The main theme of my research is hypoxia from physiological adaptation to pathophysiology. Research focuses are on several directions including the ionic mechanisms related to the brain function in hypoxia, and molecular to cellular mechanisms related to cardiopulmonary functions. Using cell models or rodents with prior exposure to hypoxic inspired gases mimicking at high altitude or in diseases such as chronic obstructive pulmonary disease or obstructive sleep apnea, my laboratory has been examining the neural, cardiopulmonary and chemoreceptor responses to a number of circulating hormone such as melatonin or vasoactive substances, such as angiotensin II, endothelin and nitric oxide. Results suggest that these substances and their ligand-binding receptors locally expressed in paracrine/autocrine manner play important physiological roles in the modulation of the excitability of the excitable cells for example. In addition, hypoxia regulates the expression of these substances and the receptors via the HIF-1 pathway and changes the physiological activities in long term. These new findings bring insights to the cellular and molecular mechanisms underlying the acclimatization of the physiological response to hypoxia at high altitude and also have clinical implications in patients with cardiopulmonary or hematological diseases associated with chronic hypoxemia.

Brain ischemia/hypoxia is central to the brain damage in cerebrovascular diseases such as stroke. We are interested in the ionic mechanisms underlying the hypoxia-induced neuronal injuries. We have shown that the influx of extracellular sodium to neurons in the early phase of hypoxia can cause neuronal injuries. We are investigating the roles of the sodium-dependent mechanisms and other ionic mechanisms as well as nitric oxide generation in the hypoxic responses of neurons. The electrical properties of neurons and brain-slices are studied in-vitro using electrophysiological and electrochemical methods.

Previous studies in the neural control of respiration have outlined the organization of both a pontine and a medullary mechanism for the generation and control of eupneic (normal) and gasping (pathophysiological) respiration. We have provided electrophysiological, neuropharmacological, and neuroanatomical data with in vivo studies to extend the understanding of these brainstem mechanisms in neuronal as well as developmental aspects of respiratory control. Ongoing studies are focusing on the roles of vasoactive factors and the molecular mechanisms underlying the sensing of respiratory stimuli, such as hypoxia, by chemoreceptors in the carotid body.