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, αKG-dependent oxygenases, but their unique role leads to interesting mechanisms, including inactivation pathways involving ROS release or autohydroxylation.



In addition to mechanistic studies to identify reactivities and new substrate, we are looking at the HIF hydroxylases as engineering templates to redesign the active site for new chemistry.