CSB Seminar – Professor Rachel Brewster, University of Maryland

Prolonged oxygen deprivation results in irreversible cellular damage in humans, as a result of impaired oxidative phosphorylation and the ensuing drop in cellular energy (ATP). Hence it is not surprising that ischemic injury is a leading cause of morbidity and mortality worldwide. However, some organisms, such as the zebrafish embryo, have adaptive mechanisms that prevent them from completely expending ATP under low oxygen conditions. These processes are not well understood, but a prevailing idea is that arrest of activity or suspended animation prevents complete depletion of ATP. Remarkably, zebrafish embryos can survive for up to 50 hours in this hypometabolic state, in complete absence of oxygen (anoxia), and resume activity once normal oxygen is restored. Understanding the signaling events that trigger arrest and entry into a hypometabolic state in this organisms may thus provide valuable insights on targets for the prevention and treatment of ischemic injuries. Research in the Brewster lab currently focuses on unraveling the role and regulation of N-myc Downstream Regulated (NDRG) proteins in molecular adaptation to low oxygen. These stress response proteins are expressed in a tissue-restricted manner in organs and tissues that consume high levels of oxygen to maintain the activity of ATP-demanding pumps. The function of NDRG1 in promoting a hypometabolic state in the embryonic kidney will be discussed.