Oxidant stress plays contradicting roles in the cellular adaptation to hypoxia and ischemia, with low levels involved in triggering protective events such as Hypoxia Inducible Factor (HIF) stabilization, and higher levels associated with oxidative damage to DNA, lipids and proteins. Our experiments show that endogenous reactive oxygen species (ROS) mediate activation of AMP-activated Protein Kinase (AMPK), a key sensor of cellular energy balance which is highly conserved in all eukaryotic cells. My project involves investigating the role of ROS in AMPK signaling, describing an ROS mediated pathway for AMPK activation and studying the effects of this pathway on cell survival.

Peer-Reviewed Publications:

Gupta, M., Mungai, P.T. and Goldwasser, E. A new transacting factor that modulates hypoxia-induced expression of the erythropoietin gene. Blood, 96:491-497, 2000.

Pearlstein, D.P., Ali, M.H., Mungai, P.T., Hynes, K.L., Gewerz, B.L. and Schumacker,  P.T. Role of mitochondrial oxidant generation in endothelial cell responses to hypoxia. Arterioscler. Thromb. Vasc. Biol., 22:566-573, 2001.

Waypa, G.B., Marks, J.D., Mack, M.M., Boriboun, C., Mungai, P.T. and Schumacker, P.T. Mitochondrial reactive oxygen species trigger calcium increases during hypoxia in pulmonary arterial myocytes. Circ Res. 91:719-726, 2002.

Ali, M.H., Mungai, P.T. and Schumacker, P.T. Stretch-induced phosphorylation of focal adhesion kinase in endothelial cells: role of mitochondrial oxidants. Am. J. Physiol. Lung Cell. Mol. Physiol., Jul 29, 1(1):L38-45, 2006.

Waypa, G.B., Guzy, R., Mungai, P.T., Mack, M.M., Marks, J.D., Roe, M.W. and Schumacker, P.T. Increases in mitochondrial reactive oxygen species trigger hypoxia-induced calcium responses in pulmonary artery smooth muscle cells. Circ. Res., Oct 27, 99(9):970-8, 2006.

Abstracts:

Mungai, P.T. and Schumacker, P.T., ROS Mediated Activation of AMP-activated Protein Kinase (AMPK) During Hypoxia and Ischemia in Cells. Submitted for the 2008 Keystone Hypoxia Conference.