Dr. Joseph S. Lam

Our research focuses on the lipopolysaccharide component of the outer membrane of Gram-negative bacteria.

My laboratory is studying pathogenesis of lung infection in cystic fibrosis patients caused by Pseudomonas aeruginosa. The specific focuses are to understand the molecular biology of the biosynthesis of lipopolysaccharide (LPS) in the bacterium, Pseudomonas aeruginosa, the role of LPS in pathogenesis, and to investigate the use of glycoconjugates and enzymes in the LPS metabolic pathways as "targets" for developing new antimicrobials to control P. aeruginosa infections. We use cutting-edge technology and develop new methods to deal with genes and their encoded protein products associated with LPS synthesis and regulations. We routinely over-express these proteins using pET, pBAD and other systems; and purify them using FPLC. This allows us to perform various studies including mass spectrometry, x-ray crystallography, kinetics of interactions among various proteins, and importantly, development of assays that can be used for high-throughput drug screening (this last aspect is very costly and is done through a collaboration with a pharmaceutical company). My laboratory is well equipped with modern research instrumentation including a capillary electrophoresis (CE), a biosensor apparatus, BIACORE, and a FPLC/HPLC instrument for protein purification. Research in my laboratory provides a broad-based training for postdoctoral fellows, graduate students, and senior undergraduate project students in microbiology, molecular biology and biochemistry.

Refereed papers (2010-2014):

1. Penterman, J., Nguyen, D., Anderson, E.L., Staudinger, B.J., Greenberg, E.P., Lam, J.S., & Singh, P.K. 2014. Rapid Evolution of Culture-Resistant Bacteria During Adaptation to Biofilm Growth. Cell Reports (In press, accepted Oct. 30, 2013) (PMID: 24412364)
2. Islam S.T., Huszczynski S.M., Nugent, T., Gold, A.C., & Lam, J.S. 2013. Conserved-residue mutations in Wzy affect O-antigen polymerization and Wzz-mediated chain-length regulation in Pseudomonas aeruginosa PAO1. Sc. Rep. 3:3441 (doi: 10.1038/srep03441; PMID: 24309320)
3. Pires, D.P., Silva, S., Almeida, C., M. Henriques, E.M. Anderson, J.S. Lam, S. Sillankorva, & J. Azeredo. 2013. Evaluation of the ability of C. albicans to form biofilm in the presence of P. aeruginosa phage-resistant phenotypes. Biofouling. 29:1169-1180 (PMID: 24063626)
4. Islam, S.T., P.D.W. Eckford, M.L. Jones, T. Nugent, C.E. Bear, C. Vogel, and J.S. Lam. 2013. Proton-dependent gating and proton uptake by Wzx support O-antigen-subunit antiport across the bacterial inner membrane. mBio 4(5). pii: e00678-13, (doi:10.1128/mBio.00678-13) (PMID: 24023388) (Highlighted by F1000 Prime as an important paper)
5. Taylor, V.L., M.L. Udaskin, S.T. Islam, and Joseph S. Lam. 2013. The D3 bacteriophage a-polymerase-inhibitor (Iap) peptide disrupts O-antigen biosynthesis through mimicry of the chain length regulator Wzz in Pseudomonas aeruginosa. J. Bacteriol. 195: 4735-4741 (PMID: 23955007)
6. Wang S, H. Tanaka, O. Hindsgaul, J.S. Lam JS, and Brockhausen I. 2013. A convenient synthesis of GDP-D-rhamnose: the donor substrate for D-rhamnosyltransferase WbpZ from Pseudomonas aeruginosa PAO1. Bioorg Med Chem Lett. 2013 23:3491-3495. (doi: 10.1016/j.bmcl.2013.04.051) (PMID: 23664878)
7. Kocíncová, D. and J.S. Lam. 2013. A deletion in the wapB promoter in many serotypes of Pseudomonas aeruginosa accounts for the lack of a terminal glucose residue in the core oligosaccharide and resistance to killing by R3-pyocin. Mol. Microbiol. 89:464-478 (DOI: 10.1111/mmi.12289) (PMID: 23750877)
8. Islam, S.T. and J.S. Lam. 2013. Topologcial mapping methods for ?-helical bacterial membrane proteins - an update and a guide. MicrobiologyOpen 2:350-364 (doi: 10.1002/mbo3.72) (PMID: 23408725) (Highlighted by the editor as Article of the Month in June, 2013).
