Research Associate Professor
Phone: (979) 862-4973
The research interests include astroglial cell biology and heavy metal neurotoxicity. The studies have identified that Pb deposit in astrocytes competitively with copper (Cu) binds to heavy metal binding (HMB) domain of ATP7A, a Cu-transporting ATPase that contributes to Cu release, leading to Cu accumulation intracellularly and the promotion of reactive oxygen species (ROS) production that both have been involved in neurodegenerative diseases including Alzheimer’s disease and amyotrophic lateral sclerosis. The studies have also identified a 78 kD glucose-regulated protein (GRP78), also named as HSPA5 or BiP, as one of Pb targets. GRP78 is an endoplasmic reticulum-resident molecular chaperone functioning in protein folding, assembly and trafficking in posttranslational quality control and also plays a role in protection against cytotoxicity and apoptosis induced by environmental insults. Emerging evidence indicates that the protein is involved in cancers including breast cancers, lung cancers, and others and neurodegenerative disorders including Alzheimer's disease. The studies demonstrate that Pb directly binds to GRP78 and the binding plays a “double-edged sword” role because it protects the cells from the toxicity of free Pb ions but also reduces protein secretion (e.g. IL-6) and Cu release from astrocytes. Current interests are focused on functions of GRP78 in Cu homeostasis and glucose utilization of the central nervous system that both are involved in neurodegenerative disorders and cancers.
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