macauley MS (2019). Repression of phagocytosis by human CD33 is not conserved with mouse CD33. Commun Biol. 2019 Dec 3;2:450.
Di Pardo A, Monyror J, Morales LC, Kadam V, Lingrell S, Maglione V,Wozniak RW,
Sipione S (2019) Mutant huntingtin interacts with the sterol regulatory element-binding
proteins and impairs their nuclear import. Hum Mol Genet., 2020 Feb 1;29(3):418-431.
Magistretti PJ, Geisler FH, Schneider JS, Li PA, Fiumelli H, Sipione S (2019).
Gangliosides: Treatment avenues in neurodegenerative disease. Front Neurol.,
10:859, doi: 10.3389/fneur.2019.00859.
Van der Veen JN, Lingrell S, McCloskey N, LeBlond ND, Galleguillos D, Zhao YY, Curtis JM, Sipione S, Fullerton MD, Vance DE, Jacobs RL (2019). A role for phospatidylcholine and phosphatidylethanolamine in hepatic insulin signaling. Jan 7:fj201802117R. doi: 10.1096/fj.201802117R.
Baronas VA, Yang RY, Morales LC, Sipione S and Kurata HT (2018). Slc7a5 modifies the functional outcome of epilepsy-linked Kv1.2 channel mutations. Nature Commun., 9(1):4417.
Bowie LE, Maiuri T, Alpaugh M, Gabriel M, Arbez N, Galleguillos D,Hung CLK,
Patel S, Xia J, Hertz NT, Ross CA, Litchfield DW, Sipione S, Truant R (2018)
N6-Furfuryladenine is protective in Huntington’s disease models by signaling
huntingtin phosphorylation. PNAS, 115(30):E7081-E7090.
Alpaugh M, Galleguillos D, Forero J, Morales LC, Lackey SW, Kar P,Di Pardo A,
Holt A, Kerr B, Todd KG, Baker GB, Fouad K and Sipione S (2017) Disease-modifying
effects of ganglioside GM1 in Huntington’s disease models. EMBO Mol. Med.,
9 (11):1537-1557.
Han L, Morales LC, Richards MR, Kitova EN, Sipione S, Klassen JS (2017) Investigating the influence of membrane composition on protein-glycolipid binding using nanodiscs and proxy ligand electrospray ionization mass spectrometry. , Sep 5;89(17):9330-38.
Wei D, Hurd C, D. Galleguillos, Singh J, Fenrich KK, Webber CA, Sipione S and Fouad K (2016) Inhibiting cortical protein kinase A in spinal cord injured rats enhances efficacy of rehabilitative training. , 283(Pt A):365-74.
Mejia EM, Chau S, Sparagna GC, Sipione S and Hatch GM (2016) Reduced mitochondrial function in Human Huntington disease lymphoblasts is not due to alterations in cardiolipin metabolism or mitochondrial supercomplex assembly. Lipids, 51 (5):561-9.
Lian j, Wei E, Wang S. Quiroga A, Li L, Di Pardo A, van der Veen J, Sipione S, Mitchell G and Lehner R. (2012) Liver specific inactivation of carboxylesterase 3/triacylglycerol hydrolase decreases blood lipids without causing severe steatosis. Hepatology, 56(6):2154-62.
Weishaupt N, Mason AL, Hurd C, May Z, Zmyslowski DC, Galleguillos D, Sipione S and Fouad K (2014) Vector-induced NT-3 expression in rats promotes collateral growth of injured corticospinal tract axons far rostral to a spinal cord injury. 272:65-75.
Weishaupt N, Li S, Di Pardo A, Sipione S and Fouad K (2013) Synergistic effects of BDNF and rehabilitative training on recovery after cervical spinal cord injury. Behav Brain Res. 2013 Feb 15;239:31-42.239:31-42.
Mohamed A, Saavedra L, Di Pardo A, Sipione S and Posse de Chaves E (2012). β-Amyloid Inhibits Protein Prenylation and Induces Cholesterol Sequestration by Impairing SREBP-2 Cleavage. J Neurosci. 9;32(19):6490-500.
Di Pardo A, Maglione V, Alpaugh M, Horkey M, Atwal RS, Sassone J,
Ciammola A, Steffan JS, Fouad K, Truant R and Sipione S (2012) Ganglioside GM1
induces phosphorylation of mutant huntingtin and restores motor behavior in
Huntington disease mice. PNAS, 109(9):3528-33.
Atwal RS, Desmond DR, Caron N, Maiuri T, Xia J, Sipione S and Truant R (2011) Kinase inhibitors modulate huntingtin cell localization and toxicity.
Nat. Chem. Biol., 7(7):453-60.
Maglione V, Marchi P, Di Pardo A, Lingrell S, Horkey M, Tidmarsh E and
Sipione S. (2010) Impaired ganglioside metabolism in Huntington’s disease and
neuroprotective role of GM1. J. Neurosci., 17(11):4072-80.
Posse de Chaves E and Sipione S (2010) Sphingolipids and gangliosides of the nervous system in membrane function and dysfunction. FEBS Lett., 584(9):1748-59.
Here, we uncover the mechanism that leads to cholesterol biosynthesis dysregulation in Huntington's disease, an important player in HD pathogenesis.
This review covers the biology of gangliosides with a specific focus on their role in brain cells and neurodegenerative conditions. It also discusses studies, models and clinical trials where gangliosides have been shown to have neuroprotective effects.
This paper provides an extensive review of all clinical trials performed with ganglioside GM1 in conditions that span from stroke to PD and spinal cord injury. It also highlights preclinical studies in models of neurodegenerative disorders.
This paper describes the therapeutic effects of an ATP analogue, N6-furfuryladenine, in models of HD and the involvement of DNA damage responses in the pathogenesis of HD. It has implications for the potential treatment of HD in patients.
This seminal paper demonstrates that ganglioside GM1 has dramatic therapeutic effects in three different mouse models of HD. Not only GM1 abrogates disease symptoms, but it also slows down neurodegeneration and decreases the levels of toxic mutant HTT.
This seminal paper shows, for the first time, that GM1 has therapeutic effects in a mouse model of HD, and that it induces a critical post-translational modification of mutant HTT that makes this protein less toxic.
Here, we discovered the gangliosides are decreased in several HD models and in fibroblasts from HD patients, and that restoring levels of GM1 protects HD cells from apoptosis.