description): The overall program hypothesis is that oxygen deprivation leads to alterations in cytosolic, membrane and nuclear events that form the underlying basis for cellular adaptation, sublethal injury or cell death. The extent of these alterations depends on many factors including age, type of cell and its endowments in both excitable (e.g. neurons) and non-excitable cells (e.g. glia, renal tubular epithelium), and severity and chronicity of hypoxia. The central aims of this program are therefore to: 1) define the nature of the response to hypoxia in neurons, glia and renal tubular epithelium in mature and immature cells; and 2) delineate the underlying mechanisms at the cellular and molecular level. To address these aims and determine the mechanisms that can lead to injury or adaptation and survival in the mature and immature cell, four projects and three cores are proposed. To accomplish these aims, the investigators will use state-of-the-art techniques and methodologies including electrophysiologic methods, electron, immunofluorescent, confocal and video-microscopy, Nuclear Magnetic Resonance, and molecular biologic techniques to study native tissue, tissue slices, dissociated and cultured cells.
| Azad, Priti; Zhao, Huiwen W; Cabrales, Pedro J et al. (2016) Senp1 drives hypoxia-induced polycythemia via GATA1 and Bcl-xL in subjects with Monge's disease. J Exp Med 213:2729-2744 |
| Yao, Hang; Azad, Priti; Zhao, Huiwen W et al. (2016) The Na+/HCO3- co-transporter is protective during ischemia in astrocytes. Neuroscience 339:329-337 |
| Jha, Aashish R; Zhou, Dan; Brown, Christopher D et al. (2016) Shared Genetic Signals of Hypoxia Adaptation in Drosophila and in High-Altitude Human Populations. Mol Biol Evol 33:501-17 |
| Pamenter, Matthew E; Haddad, Gabriel G (2015) High-throughput cell death assays. Methods Mol Biol 1254:153-63 |
| Salameh, Ahlam Ibrahim; Ruffin, Vernon A; Boron, Walter F (2014) Effects of metabolic acidosis on intracellular pH responses in multiple cell types. Am J Physiol Regul Integr Comp Physiol 307:R1413-27 |
| Gu, Xiang Q; Pamenter, Matthew E; Siemen, Detlef et al. (2014) Mitochondrial but not plasmalemmal BK channels are hypoxia-sensitive in human glioma. Glia 62:504-13 |
| Gersten, Merril; Zhou, Dan; Azad, Priti et al. (2014) Wnt pathway activation increases hypoxia tolerance during development. PLoS One 9:e103292 |
| Udpa, Nitin; Ronen, Roy; Zhou, Dan et al. (2014) Whole genome sequencing of Ethiopian highlanders reveals conserved hypoxia tolerance genes. Genome Biol 15:R36 |
| Douglas, Robert M; Chen, Alice H; Iniguez, Alejandra et al. (2013) Chemokine receptor-like 2 is involved in ischemic brain injury. J Exp Stroke Transl Med 6:1-6 |
| Parker, Mark D; Boron, Walter F (2013) The divergence, actions, roles, and relatives of sodium-coupled bicarbonate transporters. Physiol Rev 93:803-959 |
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