The University of Western Australia

Assoc/Prof Keith Stubbs

Research Associate Professor
School of Chemistry and Biochemistry

Contact details

Address

School of Chemistry and Biochemistry
The University of Western Australia (M313)
35 Stirling Highway
CRAWLEY WA 6009
Australia

Phone

6488 2725 (office) / 6488 4479 (lab)

Fax

6488 1005

Email

keith.stubbs@uwa.edu.au

Location

Room 414, Bayliss Building, Crawley campus

Biography

Dr Keith Stubbs completed his undergraduate and PhD studies at UWA, followed by a two year post-doctoral position at Simon Fraser University in Vancouver, Canada. He currently holds an ARC Australian Post-Doctoral Fellowship but has been awarded an ARC Future Fellowship to further his research.

Key research

Keywords: Carbohydrate chemistry, Glycobiology, Enzymology, Enzyme Inhibitors, Proteomics

Carbohydrates are present in every living system from prokaryotes to eukaryotes and traditionally, have been known for their role in the structural integrity of plants and as energy sources. Recently, however, carbohydrates have been shown to be involved in a variety of fundamental biological processes such as protein folding and trafficking, as well as cellular signaling and recognition. As we gain greater understanding into the roles that carbohydrates play at the cellular level, scientists are faced with new challenges. On the chemistry side, unique carbohydrate-based tools need to be developed and in turn used to investigate the specific roles that a single mono- or polysaccharide plays in the dynamics of the cell in order to keep up with the biochemical discovery of new glycan structures and the enzymes that regulate them. My research aims are to address the development of such tools.

For students, if you have any interests in these areas please feel free to contact me.

Publications

Book Chapters

(3) Keith A. Stubbs, David J. Vocadlo, Functional proteomic profiling of glycan processing enzymes. Methods in Enzymology, 2006, 415, 253.

(2) Keith A. Stubbs, Robert V. Stick, Contribution for Electronic Encyclopedia of Reagents for Organic Synthesis; Silver Trifluoromethanesulfonate, Wiley Interscience, London, 2004.

(1) Keith A. Stubbs, Robert V. Stick, Contribution for Electronic Encyclopedia of Reagents for Organic Synthesis; Iodine Monochloride, Wiley Interscience, London, 2004.

Journal articles

(40) Yeung S.Y., Kampmann, S. Stubbs, K.A., Skelton, B.J., Kaskow, B.J., Abraham, L. and Stewart, S.G. Novel Thalidomide Analogues with Potent NFKB and TNF expression Inhibition. MedChemComm, 2011, 2, 1073.

(39) Clemons, T.D., Evans, C.W. Zdyrko, B., Luzinov, I., Fitzgerald, M., Dunlop, S.A., Harvey, A.R., Iyer, K.S. and Stubbs, K.A.* A general Multifunctional nanoadditives for thermodynamic and kinetic stabilization of enzymes. Nanoscale, 2011, 3, 4085.

(38) Paterson, S.M., Clark, J., Stubbs, K.A.*, Chirila, T.V., and Baker, M.V. Carbohydrate-based crosslinking agents: Potential uses in hydrogels. The Journal of Polymer Science Part A: Polymer Chemistry, 2011, 49, 4312.

(37) Moréra, S., Vigouroux, A., and Stubbs, K.A.* A potential fortuitous binding of inhibitors of inverting family GH9 beta-glycosidase derived from isofagomine. Organic and Biomolecular Chemistry, 2011, 9, 5945.

(36) Martin, A.D., Boulos, R.A., Stubbs, K.A., Raston, C.L. Phosphonated calix[4]arene-based amphiphiles as scaffolds for fluorescent nano-fibres. Chemical Communications, 2011, 47, 7329.

(35) Gandy, M.N., Debowski, A.W., and Stubbs, K.A.* A general method for affinity-based proteomic profiling of exo-alpha-glycosidases. Chemical Communications, 2011, 47, 5037.

(34) Bacik, J.P., Whitworth, G.E., Stubbs, K.A., Yadav, A.K., Martin, D.R., Bailey-Elkin, B.A., Vocadlo, D.J., and Mark, B.L. Molecular Basis of 1,6-Anhydro Bond Cleavage and Phosphoryl Transfer by Pseudomonas aeruginosa 1,6-Anhydro-N-acetylmuramic Acid Kinase. Journal of Biological Chemistry, 2011, 286, 12283.

