Research Interests
Acid-sensing ion channels One
major project in Dr. Xiong's laboratory is to study the molecular
mechanisms underlying acidosis-mediated brain injury. During
hypoxia/ischemia, for example, increased anaerobic glycolysis due to the
lack of blood and oxygen supply leads to lactic acid accumulation,
causing decreases in brain pH, a phenomenon termed acidosis.
Extracellular pH typically falls to 6.5 during ischemia, and can fall
below 6.0 during severe ischemia or under hyperglycemic conditions (e.g.
in diabetic patients). For many years, acidosis has been known to play
an important role in the pathology of neuronal injury. However, the
cellular and molecular mechanisms underlying acidosis-mediated brain
injury remained hypothetical, multifactorial and vague. Recent studies
by Dr. Xiong's lab and his collaborators have demonstrated that
activation of acid-sensing ion channels (ASICs), a novel family of
proton-gated cation channels, and subsequent intracellular calcium
overload, plays an important role in acidosis-mediated,
glutamate-independent neuronal injury (Cell 118: 687-98, 2004). The
blockade of these channels showed a promising protective time window of
more than 5 hours (Brain 130:151-8, 2007). Thus, ASICs represent novel
therapeutic targets for ischemic brain injury. Current studies in the
lab focus on down-stream signaling pathways involved in the activation
of ASICs, on targeting mechanisms of these channels to the cell surface
membrane, on changes in the expression of ASICs, and on modulations of
the channels by ischemia-related signaling molecules. The roles of ASICs
in other neurological disorders are under active investigation.
TRPM7 channels
Transient
receptor potential (TRP) channels belong to a novel family of cation
channels that are highly expressed in various tissues including the
brain. Several members of the TRP family can be activated by oxidative
stress and oxygen free radicals, both of which play important roles in
neuronal injury associated with neurological disorders. Recent work by
Dr. Xiong’s laboratory and his collaborators have indicated that calcium and/or zinc
entry through TRPM7 channels, a member of the melastatin
subfamily of the TRP channels, plays a key role in neuronal cell death
associated with brain ischemia (Cell, 115: 863-77, 2003; JBC 285:
7430-9, 2010). The role of TRPM7 channels in other neurological
diseases is also under investigation.
Current Grant Support
National Institute of Health (NIH)
American Heart Association (AHA)
Alzheimer’s Association (ALZ)
Editorial Responsibility
International Journal of Physiology Pathophysiology and Pharmacology, Editor-in-Chief
Neurological Research, Editorial Board Member
International Journal of Experimental and Clinical Medicine, Editorial Board Member