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Dr Dominic AlonziBack to People

Dominic-Alonzi
Department: Biochemistry

Background

I read Molecular and Cellular Biochemistry at Corpus Christi, Oxford before reading for a DPhil at Linacre College with Dr Terry Butters and Prof Raymond Dwek, CBE, FRS at the Oxford Glycobiology Institute, Department of Biochemistry.

Teaching and Research Interests

I lecture in Glycobiology to Biochemistry undergraduates and teach a variety of cell biology and biological chemistry topics to biochemistry undergraduates via tutorials: enzymes, drug design, virology, protein structure and function, cell membranes and metabolism. I also tutor the medical and biomedical science students at Magdalen.

My research involves working in the field of glycobiology. Glycobiology has made major contributions to understanding concepts in protein folding, immunology and virology, laying the foundations for applying glycobiology to the development of novel strategies for therapeutics. Inhibitors of the glycosylation pathway can perturb glycan dependent protein folding in the ER with clinically relevant broad-spectrum antiviral properties, with a class of small molecule inhibitors known as iminosugars leading the research in this field. I examine how these small molecule inhibitors can have an affect on a number of cellular targets to enhance and elucidate their therapeutic potential and multiple mechanisms of action.

Selected Publications

Structures of mammalian ER α-glucosidase II capture the binding modes of broad-spectrum iminosugar antivirals

Alessandro T. Caputo, Dominic S. Alonzi, Lucia Marti, Ida-Barbara Reca, J. L. Kiappes, Weston B. Struwe, Alice Cross, Souradeep Basu, Edward D. Lowe, Benoit Darlot, Angelo Santino, Pietro Roversi, and Nicole Zitzmann, PNAS 2016 ; published ahead of print July 26, 2016.

Endoplasmic Reticulum Associated Degradation (ERAD) pathway

Glucosylated free oligosaccharides are biomarkers of endoplasmic reticulum alpha-glucosidase inhibition.
D.S. Alonzi, D.C. Neville, R.H. Lachmann, R.A. Dwek and T.D. Butters (2008) Biochem. J., 409, 571-580.

Demonstration that endoplasmic reticulum-associated degradation of glycoproteins can occur downstream of processing by endomannosidase.
N.V. Kukushkin, D.S. Alonzi, R.A. Dwek and T.D. Butters (2011) Biochem. J., 438, 133-142.

Structural and mechanistic insight into N-glycan processing by endo-α-mannosidase. A.J Thompson, R.J. Williams, Z. Hakki, D.S. Alonzi, T. Wennekes, T.M. Gloster, K. Songsrirote, J.E. Thomas-Oates, T.M. Wrodnigg, J. Spreitz, A.E. Stütz, T.D. Butters, S.J. Williams, G.J. Davies. (2012) Proc Natl Acad Sci U S A. 109(3):781-6.

Glycoprotein misfolding in the endoplasmic reticulum: identification of released oligosaccharides reveals a second ER-associated degradation pathway for Golgi-retrieved proteins. D. S. Alonzi, N. V. Kukushkin, S. A. Allman, Z. Hakki, S. J. Williams, L. Pierce, R. A. Dwek and T. D. Butters. Cellular and Molecular Life Sciences (2013) Cell Mol Life Sci. Aug;70(15):2799-814.

Novel Iminosugars as Therapeutic Drugs

Improved cellular inhibitors for glycoprotein processing a-glucosidases: biological characterisation of alkyl- and arylalkyl-N-substituted deoxynojirimycins.
D.S. Alonzi, R.A. Dwek and T.D. Butters (2009) Tetrahedron: Asymmetry, 20, 897-901

Synthesis and biological characterisation of novel N-alkyl-deoxynojirimycin alpha-glucosidase inhibitors.
A.J. Rawlings, H. Lomas, A.W. Pilling, M.J. Lee, D.S. Alonzi, J.S. Rountree, S.F Jenkinson, G.W.J. Fleet, R.A. Dwek, J.H. Jones and T.D. Butters (2009) ChemBioChem, 10, 1101-1105.

Cystic fibrosis and diabetes: isoLAB and isoDAB, enantiomeric carbon-branched pyrrolidine iminosugars.
D. Best, S.F. Jenkinson, A.W. Saville, D.S. Alonzi, M.R. Wormald, T.D. Butters, C. Norez, F. Becq, Y. Blériot, I. Adachi, A. Kato and G.W.J. Fleet (2010) Tetrahedron Letters, 51, 4170-4174.

Therapeutic targets for inhibitors of glycosylation.
D.S. Alonzi and T.D. Butters (2011) Chimia (Aarau), 65, 35-39.