9. Hao, Y, J.D. King, S. Huszczynski, D. Kocíncová, J.S. Lam. 2013. Five new genes are important for common polysaccharide antigen biosynthesis in Pseudomonas aeruginosa. mBio: 4(1):e00631-12. doi:10.1128/mBio.00631-12. Open Access (PMID: 23341552)
10. Fernández, L, C. Álvarez-Ortega, I. Wiegand, J. Olivares, D. Kocíncová, J.S. Lam, J.L. Martínez, and R.E.W. Hancock. 2013 Characterization of the polymyxin B resistome of Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 57:111-119. (PMID: 23070157)
11. Islam, S.T. and J.S. Lam. 2013 Wzx flippase-mediated membrane translocation of sugar polymer precursors in bacteria. Environ. Microbiol. 15:1001-1015. doi:10.1111/j.1462-2920.2012.02890.x (PMID: 23016929)
12. McLean, R.J.C. McLean, J.S. Lam, and L.L. Graham. 2012. Training the biofilm generation - A tribute to J.W. Costerton. Mini-review submitted to J. Bacteriol. 194:6706-6711. doi: 10.1128/JB.01252-12. (PMID: 22961848)
13. Wang, W., T. Archbold, M.S. Kimber, J. Li, J.S. Lam, and M. Z. Fan. 2012. The porcine gut microbial metagenomic library for mining novel cellulases established from growing pigs fed cellulose-supplemented high-fat diets. J. Anim. Sc. 90:400-402. (doi: 10.2527/jas.53942) (PMID: 23365392)
14. Kocíncová, D., Ostler, S.L., E.M. Anderson, and J.S. Lam. 2012. Rhamnosyltransferase genes migA and wapR are regulated in a differential manner to modulate the quantities of core oligosaccharide glycoforms produced by Pseudomonas aeruginosa. J. Bacteriol. 194:4295-4300 (DOI:10.1128/JB.05741-11) (PMID: 22685285)
15. Zegans, M.E., D. Wozniak, E. Griffin, C.M. Toutain-Kidd, J.H. Hammond, Andrew Garfoot, and J.S. Lam. 2012. Pseudomonas aeruginosa exopolysaccharide Psl promotes resistance to the biofilm inhibitor polysorbate 80. Antimicrob. Agents Chemother. 56:4112-4122. (DOI:10.1128/AAC.00373-12) (PMID: 22585230)
16. Ma, L., J. Wang, S. Wang, E.M. Anderson, J.S. Lam, M.R. Parsek, and D.J. Wozniak. 2012. Synthesis of multiple Pseudomonas aeruginosa biofilm matrix exopolysaccharides is post-transcriptionally regulated. Environ. Microbiol. 14:1995-2005. (DOI: 10.1111/j.1462-2920.2012.02753.x) (PMID: 22513190)
17. Islam, S.T., R.J. Fieldhouse, E.M. Anderson, V.L. Taylor, R.A.B. Keates, R.C. Ford, and J.S. Lam. 2012. A cationic lumen channel in the Wzx flippase mediates anionic O-antigen subunit translocation in Pseudomonas aeruginosa PAO1. Mol. Microbiol. 86: 1165-1176. doi:10.1111/j.1365-2958.2012.08084.x (Highlighted by Faculty of 1000 Biology as a Must Read article) (PMID: 22554073)
18. Kocíncová, D. and J.S. Lam. 2011. Structural diversity of the core oligosaccharide domain of Pseudomonas aeruginosa lipopolysaccharide. Biochemistry (Mosc) 76:755-760 (DOI: 10.1134/S0006297911070054). (PMID: 21999536)
19. DeLucia, A.M., D.A. Six, R.E. Caughlan, P. Gee, I. Hunt, J.S. Lam, and C.R. Dean 2011. Lipopolysaccharide (LPS) inner-core phosphates are required for complete LPS synthesis and transport to the outer membrane in Pseudomonas aeruginosa PAO1. mBio 2(4):e00142-11. doi:10.1128/mBio.00142-11 (PMID: 21810964)
20. Lam, J.S., V.L. Taylor, S.T. Islam, Y. Hao, and D. Kocíncová 2011. Genetics and functional diversity of Pseudomonas aeruginosa lipopolysaccharide. Frontiers in Microbiol. 2:118 (doi: 10.3389/fmicb.2011.00118) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108286/ (PMID: 21687428) Open Acc.
