The University of Western Australia
Dr Keith Stubbs
ARC Australian Postdoctoral Fellow
Contact details
| Address | Chemistry The University of Western Australia (M310) 35 Stirling Highway CRAWLEY WA 6009 Australia |
|---|---|
| Phone | 6488 2725 (office) / 6488 4479 (lab) |
| Fax | 6488 1005 |
| keith.stubbs@uwa.edu.au |
Location
Room 414, Molecular and Chemical Sciences 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 now holds an ARC Research 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.
Publications
Book Chapters
Keith A. Stubbs, David J. Vocadlo, Functional proteomic profiling of glycan processing enzymes. Methods in Enzymology, 2006, 415, 253.
Keith A. Stubbs, Robert V. Stick, Contribution for Electronic Encyclopedia of Reagents for Organic Synthesis; Silver Trifluoromethanesulfonate, Wiley Interscience, London, 2004.
Keith A. Stubbs, Robert V. Stick, Contribution for Electronic Encyclopedia of Reagents for Organic Synthesis; Iodine Monochloride, Wiley Interscience, London, 2004.
Journal articles
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.
Stubbs, K.A.*, and Vocadlo, D.J. Affinity-based Proteomics Probes; Tools for studying Carbohydrate-processing Enzymes. Australian Journal of Chemistry, 2009, 62, 521.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Stick, R.V., Stubbs, K.A. From glycoside hydrolases to thioglycoligases: the synthesis of thioglycosides. Tetrahedron:Asymmetry, 2005, 16, 321.
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.
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.
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.
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
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.
Keith A. Stubbs, David J. Vocadlo, Functional proteomic profiling of glycan processing enzymes. Methods in Enzymology, 2006, 415, 253.
Keith A. Stubbs, Robert V. Stick, Contribution for Electronic Encyclopedia of Reagents for Organic Synthesis; Silver Trifluoromethanesulfonate, Wiley Interscience, London, 2004.
Keith A. Stubbs, Robert V. Stick, Contribution for Electronic Encyclopedia of Reagents for Organic Synthesis; Iodine Monochloride, Wiley Interscience, London, 2004.
Journal articles
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.
Stubbs, K.A.*, and Vocadlo, D.J. Affinity-based Proteomics Probes; Tools for studying Carbohydrate-processing Enzymes. Australian Journal of Chemistry, 2009, 62, 521.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Stick, R.V., Stubbs, K.A. From glycoside hydrolases to thioglycoligases: the synthesis of thioglycosides. Tetrahedron:Asymmetry, 2005, 16, 321.
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.
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.
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.
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
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 Discovery Grant
UWA Research Development Award
UWA Research Collaboration Award
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
Australian Society of Biochemistry and Molecular Biology
Canadian Society of Biochemistry, Molecular and Cellular Biology
Honours and awards
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.
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., 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).
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
CHEM2211 Synthetic and Materials 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
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
