Ph.D. Univ. of California, San Diego
One of our research interests is to study the pathogenesis of and neuroprotection against Alzheimer’s disease (AD). Recently, we have found that galectin-3 promotes neuroinflammation and contributes significantly to the pathogenesis of AD. The expression level of galectin-3 is increased in the hippocampus of APP/PS1 mice at very early stage and could be considered as a biomarker and novel therapeutic target for AD. In studying the neuroprotection against AD, we have found that protein SUMOylation plays an important role in this process. For example, SUMOylation of Elk-1 decreases GADD45α expression and reduces the number of apoptotic neurons in the hippocampus of APP/PS1 mice. SUMOylation of AICD increases AICD nuclear translocation, increases the expression of neprilysin and transthyretin and enhances amyloid-beta degradation in APP/PS1 mice. We are currently examining the neuroprotective role and molecular mechanism of APP SUMOylation. We also aim at identifying endogenous stimuli that induce APP SUMOylation. Moreover, we are exploring other endogenous protection mechanisms against AD. These results together should provide novel insights and therapeutic strategies against AD.
In addition, we are also interested in studying the neural and molecular mechanisms of mammalian long-term memory formation. Upon identification of a novel candidate gene, we further study the expression, signaling pathway and regulation mechanism of this gene involved in memory formation. By using the differential display PCR (DD-PCR) strategy, we have previously identified the serum- and glucocorticoid-inducible kinase (sgk) gene and the protein inhibitor of activated STAT1 (pias1) gene involved in memory processing. Identification of the sgk gene provides novel molecular mechanism underlying glucocorticoid-induced memory facilitation in humans and animals. Identification of the pias1 gene reveals that protein SUMOylation is a novel and important mechanism underlying long-term memory formation. By using the same DD-PCR strategy, we have recently indentified other candidate genes that play novel roles in regulating long-term memory formation in rats and mice. We are currently investigating the molecular mechanisms underlying these regulations.
Identification of Ndfip1 as a novel negative regulator for spatial memory formation associated with increased ubiquitination of Beclin 1 and PTENPLoS One, Apr 06, 2023
Melatonin Induction of APP Intracellular Domain 50 SUMOylation Alleviates AD through Enhanced Transcriptional Activation and Aβ DegradationMolecular Therapy, Sep 05, 2020