(33) He, Y., Bubb, A.K., Stubbs, K.A., Gloster, T.M., and Davies, G.J. Inhibition of bacterial O-GlcNAcase by lactone and lactam derivatives: structural, kinetic and thermodynamic analyses. Amino Acids. 2011, 40, 829.

(32) Gandy, M.N., Piggott, M.J. and Stubbs, K.A.*, An Expeditious Synthesis of Iminosugars. The Australian Journal of Chemistry, 2010, 63, 1409.

(31) Tognetti, V.B., Van Aken, O., Morreel, K., Vandenbroucke, K., van de Cotte, B., De Clercq, I., Chiwocha, S., Fenske, R., Prinsen, E., Boerjan, W., Gentye, B., Stubbs, K.A., Inze, D., and van Breusegem, F., Perturbation of indole-3-butyric acid homeostasis by the UDP-glucosyltransferase UGT74E2 modulates Arabidopsis architecture and water stress tolerance. The Plant Cell, 2010, 22, 2660.

(30) Macauley, M.S., He, Y., Gloster, T.G, Stubbs, K.A., Davies, G.J., and Vocadlo, D.J., Inhibition of OGA using a Potent and Cell Permeable Inhibitor of O-GlcNAcase does not Induce Insulin Resistance in 3T3-L1 Adipocytes. Chemistry and Biology. 2010, 17, 937.

(29) Stewart S.G., Braun C.J., Polomska M.E., Karimi M., Abraham L.J., Stubbs K.A., Efforts toward elucidating Thalidomide's molecular target: an expedient synthesis of the first Thalidomide biotin analogue. Organic and Biomolecular Chemistry, 2010, 8, 4059.

(28) Goddard-Borger, E.D., and Stubbs, K.A.*, An Improved route to PUGNAc and its Galacto-configured Congener. The Journal of Organic Chemistry, 2010, 61, 3931.

(27) Gunasekara, S. Vrielink, A. and Stubbs, K.A.*, Preliminary Studies into the Inhibition of the Cholesterol alpha-glucosyltransferase from Helicobacter pylori Using Azasugars. Carbohydrate Research, 2010, 345, 960.

(26) He Y., Macauley M.S., Stubbs K.A., Vocadlo D.J., Davies G.J. Visualizing the reaction coordinate of an O-GlcNAc hydrolase. Journal of the American Chemical Society, 2010, 132, 1807.

(25) Pluvinage, B., Ghinet, M.G., Brzezinski, R., Boraston, A.B., and Stubbs, K.A.* Inhibition of the exo-beta-D-glucosaminidase CsxA by a glucosamine-configured castanospermine and an amino-australine analogue. Organic and Biomolecular Chemistry, 2009, 7, 4169.

(24) Stubbs, K.A.*, and Vocadlo, D.J. Affinity-based Proteomics Probes; Tools for studying Carbohydrate-processing Enzymes. Australian Journal of Chemistry, 2009, 62, 521.

(23) Balcewich, M., Stubbs, K.A., He, Y., James, T., Davies, G.J. Vocadlo D.J., and Mark B.L. Insight into a strategy for attenuating AmpC-mediated beta-lactam resistance: structural basis for selective inhibition of the glycoside hydrolase NagZ. Protein Science, 2009, 18, 1541.

(22) Asgarali, A., Stubbs, K.A., Oliver, A., Vocadlo D.J., and Mark B.L. Inactivation of the glycoside hydrolase NagZ attenuates anti-pseudomonal beta-lactam resistance in Pseudomonas aeruginosa. Antimicrobial Agents and Chemotherapy, 2009, 53, 2274.

(21) Stubbs, K.A.*, Macauley, M.S., Vocadlo, D.J. A selective inhibitor of human lysosomal beta-hexosaminidases: Gal-PUGNAc modulates levels of the ganglioside GM2 in neuroblastoma cells. Submitted to Angewandte Chemie International Edition, 2009, 48, 1300.

(20) Scaffidi A., Stubbs K.A.*, Vocadlo D.J., Stick R.V. The Synthesis and Biological Evaluation of Some Carbocyclic Analogues of PUGNAc. Carbohydrate Research, 2008, 343, 2744.

(19) Yuzwa, S.A., Macauley M.S., Heinonen, J.E., Shan, X., Dennis R.J., Whitworth G.E., Stubbs K.A., McEachern E.J., Davies G.J., Vocadlo D.J. A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo. Nature Chemical Biology, 2008, 4, 483.

(18) Ficko-Blean E., Stubbs K.A., Berg O., Vocadlo D.J., Boraston A.B. Structural and mechanistic insight into the basis of mucopolysaccharidosis IIIB. Proceedings of the National Academy of Sciences USA, 2008, 105, 6560.

