- Mitochondrial Function and Pathology
- Genomics, phytochemicals, and oxidative stress
- Alzheimer's disease research and treatments
- Coenzyme Q10 studies and effects
- Tryptophan and brain disorders
- DNA and Nucleic Acid Chemistry
- MicroRNA in disease regulation
- Metabolism and Genetic Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetic Neurodegenerative Diseases
- Neurogenesis and neuroplasticity mechanisms
- Cancer Cells and Metastasis
- Biochemical Acid Research Studies
- Nuclear Receptors and Signaling
- Neuroscience and Neuropharmacology Research
- Vitamin C and Antioxidants Research
- Glutathione Transferases and Polymorphisms
- Cancer Research and Treatments
- Cholinesterase and Neurodegenerative Diseases
- RNA Interference and Gene Delivery
- Glycosylation and Glycoproteins Research
- RNA modifications and cancer
- Adipose Tissue and Metabolism
- DNA Repair Mechanisms
- Neurological disorders and treatments
Institute of Cellular and Organismic Biology, Academia Sinica
2020-2022
National Cheng Kung University
2015-2019
Oregon Health & Science University
2010-2018
Institute of Clinical Research
2015
Oregon National Primate Research Center
2010-2012
University of Wisconsin–Madison
2003-2010
Society of Environmental Toxicology and Chemistry
2008-2010
University of California, San Francisco
2004
University of Hong Kong
2004
The antioxidant responsive element (ARE) mediates transcriptional regulation of phase II detoxification enzymes and proteins such as NAD(P)H:quinone oxidoreductase (NQO1), glutathione S-transferases, glutamate-cysteine ligase. In this study, we demonstrate that NF-E2-related factor-2 (Nrf2) plays a major role in activation ARE-driven genes identify Nrf2-dependent by oligonucleotide microarray analysis using primary cortical astrocytes from Nrf2(+/+) Nrf2(-/-) mice. had decreased basal NQO1...
The purpose of our study was to better understand the relationship between mitochondrial structural proteins, particularly dynamin-related protein 1 (Drp1) and amyloid beta (Aβ) in progression Alzheimer's disease (AD). Using qRT-PCR immunoblotting analyses, we measured mRNA levels genes frontal cortex patients with early, definite severe AD control subjects. We also characterized monomeric oligomeric forms Aβ these patients. immunoprecipitation/immunoblotting analysis, investigated...
Increasing evidence suggests that the accumulation of amyloid beta (Aβ) in synapses and synaptic mitochondria causes mitochondrial failure degeneration Alzheimer's disease (AD). The purpose this study was to better understand effects Aβ activity alterations neurons from a mouse model AD. Using primary well-characterized precursor protein transgenic (AβPP) (Tg2576 line), for first time, we studied activity, including axonal transport mitochondria, dynamics, morphology function. Further, also...
NF-E2-related factor 2 (Nrf2) is a basic leucine zipper transcription that binds to the promoter sequence "antioxidant responsive element (ARE)" leading coordinated up-regulation of ARE-driven detoxification and antioxidant genes. Since expression wide array genes are positively regulated by ARE sequence, Nrf2 may serve as master regulator cellular defense system against oxidative stress. In support this, numerous studies have shown protects many cell types organ systems from broad spectrum...
The purpose of our study was to determine the relationship between mutant huntingtin (Htt) and mitochondrial dynamics in progression Huntington's disease (HD). We measured mRNA levels electron transport chain genes, structural Drp1 (dynamin-related protein 1), Fis1 (fission Mfn1 (mitofusin Mfn2 2), Opa1 (optric atrophy Tomm40 (translocase outermembrane 40) CypD (cyclophilin D) grade III IV HD patients controls. Htt oligomers proteins were quantified striatum frontal cortex patients. Changes...
