Hypoxia sensing by non-heme Fe(II) oxygenases

Hypoxia sensing is crucial to how human cells sense O2 and develop into tissues. We study the mechanism and inactivation of HIF-hydroxylases, Fe(II) enzymes that are key hypoxia sensors for humans, in order to relate the atomic details of enzyme function to cellular O2 sensing. The biomedical impact of this work is very high, as the O2-reactivity and regulation of these HIF-hydroxylases (called FIH-1 and PHD) may impact diseases involving angiogenesis or oxygen toxicity. This NIH-funded project is well positioned to advance the understanding of O2-activation chemistry as well as the chemistry of hypoxia sensing.


Recombinant protein expression and activity assays for the HIF-hydroxylases

Discovered auto-hydroxylation pathway in FIH-1

Proposed protein maturation pathway for FIH-1