Biological and Inorganic Chemistry
Enzyme structure and mechanisms, Hypoxia sensing, Metalloenzymes, Redesign of the second coordination sphere
BS 1993, University of California, San Diego PhD 1998, University of California, San Diego NIH Postdoctoral Fellow 1998-2002, University of California, Berkeley
512 LGRT Tower A
Principal Research Interests
The response to low [O2] (hypoxia) is crucial for cellular growth, proliferation, and proliferative disease states. My group focuses on the HIF hydroxylases, FIH and PHD, which are human O2-sensing enzymes that hydroxylate specific protein residues on the HIF transcription factor.
These HIF-hydroxylases are nonheme Fe, aKG-dependent oxygenases, but their unique role leads to interesting mechanisms. In addition to mechanistic studies to identify novel intermediates, we are looking at the HIF hydroxylases as engineering templates to create alternate rebound chemistry for protein labeling.
Enzyme inhibition and activation:
Developing screening methods for inhibitor screens of HIF hydroxylases is an enormous challenge, as these are metalloenzymes. My group combines spectroscopy, crystallography, and medium-throughput binding assays to screen for inhibitors.
Activating enzymes would open up new directions for discovering disease pathways. Enzyme delivery is one approach, presenting new opportunities for therapeutics. We are collaborating with nanotechnology researchers to target active enzymes into cells.
Explosives detection is of great interest, as well as being an excellent theme to explore chemical sensing approaches. We are developing fluorescent Zn(salophen) complexes for new explosives-detection strategies. This work also tests Zn(salophen) complexes that show promise for cellular imaging.