The purpose of this study was to investigate the link between mutant huntingtin (Htt) and neuronal damage in relation mitochondria Huntington's disease (HD). In an earlier study, we determined relationship Htt mitochondrial dynamics/synaptic viability HD patients. We found loss, abnormal dynamics association with current sought expand on our previous findings further elucidate synaptic deficiencies. hypothesized that Htt, mitochondria, alters dynamics, leading fragmentation defective axonal...
Complex II inhibitors 3-nitropropionic acid (3NP) and malonate cause striatal damage reminiscent of Huntington's disease have been shown to involve oxidative stress in their pathogenesis. Because nuclear factor erythroid 2-related 2 (Nrf2)-dependent transcriptional activation by means the antioxidant response element is known coordinate up-regulation cytoprotective genes involved combating stress, we investigated significance Nrf2 complex II-induced toxicity. We found that Nrf2-deficient...
Recent studies indicate that NF-E2 related factor 2 (Nrf2) is a substrate for the ubiquitin-proteasome pathway. The present study aimed to determine whether increased protein stability mechanism by which quinone compounds, like tert-butylhydroquinone (tBHQ), may enhance Nrf2-mediated transcriptional activation and subsequent antioxidant protection. H2O2-induced necrotic cell death, evidenced transmission electronic microscope (TEM) imaging with no caspase 3 PARP cleavage, was significantly...
The purpose of this study was to investigate the protective effects mitochondria-targeted antioxidant catalase (MCAT) and lifespan extension in mice that express amyloid beta (Aβ). Using immunoblotting immunostaining analyses, we measured production full-length precursor protein (APP), soluble APPα, C-terminal fragments CTF99 CTF83, monomeric oligomeric Aβ, Aβ deposits site cleaving enzyme 1 (BACE1), different stages disease progression MCAT/AβPP AβPP mice. quantitative reverse transcriptase...
Triple negative breast cancer (TNBC) lacks both early detection biomarkers and viable targeted therapeutics. Moreover, chemotherapy only produces 20-30% pathologic complete response. Because miRNAs are frequently dysregulated in have broad tissue effects, individual or combinations of circulating may serve as ideal diagnostic, predictive prognostic biomarkers, well therapeutic targets. Understanding the role mechanism TNBC help to develop novel diagnostic strategy for patients.The miRNA...
Nuclear factor E2-related 2 (Nrf2) is a transcription that known to regulate variety of cytoprotective genes through the antioxidant response element (ARE). This endogenous one major pathways by which cells are protected from xenobiotic or innate oxidative insults. Furthermore, in neural systems, astrocyte-specific activation Nrf2 protect neurons. In previous work, our laboratory found protects intrastriatal injections mitochondrial complex II inhibitor malonate. Here, we extend these...
In neuronal systems, the health and activity of mitochondria synapses are tightly coupled. For this reason, it has been postulated that mitochondrial abnormalities may, at least in part, drive neurodegeneration conditions such as Alzheimer’s disease (AD). Mounting evidence from multiple cell mouse models postmortem brains suggest loss integrity may be a key factor mediates synaptic loss. Therefore, prevention or rescue dysfunction help delay altogether prevent AD-associated...
Following the formation of oxidatively-induced DNA damage, several glycosylases are required to initiate repair base lesions that formed. Recently, NEIL1 and other glycosylases, including OGG1 NTH1 were identified as potential targets in combination chemotherapeutic strategies. The therapeutic benefit for inhibition was validated by demonstrating synthetic lethality with drugs commonly used limit replication through dNTP pool depletion via thymidylate synthetase dihydrofolate reductase....
Concurrent chemoradiation therapy (CCRT) is the predominant treatment in esophageal cancer, however resistance to and tumor recurrence are exceedingly common. Elevated ERBB2/Her2 may be at least partially responsible for both high rates of CCRT. This receptor tyrosine kinase upregulated 10-20% squamous cell carcinoma (ESCC) tissues, amplification ERBB2 has been correlated with poor prognosis cancer. Tissues from 131 ESCC patients, along animal models disease were used probe underlying...