My undergraduate degree was in Biochemistry at Brown University in Providence, RI. I did an undergraduate research project with Dr. Alan Agins in the Department of Molecular Pharmacology. Alan has gone on to bigger and better things as a lecturer on a variety of pharmacological topics. My research project involved assaying for prostaglandin E2 receptors on HL60 promyelocytic leukemia cells.
At Brown, I became interested in the mechanisms that enzymes use to catalyze their reaction and I wanted to explore that area of study in a topic that was broadly related to cancer. I did my graduate work with Dr. William Fahl at the McArdle Laboratory for Cancer Research. My graduate research studied the structure and function of Glutathione S-transferase (GST) an enzyme that detoxifies many electrophilic compounds that can react with DNA to cause damage and mutations. The GST enzyme conjugates the active compounds to glutathione and an export protein then causes the molecule to be removed from the cell. GSTs have broad substrate specificity to allow them to detoxify a variety of compounds. This promiscuity comes with a cost, however, as the GST enzymes are not particularly good enzymes. Essentially, they work badly with a lot of different compounds. Through random mutagenesis and selection, we identified several mutant forms of a GST that were specifically tailored towards a particular substrate.
I did my post-doctoral research with Dr. Ivan Rayment at the Enzyme Institute within the Biochemistry Department at the University of Wisconsin. I worked on several proteins including the motility proteins myosin and a kinesin-like protein called Kar3. I also worked on a family of enzymes from the Enolase superfamily. These enzymes contain TIM-Barrel like structures with low sequence homology to each other. The enzymes use very subtle changes in active site residues to catalyze different reactions. All of the enzymes share a similar chemical step (removal of a proton alpha to a carboxylate group). What the enzymes do with the enolate intermediate, however, differs from enzyme to enzyme.