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Warren G Lewis, Ph.D.

Selected Publications

Biochemical, molecular, and microbial studies of bacterial vaginosis

  1. Lewis, W.G.; Robinson, L.S.; Perry, J.C.; Bick, J.L.; Peipert, J.F.; Allsworth, J.E.; Lewis, A.L. Hydrolysis of the secreted sialoglycoprotein Immunoglobulin A (IgA) in ex vivo and biochemical models of bacterial vaginosis.  J. Biol. Chem. 2012; 287(3): 2079-89. PMID: 22134918.

  2. Lewis, W.G.; Robinson, L.S.; Gilbert, N.M.; Perry, J.C.; Lewis, A.L. Degradation, foraging and depletion of mucus sialoglycans by the vagina-adapted Actinobacterium Gardnerella vaginalis. J. Biol. Chem. 2013; 288(17), 12067-79. PMID: 23479734.

  3. Robinson L.S., Schwebke J., Lewis W.G., and Lewis A.L. Identification and characterization of NanH2 and NanH3, the enzymes responsible for sialidase activity in Gardnerella vaginalis. 2019 J Biol Chem pii: jbc.RA118.006221. doi: 10.1074/jbc.RA118.006221. PMID: 30723162.

  4. Agarwal KA, Robinson LS, Aggarwal S, Lynne Foster LR, Hernandez-Leyva A, Lin H, Tortelli BA, O’Brien VP, Miller L, Kau AL, Reno H, Gilbert NM, Lewis WG*, Lewis AL*. Glycan cross-feeding supports mutualism between Fusobacterium and the vaginal microbiota. PLoS Biology, 2020 Aug 25;18(8):e3000788.doi: 10.1371/journal.pbio.3000788. eCollection 2020 Aug. PMID: 32841232 PMCID: PMC7447053 * Co-Corresponding authors

Fuzzy Gardnerella.png

Degradation of protein and carbohydrate components of mucus related to microbial interactions with the gastrointestinal tract.

  1. Robinson L.S., Lewis W.G., Lewis A.L. The Sialylate O-acetylesterase EstA from Gut Bacteroides Species Enables Sialidase-Mediated Cross-species Foraging of 9-O-acetylated Sialoglycans. J Biol Chem. 2017 pii: jbc.M116.769232. doi: 10.1074/jbc.M116.769232. PMID: 28526748.

  2. Luo Q., Kumar P., Vickers T.J., Sheikh A., Lewis W.G., Rasko D.A., Sistrunk J., Fleckenstein J.M. Enterotoxigenic Escherichia coli secretes a highly conserved mucin-degrading metalloprotease to effectively engage intestinal epithelial cells. Infect Immun. 2014 Feb;82(2):509-21. doi: 10.1128/IAI.01106-13. PubMed PMID: 24478067

  3. Kumar P., Luo Q., Vickers T.J., Sheikh A., Lewis W.G., Fleckenstein J.M. EatA, an immunogenic protective antigen of enterotoxigenic Escherichia coli, degrades intestinal mucin. Infect Immun. 2014; 82(2):500-8. doi: 10.1128/IAI.01078-13. PMID: 24478066

SEM mouse vag.png
Fig 4 EstA kinetics- 9-OAc preferred.png

Glycan biosynthesis & its functions in pathogens.

To understand how bacteria make surface carbohydrates, and the functional consequences of the saccharide coating of pathogen cell surfaces, I apply biochemical and cellular assays to understand the origins & biological consequences of glycan decoration in bacteria, nematodes and other parasites.

Vibrio.png

  1. Cai CW, O’Shea A, Eickhoff CS, Guo H, Lewis WG, Beverley SM and Hoft DF. Use of Leishmania major parasites expressing a recombinant Trypanosoma cruzi antigen as live vaccines against Chagas disease. Front. Microbiol. 13:1059115 2022. doi: 10.3389/fmicb.2022.1059115

  2. Lubin, J.B.; Lewis, W.G.; Gilbert, N.; Weimer, C.M.; Almagro-Moreno, S.; Boyd, E.F.; Lewis, A.L. Host-like carbohydrates promote bloodstream survival of Vibrio vulnificus in vivo. Infect Immun. 2015; 83(8): 3126-36. PMID: 26015477

  3. Tyagi, R.; Rosa, B.; Lewis, W.G.; Mitreva, M. Pan-phylum Comparison of Nematode Metabolic Potential PLoS Neglected Tropical Diseases. 2015; 9(5):e0003788 PMID: 26000881

  4. Kline, K.A.; Schwartz, D.J.; Lewis, W.G.; Hultgren, S.J.; Lewis, A.L. 2011. Immune Activation and Suppression by Group B Streptococcus in a Murine Model of Urinary Tract Infection. Infect Immun. 79(9):3588-95. PMID: 21690238

Kinase Inhibitors as Chemical Probes for Biological Processes.

  • Chemical probes for biological processes mediated by serine-threonine kinases.

  • Cellular and organismal circadian rhythms are controlled by AKT-GSK3b and casein kinases of human and zebrafish, changing the circadian day by many hours.

  • Developed cellular kinase inhibitor selectivity panel of phosphorylation assays.

  • Biochemical assay development using enzyme and inhibitor conjugates.

  1. Hirota, T.; Lewis, W.G.; Liu, A.; Lee J.W.; Schultz, P.G.; Kay, S.A. A chemical biology approach reveals period shortening of the mammalian circadian clock by specific inhibition of GSK-3beta.  Proc. Nat. Acad. Sci. U S A. 2008. 105(52): 20746-51. PMID: 19104043.

  2. Hirota, T.; Lee, J.W.; Lewis, W.G.; Zhang,E.E.; Breton,G.; Liu, X.; Garcia, M.; Peters, E.C.; Etchegaray, J-P.; Traver, D.; Schultz, P.G.; Kay, S.A.  High-Throughput chemical screen identifies a novel potent modulator of cellular circadian rhythms and reveals CKIα as a clock regulatory kinase.  PLoS Biology 2010. 8(12): e1000559.    PMID: 21179498

  3. Liu, A.C.; Lewis, W.G.; Kay, S.A. Mammalian circadian signaling networks and therapeutic targets. Nat. Chem. Biol. 2007. 3: 630-639. (Review) PMID: 17876320

  4. Wodicke, L.; Lewis, W.G.; Treiber, D.

      Cellular Assay Employing Detectable Protein

            US2012045769  (A1)

            EP 2,421,989

            WO 2,010,124,157

            (Assignee: DiscoveRx, formerly Ambit Biosciences)

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