Reactive Oxidants and Signaling

The study of reactive oxidant species (ROS) has long been dominated by the concept that ROS are primarily of biomedical importance because of their capacity to initiate damaging reactions that cause oxidative stress and cellular injury.

Only recently has it become clear that most if not all multicellular organisms have evolved enzymatic complexes whose primary product is superoxide anion, indicating a conserved, adaptive function for regulated ROS production.

The NADPH oxidase (Nox) family members are prototypical of such enzymes; thus the examination of Nox biology reveals much about the cellular logic behind regulated oxidant production.

The Nox genes are conserved from filamentous fungi and slime molds, and control differentiation responses. In humans, the seven known Noxs, including Nox1-5 and Duox1-2, regulate a number of pathways upstream of Ras, MAPK, JAK/STAT, and NF-κB.

Our lab focuses on the use of Nox enzymes to spatially and temporally control ROS to focus their effects for homeostatic signaling. We study the role of Nox 2 in Rac-dependent signaling at nascent integrin structures called focal complexes, and on the site-specific effects of Nox4 on triggering Ras activation on the surface of the endoplasmic reticulum in response to an accumulation of misfolded client proteins.