Our laboratory focuses on the mechanisms by which cells maintain homeostasis of iron and oxygen, with particular attention to hypoxia-inducible factors (HIFs) and iron regulatory proteins (IRPs).
We have identified regulatory factors for each pathway that sense both iron and oxygen levels and maintain mammalian iron and oxygen homeostasis at both the cellular and systemic levels: hydroxylases for HIF and the hemerythrin-containing FBXL5 for IRPs.
We have also found that overlapping control of gene expression creates cross-talk between the HIF and IRP pathways, and are investigating new mechanisms by which various metabolites influence these pathways. With these findings, we search for small-molecule antagonists of the pathways to validate their potential as therapeutic targets.
Our observations provide new insights and opportunities to address diseases stemming from misregulation of oxygen and iron homeostasis including anemia, iron overload disorders, infection, stroke, heart attack, and cancer.