One major interest of our laboratory is endothelial cell biology and the role of the endothelium in controlling and modulating vascular tone and vascular growth and hypertrophy. We have been particularly interested in the biochemical and molecular regulation of the vascular nitric oxide-guanylyl cyclase signaling pathway with an emphasis on vascular remodeling in the pulmonary vasculature. Ongoing projects include the molecular mechanisms by which acute and chronic hypoxia regulate this pathway and its role in pulmonary hypertension and pulmonary vascular remodeling, mechanistic studies of feedback regulation of nitric oxide synthase and the interaction of nitric oxide with this and other hemoproteins, oxidative regulation of nitric oxide synthase gene expression, the role of nitric oxide in developmental lung biology, and the role of nitric oxide in regulating gene and protein expression. Recently we have discovered a novel hypoxia-induced mitogenic factor in lung with potent vasoconstricting and angiogenic properties and are actively investigating its function and mechanism of action.

A second major area of interest also involves the nitric oxide guanylyl cyclase signaling pathway, but in relation to its role in mechanisms of anesthesia and analgesia. Interests include the role of the NO pathway in the plasticity associated with hyperalgesia and other pain states, and the mechanisms by which inhibition of the NO signaling pathway enhances the anesthetic state. Currently we are studying the role of molecular scaffolding proteins in the postsynaptic density in hyperalgesia and anesthetic mechanisms.

These research programs are funded by three RO1 grants and a component of a PGA program.

Recent Publications:

Teng X, Li D, Catravas JD, Johns RA: C/EBP- mediates iNOS induction by hypoxia in rat pulmonary microvascular smooth muscle cells. Circ Res 90(2):125-7, 2002

Tao YX, Johns RA: Effect of the deficiency of spinal PSD-95/SAP90 on the minimum alveolar anesthetic concentration of isoflurane in rats. Anesthesiology 94 (6): 1010-1015, 2001

Tao F, Tao YX, Gonzalez JA, Fang M, Mao P, Johns RA: Knockdown of PSD-95/SAP90 delays the development of neuropathic pain in rats. NeuroReport 12(15): 3251-5, 2001

Palmer LA, Gaston B, Johns RA: Normoxic stabilization of hypoxia inducible factor 1 expression and activity: Redox-dependent effect of nitrogen oxides. Mol. Pharmacol. 58 (6): 1197-203, 2000

Fang M, Tao YX, He F, Zhang M, Levine C, Chou CL, Mao P, Sadegh-Nasseri S, Johns RA: Synaptic PDZ protein interactions within the NMDA receptor signaling complex are disrupted by inhalational anesthetics. (in Review)

Tao YX, Rumbaugh G, Wang G-D, Zhao C, Kauer F, Sutter R, O’Brien RJ, Zhuo M, Raja SN, Huganir RL, Bredt DS, Johns RA: Reduction of persistent pain sensation in mice lacking PSD-93. (in Review)

Teng X, Li D, Champion H, Johns RA: Hypoxia Inducible Mitogenic factor: A novel hypoxia inducible mitogenic, angiogenic and vasoconstricting factor in lung. (in Review)