Research InterestsMolecular chaperones; misfolded proteins and disease; Parkinson’s disease; metabolism and cancer; small molecule screening. 1. Parkinson's disease. We have developed a unique model of Parkinson’s disease in which we express alpha-synuclein (a protein implicated as the causative agent of Parkinson’s disease) in budding yeast. This yeast model permits us to carry out genetic experiments that probe the mechanism of alpha-synuclein toxicity. The objective is to find therapeutic agents that halt the progression of Parkinson’s disease. 2. Metabolism and cell death. We use yeast to investigate a unique form of cell death called sugar-induced apoptosis. We believe that this form of cell death models type 2 diabetes. Experiments are designed to find novel compounds that inhibit sugar-induced cell death and to identify the genes that regulate this cell death pathway. 3. The Krebs cycle and cancer. We are using yeast to screen for small molecules that inhibit the various enzymes of the glycolytic pathway. In many cancers, cells gain energy almost exclusively through aerobic glycolysis rather than through respiration. One possible treatment for such cancers is to use drugs that target the glycolytic enzymes. We are screening thosands of compounds to find those that target glycolytic enzymes.
Specialized Techniques/Procedures Chromatography of Proteins: SDS-PAGE Size-exclusions chromatography Western blotting Confocal & fluorescence microscopy & EM Spectroscopy: Circular dichroism Steady-state and stopped-flow fluorescence Surface plasmon resonance Yeast genetics