Cairo, Christopher W. - University of Alberta

个人简介

BSc, State University of New York - Albany PhD, University of Wisconsin - Madison

研究领域

Research In the Lab Cell surface receptors mediate the transfer of information between cells and their environment. As a result, receptors play vital roles in all aspects of cell biology including development, immune response, homeostasis, and pharmacology. Although many receptor systems have been intensely studied, fundamental questions about their molecular function remain unanswered. Research in our group uses chemical biology to improve our mechanistic understanding of membrane biology. Specific areas of research include: Membrane Glycobiology Glycolipids are a critical structural feature of the plasma membrane. In addition to biosynthetic pathways, glycolipids content is regulated by glycosyl hydrolases at the membrane. Our group has been investigating the role of the membrane-associated neuraminidase (NEU3). Using a recombinant form of the protein, we have modeled the active site of the protein, and are working to develop specific inhibitors (Albohy, 2010). Projects in the lab continue to examine inhibition, substrate specificity, and biological function of the human neuraminidase family (Zou, 2010). Related projects are testing the role of glycosylation in the function of integrin receptors. Lipid and glycoprotein labeling strategies Chemists are uniquely qualified to develop new probes for biomolecular systems. We are applying new chemical methods to label specific receptors in live cells. Labeling strategies we are currently developing involve targeting membrane lipids (Sandbhor, 2009), glycoproteins (Loka, 2010a), surfaces (Loka, 2010b), and enzymes(Key, 2011). Synthetic Lipid Probes Membrane lipids are not only structural components of the bilayer, but also serve a role as signaling molecules. Using chemical synthesis, we are developing modified lipids which can be used to detect the location and chemical modification of sphingolipids and glycolipids (Sandbhor, 2009). Ongoing work is aimed at using these tools to probe membranes of live cells using fluorescence microscopy. Phosphatase inhibitors Phosphorylation is a prevalent post-translational modification in human cells. Phosphorylation is carried out by kinases, and removed by phosphatase enzymes - forming a regulatory cycle. Our group is developing chemical strategies to inhibit and specifically label phosphatase enzymes. Current targets include the receptor-like tyrosine phosphatase, CD45 (Tulsi, 2010). Membrane Biophysics Insight into biophysical mechanisms requires quantitative methods for observing biomolecules. We use observations of receptor motion (lateral mobility) in the plasma membrane as a tool to visualize biochemical events(Cairo, 2010). When appropriately labeled, the trajectories of single receptors can be observed and used to understand the types of interactions the receptor engages in. This methodology is highly dependent on effective labeling strategies - and can allow the visualization of nanoscale organization in the membrane. We have recently developed a new analytical method to identify the size of receptor clusters in the membrane using SPT (Rajani, 2011).