Glycosphingolipid synthesis inhibition limits osteoclast activation and myeloma bone disease.
A. Ersek, K. Xu, A. Antonopoulos, T. D. Butters, A. E. Santo, Y. Vattakuzhi, L. M. Williams, K. Goudevenou, L. Danks, A. Freidin, E. Spanoudakis, S. Parry, M. Papaioannou, E. Hatjiharissi, A. Chaidos, D. S. Alonzi, G. Twigg, M. Hu, R. A. Dwek, S. M. Haslam, I. Roberts, A. Dell, A. Rahemtulla, N. J. Horwood, A. Karadimitris. (2015) J Clin Invest. Jun;125(6):2279-92

Method Developemnt and Glycosylation Biomarkers of disease

Urinary glycan markers for disease.
D.S. Alonzi, Y.-H. Su and T.D. Butters (2011) Biochem. Soc. Trans, 39, 393-398.

Hydrophilic interaction liquid chromatography of anthranilic acid-labelled oligosaccharides with a 4-aminobenzoic acid ethyl ester-labelled dextran hydrolysate internal standard.
D.C.A. Neville, D.S. Alonzi, T. D. Butters (2012) J Chromatogr A. 13;1233:66-70.

Non-specific accumulation of glycosphingolipids in GNE myopath
K. A. Patzel, T. Yardeni, E. Le Poëc-Celic, D. S. Alonzi, N. V. Kukushkin, Y. Blériot, R. A. Dwek, W. A Gahl, M. Huizing, T. D. Butters.
Submitted to Journal of Inherited Metabolic Disease

Iminosugars as Antiviral Compounds

Combination of -glucosidase inhibitor and ribavirin for the treatment of dengue virus infection in vitro and in vivo.
J. Chang, W. Schul, T.D. Butters, A. Yip, B. Liu, A. Goh, S.B. Lakshminarayana, D.S. Alonzi, G. Reinkensmeier, X. Pan, X. Qu, J.M. Weidner, L. Wang, W. Yu, N. Borune, M.A. Kinch, J.E. Rayahin, R. Moriarty, X. Xu, P.Y. Shi, J.T. Guo and T.M. Block (2011) Antiviral Res., 89, 26-34.

Inhibitors of endoplasmic reticulum alpha-glucosidases potently suppress hepatitis C virus virion assembly and release.
X. Qu, X. Pan, J. Weidner, W. Yu, D.S. Alonzi, X. Xu, T.D. Butters, T. Block, J.T. Guo and J. Chang (2011) Antimicrobial Agents and Chemotherapy, 55, 1036-1044.

An iminosugar with potent inhibition of dengue virus infection in vivo.
S. T. Perry, M. D. Buck, E.M. Plummer, R.A. Penmasta, H. Batra, E.J. Stavale, K.L.Warfield, R.A. Dwek, T.D. Butters, D.S. Alonzi, S.M. Lada, K. King, B. Klose , U. Ramstedt, S. Shresta.
Antiviral Res. 2013 Jan 31;98(1):35-43

A Novel Iminosugar UV-12 with Activity against the Diverse Viruses Influenza and Dengue (Novel Iminosugar Antiviral for Influenza and Dengue).
K. L.Warfield, E. Plummer, D. S. Alonzi, G. W. Wolfe, A. Sampath, T. Nguyen, T. D. Butters, S. G. Enterlein, E. J. Stavale, S. Shresta, U. Ramstedt. (2015)
Viruses. May 13;7(5):2404-27.

Inhibition of endoplasmic reticulum glucosidases is required for in vitro and in vivo dengue antiviral activity by the iminosugar UV-4.
K. L.Warfield, E. M. Plummer, A. C. Sayce, D. S. Alonzi, W. Tang, B. E. Tyrrell, M. L. Hill, A. T. Caputo, S.S. Killingbeck, P. R. Beatty, E. Harris, R. Iwaki, K. Kinami, D. Ide, J. L. Kiappes, A. Kato, M. D. Buck, K. King, W. Eddy, Khaliq, A. Sampath, A. M. Treston, R. A. Dwek, S. G. Enterlein, J. L. Miller, N. Zitzmann, U. Ramstedt, S. Shresta. (2016)
Antiviral Res. Mar 2. pii: S0166-3542(16)30121-8

Iminosugars Inhibit Dengue Virus Production via Inhibition of ER Alpha-Glucosidases-Not Glycolipid Processing Enzymes.
A. C. Sayce, D. S. Alonzi, S. S. Killingbeck, B. E. Tyrrell, M. L. Hill, A. T. Caputo, R. Iwaki, K. Kinami, D. Ide, J. L. Kiappes, P. R. Beatty, A. Kato, E. Harris, R. A. Dwek, J. L. Miller, N. Zitzmann. (2016)
PLoS Negl Trop Dis. Mar 14;10(3)