21. Islam, S.T., A.C. Gold, V.L. Taylor, E.M. Anderson, R. C. Ford, and J.S. Lam. 2011. Dual conserved periplasmic loops possess essential charge characteristics that supports a catch-and-release mechanism of O-antigen polymerization by Wzy in Pseudomonas aeruginosa PAO1. J. Biol. Chem. 286: 20600-20605. (DOI 10.1074/jbc.C110.204651) (PMID: 21498511) Free Acc.
22. Kocíncová, D., Y. Hao, E. Vinogradov, and J.S. Lam. 2011. Evidence that WapB is an 1,2 glucosyltransferase of Pseudomonas aeruginosa involved in LPS outer core biosynthesis. J. Bacteriol. 193:2708-2716. (doi:10.1128/JB.00032-11) (PMID: 21441506) Free Acc.
23. Veeranagouda, Y., A.R. Cho, K.M. Cho, K. Cho, E.M. Anderson, J.S. Lam, and K. Lee. 2011. Glycosyltransferase Ssg is involved in lipo- and exo-polysaccharide biosynthesis in Pseudomonas alkylphenolia and its mutation affects cell surface-related properties. FEMS Microbiol. Lett. 315:38-45. (PMID: 21166709)
24. Islam S.T., V.L. Taylor, M. Qi†, and J.S. Lam. 2010. Membrane topology mapping of the O-antigen flippase (Wzx), polymerase (Wzy), and ligase (WaaL) from Pseudomonas aeruginosa PAO1 reveals novel domain architectures. mBio 1(3):300189-10. Doi:10.1128/mBio.00189-10. (Highlighted by Faculty of 1000 Biology, http://beta.f1000.com/5183959) (PMID: 20824106) Open Acc.
25. King, J.D., E. Vinogradov, V. Tran, and J.S. Lam. 2010. Biosynthesis of uronamide sugars in Pseudomonas aeruginosa O6 and Escherichia coli O121 O antigens. Environ. Microbiol. 12:1531-1544. (PMID: 20192967)
26. Gravelle, S.K., R.J. Barnes, J.K. Eibl, J.S. Lam, and M. Ulanova. 2010. Upregulation of integrin expression in lung adenocarcinoma cells caused by bacterial infection. Innate Immunity 16:14-26. (PMID: 19710103)
27. Lau, P.C. Y., T. Lindhout, T.J. Beveridge, J.R. Dutcher and J.S. Lam. 2009. Differential lipopolysaccharide core capping leads to quantitative and correlated modifications of mechanical and structural properties in Pseudomonas aeruginosa biofilms. J. Bacteriol. 191:6618-6631 (Highlighted in Microbe, Dec. issue, as article of the month of J. Bacteriol.). (PMID: 19717596) Free Acc.
28. King, J.D., D. Kocíncová, E.L. Westman and J.S. Lam. 2009. Lipopolysaccharide biosynthesis in Pseudomonas aeruginosa. Innate Immunity 15:261-312. (E-pub ahead of print since Aug. 24, 2009) (PMID: 19710102).