(17) Choudbar, N., Bhat, R. G., Stubbs, K.A., Yuzwa, S, Pinto, B.M. Synthesis of 2-Amido, 2-Amino, and 2-Azido derivatives of the nitrogen analogue of the naturally occurring glycosidase inhibitor salacinol and their inhibitory activities against O-GlcNAcase and NagZ enzymes. Carbohydrate Research, 2008, 343, 1766.

(16) Stubbs K.A., Scaffidi A., Debowski A.W., Mark B.L., Stick R.V., Vocadlo D.J. Synthesis and use of mechanism-based protein-profiling probes for retaining b-D-glucosaminidases facilitate identification of Pseudomonas aeruginosa NagZ. Journal of the American Chemical Society, 2008, 130, 327.

(15) Scaffidi A., Stubbs K.A.*, Dennis R.J., Taylor E.J., Davies G.J., Vocadlo D.J., Stick R.V. A 1-Acetamido Derivative of 6-Epivalienamine: An Inhibitor of a Diverse Group of beta-N-acetylglucosaminidases. Organic and Biomolecular Chemistry, 2007, 5, 3013.

(14) Stubbs K.A., Balcewich M., Mark B.L., Vocadlo D.J. Small molecule inhibitors of a glycoside hydrolase attenuate inducible AmpC mediated beta-lactam resistance. Journal of Biological Chemistry, 2007, 282, 21382.

(13) Scaffidi, A., Stick, R.V., Stubbs, K.A. Synthesis of Some Glycosylated Derivatives of 2-Deoxy-2-fluoro-beta-laminaribiosyl Fluoride: Another Success for Glycosynthases. Australian Journal of Chemistry, 2007, 60, 83.

(12) Whitworth G.E., Macauley M.S., Stubbs K.A., Dennis R.J., Davies G.J., Greig I.R., Vocadlo D.J. Analysis of PUGNAc and NAG-thiazoline as Transition State Analogues for Human O-GlcNAcase: Mechanistic and Structural Insights into Inhibitor Selectivity and Transition State Poise. Journal of the American Chemical Society, 2007, 129, 635.

(11) Dennis R.J., Taylor E.J., Macauley M.S., Stubbs K.A., Turkenburg J.P., Hart S.J., Black G.N., Vocadlo D.J., Davies G.J. Structure and mechanism of a bacterial beta-glucosaminidase having O-GlcNAcase activity. Nature Structural and Molecular Biology, 2006, 13, 365.

(10) Stubbs, K.A., Zhang N., Vocadlo, D.J. A rapid and divergent synthesis of 2-acyl derivatives of PUGNAc. Potent and selective inhibitors of O-GlcNAcase. Organic and Biomolecular Chemistry, 2006, 4, 839.

(9) Stubbs, K.A., Macauley, M.A., Vocadlo, D.J. A Simple and Concise Synthesis of Aryl 2-acetamido-2-deoxy-1-thio-beta-D-glucopyranosides. Carbohydrate Research, 2006, 341, 1764.

(8) Cetinbas, N., Macauley, M.A., Stubbs, K.A., Drapala, R., Vocadlo D.J. Identification of Asp174 and Asp175 as the key catalytic residues of human O-GlcNAcase by functional analysis of site-directed mutants. Biochemistry, 2006, 45, 3835.

(7) Macauley, M.A., Stubbs, K.A., Vocadlo, D.J. O-GlcNAcase catalyzes cleaveage of thioglycosides without general acid catalysis. Journal of the American Chemical Society, 2005, 127, 17202.

(6) Stick, R.V., Stubbs, K.A. The synthesis of a new class of potential inhibitor for glycoside hydrolases. Journal of Carbohydrate Chemistry, 2005, 24, 529.

(5) Stick, R.V., Stubbs, K.A. From glycoside hydrolases to thioglycoligases: the synthesis of thioglycosides. Tetrahedron:Asymmetry, 2005, 16, 321.

(4) Stick, R.V., Stubbs, K.A., Watts, A.G. Modifying the regioselectivity of glycosynthase reactions through the rational design of modified acceptors. Australian Journal of Chemistry, 2004, 57, 779.

(3) Stick, R.V., Stubbs, K.A., Watts, A.G. The fluorination (at C5) of some derivatives of D-glucose. Australian Journal of Chemistry, 2004, 57, 345.

