Harvard Medical School
HIM Room 1013
4 Blackfan Circle
Boston MA 02115
Lab Size: Between 15-20
The Walker Group has expertise in studying bacterial cell wall biosynthesis and its inhibition. We have developed chemical approaches to study the membrane-linked steps of peptidoglycan and teichoic acid biosynthesis, and have made fundamental contributions to understanding the enzymes involved in these processes and the mechanisms of action of antibiotics that inhibit them. We work on Gram positive organisms, including the pathogens Staphylococcus aureus and Enterococcus faecalis, and a major research focus includes exploring novel strategies to overcome antibiotic resistant microorganisms. My research program combines organic chemistry, enzymology, high throughput screening, biophysics, and bacterial genetics to address problems of interest.
1. Lazarus MB, Jiang J, Gloster TM, Zandberg WF, Whitworth GE, Vocadlo DJ, Walker S*. Structural snapshots of the reaction coordinate for O-GlcNAc transferase. Nat. Chem. Biol. 2012; 8:966-8.
2. Lazarus MB, Jiang J, Kapuria V, Bhuiyan T, Janetzko J, Zandberg WF, Vocadlo DJ, Herr W, Walker S*. HCF-1 is cleaved in the active site of O-GlcNAc transferase. Science 2013; 342:1235-9.
3. Schaefer K, Matano LM, Qiao Y, Kahne D, Walker S*. In vitro reconstitution demonstrates the cell wall ligase activity of LCP proteins. Nat. Chem. Biol. 2017; 13:396-401.
4. Martin SES, Tan ZW, Itkonen HM, Duveau DY, Paulo JA, Janetzko J, Boutz PL, Törk L, Moss FA, Thomas CJ, Gygi SP, Lazarus MB*, Walker S*. Structure-Based Evolution of Low Nanomolar O-GlcNAc Transferase Inhibitors. J. Am. Chem. Soc. 2018; 140:13542-45.
5. Taguchi A, Welsh MA, Marmont LS, Lee W, Sjodt M, Kruse AC, Kahne D, Bernhardt TG*, Walker S*. FtsW is a peptidoglycan polymerase that is functional only in complex with its cognate penicillin-binding protein. Nat. Microbiol. 2019; 4:587-94.