29. Pinta, E., K.A. Duda, A. Hanuszkiewicz, Z. Kaczynski, B. Lindner, W.L. Miller, H. Hyytiäinen, C. Vogel, S. Borowski, K. Kasperkiewicz, J.S. Lam, J. Radziejewska-Lebrecht, M. Skurnik, and O. Holst. 2009. Identification and role of a 6-deoxy-4-keto-hexosamine in the lipopolysaccharide outer core of Yersinia enterocolitica serotype O:3. Chemistry - A European Journal, 15:9747-9754. (PMID: 19697383)
30. Lindhout, T., P. C.Y. Lau, D. Brewer, and J.S. Lam. 2009. Truncation in the core oligosaccharide of lipopolysaccharide affected flagella-mediated motility in Pseudomonas aeruginosa PAO1 via modulation of cell surface attachment. Microbiology (UK), 155:3449-3460. (PMID: 19589832)
31. Byrd, M.S., I. Sadovskaya, E. Vinogradov, H. Lu, A. Sprinkle, S. Richardson, L. Ma, B. Ralston, M.R. Parsek, E.M. Anderson, J.S. Lam, and D. J. Wozniak. 2009. Genetic and biochemical analyses of the Pseudomonas aeruginosa Psl exopolysaccharide reveal overlapping roles for polysaccharide synthesis enzymes in Psl and LPS production. Mol. Microbiol. 73:622-638. (PMID: 19659934)
32. Westman, E.L., D.J. McNally, A. Charchoglyan, D. Brewer, R.A. Field, and Joseph S. Lam. 2009. Characterization of WbpB, WbpE, and WbpD, and reconstitution of a pathway for the biosynthesis of UDP-2,3-diacetamido-2,3-dideoxy-D-mannuronic acid in Pseudomonas aeruginosa. J. Biol. Chem. 284:11854-11862 (E pub ahead of print on Mar. 12, 2009) (PMID: 19282284) Free Acc.
33. King, J.D., K.K.H. Poon, N.A. Webb, E.M. Anderson, D.J. McNally, J.R. Brisson, P. Messner, R.M. Garavito, and Joseph S. Lam. 2009. The structural basis for catalytic function of GMD and RMD, two closely related enzymes from the GDP-D-rhamnose biosynthesis pathway. FEBS J. 276:2686-2700. (PMID: 19459932)
34. Lau, P.C.Y., J.R. Dutcher, T.J. Beveridge, and J.S. Lam. 2009. Absolute quantitation of bacterial biofilm adhesion and viscoelasticity by microbead force spectroscopy. Biophys. J. 96:2935-2948. (PMID: 19348775) Free Acc.
35. Rejzek, M., V.S. Kannathasan, C. Wing, A. Preston, E.L. Westman, J.S. Lam, J.H. Naismith, D.J. Maskell and R.A. Field. 2009. Chemical synthesis of uridine 5'-diphospho 2,3-diacetamido-2,3-dideoxy-?-D-glucuronic acid (UDP-Glc-2,3-diNAcA), a key intermediate in cell surface polysaccharide biosynthesis in the human respiratory pathogens Bordetella pertussis and Pseudomonas aeruginosa. Org. Biomol. Chem. 7:1203-1210. (PMID: 19262941)
36. Vinogradov, E., E. Anderson, C. Wilde, A. Nakhamchik, J.S. Lam, and D.A. Rowe-Magnus. 2009. Structure of the lipopolysaccharide core of the Vibrio vulnificus type strain 27562. Carbohydr. Res. 344:484-490. (PMID: 19185290)

Book Chapters (2010-2014)

1. Lam, J.S., E.M. Anderson, and Y. Hao. 2014. LPS quantitation procedures. In: Methods in Pseudomonas, Alain A.M. Filloux and Juan Luis Ramos (ed.) Humana Press. In press.
2. Wakarchuk, W.W. and J.S. Lam. 2012 Microbial glycobiology. In UNESCO Encyclopedia on Life Support Systems (EOLSS). Section 5.25.54
3. Hao, Y., J.S. Lam. 2011. Pathways for the biosynthesis of NDP sugars. In Bacterial lipopolysaccharides: structure, chemical synthesis, biogenesis and interaction with host cells. Y.A. Knirel, and M.A. Valvano (ed). Wien: Springer-Verlag Publishing Inc. Chapter 7, pp. 195-235
4. Westman, E.L., M. Matewish, and J.S. Lam. 2010. "Pseudomonas", In Pathogenesis of Bacterial Infections in Animals, 4th edition, C.L. Gyles, J.F. Prescott, J.G. Songer, and C.O. Thoen. (ed.), Blackwell Publishing, Ch. 23, pp. 443-468.