(2) Stick, R.V., Stubbs, K.A., Tilbrook, D.M.G., Watts, A.G. A new catalyst for the reductive elimination of acylated glycosyl bromides to form glycals. Australian Journal of Chemistry, 2002, 55, 83.

(1) Stick, R.V., Stubbs, K.A., Tilbrook, D.M.G. An improved synthesis of (R)-2,3-dihydroxypropyl 5-deoxy-5-dimethylarsinyl-beta-D-riboside, a common marine arsenical. Australian Journal of Chemistry, 2001, 54, 181.

Conference papers

(3) Gandy, M.N., Debowski, A.W., and Stubbs, K.A.* The development of tools for the affinity-based proteomic profiling of exo-alpha-glycosidase activity. Glycobiology, 2011, 21, 1517.

(2) Vocadlo, D., Yuzwa, S., Macauley, M.S., Henioen, J.E., Shan, X., Whitworth, G.E., Stubbs, K.A., Davies, G.J., Dennis, R., Modulators of intracellular glycosylation limit microtubule-associated protein tau phosphorylation in vivo. Biochemistry and Cell Biology-Biochimie et Biologie Cellulaire, 2010, 88, 412.

(1) Whitworth, G.E., Stubbs, K.A., Macauley, M.S., Dennis, R.J., Davies, G.J., Greig, I.R., and Vocadlo, D.J. Analysis of PUGNAc and NAG-thiazoline as Transition State Analogues for Human O-GlcNAcase: Mechanistic and Structural Insights into Inhibitor Selectivity and Transition State Poise. Biochemistry and Cell Biology-Biochimie et Biologie Cellulaire, 2008, 86, 201.

Funding received

ARC Future Fellowship
ARC Discovery Grants
National Health and Medical Research Council Project Grant
ARC LIEF Grants
Perpetual Funding
UWA Research Development Award
UWA Research Collaboration Award

Memberships

Royal Australian Chemistry Institute
Australian Society of Biochemistry and Molecular Biology
Canadian Society of Biochemistry, Molecular and Cellular Biology
Society for Glycobiology

Honours and awards

2011 Hoffmann-La Roche/Groupe Français des Glucides Travel Award

2008-2010 Michael Smith Foundation of Health Research Post-Doctoral Fellowship - Awarded to one of the best applicants in the Biomedical Sciences Section.

2007 Merck Frosst Biology Research Day Presentation Award - For the best presentation at Merck Frosst Biology Research Day

2007 Canadian Society of Biochemistry, Molecular and Cellular Biology - Awarded for being the best Post-Doctoral Fellow at the CSBMCB Symposium Meeting, 2007.

2007 Merck Frosst Travel Award – Awarded to give talks at universities in the eastern provinces of Canada.

2004 Australia New Zealand Glycoscience Group Travel Award - Awarded to attend the International Carbohydrate Symposium, Glasgow, Scotland.

Patents

Vocadlo, D.J, McEachern, E.J, Stubbs, K. SELECTIVE GLYCOSIDASE INHIBITORS AND USES THEREOF. PCT Intl. Appl., WO 2010012106, (2010).

Vocadlo, D., McEachern, E., Whitworth, G., Macauley, M., Heinonen, J., Stubbs, K., Li, T.-S. SELECTIVE GLYCOSIDASE INHIBITORS AND USES THEREOF. PCT Intl. Appl., WO 2008025170, (2008).

Vocadlo, D. and Stubbs, K. NAGZ INHIBITORS ATTENUATE INDUCTION OF AMPC BETA-LACTAMASE, Provisional Patent, (2007) USPTO Application No. 60892426.

Vocadlo, D., Whitworth, G., Macauley, M., Stubbs, K. SELECTIVE GLYCOSIDASE INHIBITORS, METHODS OF MAKING INHIBITORS, AND USES THEREOF. PCT Intl. Appl., WO 2006092049, (2006).

Teaching

CHEM3302 Structure Determination in Chemistry

Current projects

Collaborators

Dr David Vocadlo, SFU
Prof Gideon Davies, University of York
Dr Brian Mark, University of Manitoba
Dr. Alisdair Boraston, University of Victoria
Dr Sean Sweeney, University of York
Dr Yves Bleriot, Universite Pierre et Marie Curie
Prof Barry Marshall, Univeristy of Western Australia
A/Prof Mohammed Benghezal, Univeristy of Western Australia
Prof Alice Vrielink, Univeristy of Western Australia
A/Prof Charlene Kahler, Univeristy of Western Australia

Research profile

Research profile and publications