近期论文

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Leney, A.C.; Darestani, R.R.; Li, J.; Nikjah, S.; Kitova, E.N.; Zou, C.; Cairo, C.W.; Xiong, Z.J.; Prive, G.G.; Klassen, J.S.*, "Picodiscs for facile protein-glycolipid interaction analysis," Analytical Chemistry, 2015, in press. [epub Mar 24, 2015; DOI] Yang, G.-Y.; Li, C.; Fischer, M.; Cairo, C.W.; Feng, Y.; Withers, S.G.*, "A FRET PRove for Cell-Based Imaging of Gangliosiode-Processing Enzyme Activity and High-Throughput Screening," Angew. Chem., 2015, in press. [epub Mar 10, 2015; DOI] [Editor selected "Hot Paper"] Albohy, A.; Richards, M.R.; Cairo, C.W.*, "Mapping substrate interactions of the human membrane-associated neuraminidase, NEU3, using STD NMR," Glycobiology, 2014, in press. [epub Oct 6, 2014; DOI] Smutova, V.; Albohy, A.; Xuefang, P.; Korchaqina, E.; Miyagi, T.; Bovin, N.; Cairo, C.W.; Pshezhetsky, A.*, “Structural basis for substrate specificity of mammalian neuraminidases,” PLoS ONE, 2014, 9(9), e106320 [epub Sep 15, 2014; link; OA Link] Silvestri, I.; Testa, F.; Zappasodi, R.; Cairo, C.W.; Zhang, Y.; Lupo, B.; Galli, R.; Di Nicola, M.; Venerando, B.V.; Tringali, C.*, "Sialidase NEU4 is involved in glioblastoma stem cell survival," Cell Death & Disease, 2014, 5, e1381 [epub Aug 22, 2014; OA link] [highlighted in Express News, CTV Edmonton, and the Edmonton Journal] "Conformational analysis of peramivir reveals critical differences between free and enzyme-bound states," M.R. Richards, M.G. Brant, M. Boulanger, C.W. Cairo, and J.W. Wulff*, MedChemComm, 2014, 5. 1483-1488. [epub Jun 19, 2014; OA link; Inside front cover] "Practical labeling methodology for choline-derived lipids and applications in live cell fluorescence imaging," C. Li, J.A. Key, F. Jia, A. Dandapat, S. Hur, and C.W. Cairo*, Photochemistry & Photobiology, 2014, 90(3), 686-695. [epub Jan 3, 2014; DOI] [Journal Cover and Featured on journal webpage]Journal Cover for the May/June issue of Photochemistry & Photobiology, ref 27 "Mycobacterial phenolic glycolipids with a simplified lipid aglycone modulate cytokine levels through Toll-like receptor 2," H.R.H. Elsaidi, D.R. Barreda, C.W. Cairo, and T.L. Lowary*, ChemBioChem, 2013, 14(16), 2153-2159. [epub Oct 2, 2013; DOI] "alpha-Bromophosphonate analogs of glucose-6-phosphate are inhibitors of glucose-6-phosphatase," A. M. Downey and C.W. Cairo* , Carbohydrate Research, 2013, 381, 123-132. [epub Aug 10, 2013; OA link] "Interlaboratory study on differential analysis of protein glycosylation by mass spectrometry: the ABRF Glycoprotein Research Multi-institutional Study" N. Leymarie, et al. (67 authors incl. UofA contributors: C.W. Cairo , R. Daneshfar, B. Reiz, R. Whittal, and C. Zou), Molecular & Cellular Proteomics, 2012, 12, 2935-2951. [epub June 13, 2013; DOI; OA link] "Glycoform remodeling generates a synthetic T cell phenotype," C. Zou, R.S. Loka, Y. Zhang, and C.W. Cairo*, Bioconjugate Chemistry, 2013, 24(6), 907-914. [epub June 6, 2013; DOI] "Identification of Selective Nanomolar Inhibitors of the Human Neuraminidase, NEU4," A. Albohy, Y. Zhang, V. Smutova, A.V. Pshezhetsky, and C.W. Cairo*, ACS Medicinal Chemistry Letters, 2013, 4(6), 532-537. [epub May 7, 2013; DOI; OA link] [highlighted by the Faculty of Science] "Positive Regulation of Insulin Signaling by Neuraminidase 1," L. Dridi, V. Seyrantepe, A. Fougerat, X. Pan, E. Bonneil, P. Thibault, A. Moreau, G.A. Mitchell, N. Heveker, C.W. Cairo, T. Issad, A. Hinek, and A.V. Pshezhetsky*, Diabetes, 2013, 62(7), 2338-2346. [epub Mar 21, 2013; DOI; OA link] "Identification of selective inhibitors of human sialidase isoenzymes using C4, C7-modified-2-deoxy-2,3-didehydro-N-acetylneruaminic acid (DANA) analogs," Y. Zhang, A. Albohy, V. Smutova, A.V. Pshezhetsky, and C.W. Cairo*, Journal of Medicinal Chemistry, 56(7), 2948-2958 [epub Mar 26, 2013; DOI] "Protein-glycosphingolipid interactions revealed using catch-and-release mass spectrometry," Y. Zhang, L. Liu, R. Daneshfar, E.N. Kitova, C. Li, F. Jia, C.W. Cairo, and J.S. Klassen*, Analytical Chemistry, 2012, 84(18), 7618-7621. [epub Aug 24, 2012; DOI] "Detection of cellular sialic acid content using nitrobenzoxadiazole carbonyl-reactive chromophores," J.A. Key, C. Li, and C.W. Cairo*, Bioconjugate Chemistry, 2012, 23(3), 363-371. [epub Jan 30, 2012; DOI] "Substituted benzoxadiazoles as fluorogenic probes: A computational study of absorption and fluorescence," A. Brown*, T.Y. Ngai, M. Barnes, J.A. Key, and C.W. Cairo, Journal of Physical Chemistry A, 2012, 116(1), 46-54. [epub Dec 2, 2011; DOI] "Substrate recognition of the membrane-associated sialidase NEU3 requires a hydrophobic aglycone," M. Sandbhor, N. Soya, A. Albohy, R.B. Zheng, J. Cartmell, D.R. Bundle, J.S. Klassen, and C.W. Cairo*, Biochemistry, 2011, 50(32), 6753-6762. [epub Jun 15, 2011; DOI] "Selectivity of a new class of oseltamivir analogs for viral neuraminidase over human neuraminidase enzymes," A. Albohy, S. Mohan, R.B. Zheng, B.M. Pinto, and C.W. Cairo*, Bioorganic and Medicinal Chemistry, 2011, 19(9), 2817-2822. [accepted Mar 18, 2011; epub Mar 23, 2011; DOI]. "Analysis of molecular diffusion by first-passage time variance identifies the size of confinement zones," V. Rajani, G. Carrero, D.E. Golan, G. de Vries*, and C.W. Cairo*, Biophysical Journal, 2011, 100(6), 1463-1472. [accepted Jan 28, 2011; epub Mar 17, 2011; DOI; OA link].