Research Overview and Links
My research focuses on the development of inhibitors of zinc metalloenzymes.
We are currently developing inhibitors of a bacterial enzyme called LuxS. LuxS is the last enzyme in a biosynthetic pathway that makes bacterial signaling molecules called autoinducers. Autoinducers are used by bacteria to sense thier local population in a phenomenon called quorum sensing. Quorum sensing triggers behavioral changes in bacteria including virulence in such species as Salmonella, pathogenic E. coli, Vibrio cholera, and the Lyme disease spirochette. Blocking production of quorum sensing signals by LuxS inhibition may be a way to treat pathologies triggered by quorum sensing without killing the offending bacteria, lessening the likelihood of drug resistance.
We are also interested in developing new, specific inhibitors of zinc-dependent histone deacetylases or "HDACs". HDACs control the patterns of gene activation that change during development as well as tumorigenesis. There is a significant need for HDAC-specific inhibitors to elucidate their roles in these key biological processes.
Our third and newest project deals with generating inhibitors of a bacterial enzyme called peptidoglycan deacetylase or Pgda. Peptidoglycan is a major component of bacterial cell walls, and its modification by Pgda "hides" it from the digestive action of lysozyme, which is an enzyme that fights infection. Thus, inhibiting Pgda should help in the clearance of bacterial infections.
For each project students often learn various techniques such as organic synthesis, basic molecular biology, protein expression/purification and enzymology.
Current research students:
Keris KrennHrubec, Biochemistry '08, ; Pamela Ronco, Biochemistry '08; Colleen O'Loughlin, Biochemistry '09.
Former research students:
