A5050492618- Mitochondrial Function and Pathology
- Epigenetics and DNA Methylation
- Endoplasmic Reticulum Stress and Disease
- Genetics, Aging, and Longevity in Model Organisms
- Autophagy in Disease and Therapy
- Liver Disease Diagnosis and Treatment
- Genetics and Neurodevelopmental Disorders
- Metabolism and Genetic Disorders
- Hepatitis B Virus Studies
- MicroRNA in disease regulation
- RNA modifications and cancer
- Genetic Syndromes and Imprinting
- Adipose Tissue and Metabolism
- Liver physiology and pathology
- Metalloenzymes and iron-sulfur proteins
- Amino Acid Enzymes and Metabolism
- Prenatal Screening and Diagnostics
- Ubiquitin and proteasome pathways
- Metabolomics and Mass Spectrometry Studies
- Cancer-related Molecular Pathways
- Folate and B Vitamins Research
- Microtubule and mitosis dynamics
- Pancreatic function and diabetes
- Cancer, Hypoxia, and Metabolism
- Cancer-related gene regulation
National Yang Ming Chiao Tung University
2016-2025
National Health Research Institutes
2016-2025
China Medical University
2025
China Medical University Hospital
2025
National Chiayi University
2023
Academia Sinica
2016-2020
University of California Davis Medical Center
2013-2017
National Taiwan University Hospital
2015
National Taiwan University
2015
National Yang Ming University Hospital
2009-2014
MicroRNA-122 (miR-122), which accounts for 70% of the liver's total miRNAs, plays a pivotal role in liver. However, its intrinsic physiological roles remain largely undetermined. We demonstrated that mice lacking gene encoding miR-122a (Mir122a) are viable but develop temporally controlled steatohepatitis, fibrosis, and hepatocellular carcinoma (HCC). These exhibited striking disparity HCC incidence based on sex, with male-to-female ratio 3.9:1, recapitulates disease humans. Impaired...
CISD2 , the causative gene for Wolfram syndrome 2 (WFS2), is a previously uncharacterized novel gene. Significantly, located on human chromosome 4q, where genetic component longevity maps. Here we show first time that involved in mammalian life-span control. Cisd2 deficiency mice causes mitochondrial breakdown and dysfunction accompanied by autophagic cell death, these events precede two earliest manifestations of nerve muscle degeneration; together, they lead to panel phenotypic features...
In hepatocellular carcinoma (HCC), dysregulated expression of microRNA-224 (miR-224) and impaired autophagy have been reported separately. However, the relationship between them has not explored. this study we determined that is down-regulated inversely correlated with miR-224 in hepatitis B virus (HBV)-associated HCC patient specimens. These results were confirmed liver tumors HBV X gene transgenic mice. Furthermore, was preferentially recruited degraded during autophagic progression...
Dysfunction of degradation machineries causes cancers, including hepatocellular carcinoma (HCC). Overexpression cyclin D1 in HCC has been reported. We previously reported that autophagy preferentially recruits and degrades the oncogenic microRNA (miR)‐224 to prevent HCC. Therefore, present study, we attempted clarify whether is another factor selectively regulated by tumorigenesis. Initially, found an inverse correlation between low autophagic activity high expression tumors 147 patients...
Abstract The ubiquitin–proteasome system (UPS) and autophagy are two major quality control processes whose impairment is linked to a wide variety of diseases. coordination between UPS remains incompletely understood. Here, we show that ubiquitin ligase UBE3C deubiquitinating enzyme TRABID reciprocally regulate K29/K48-branched ubiquitination VPS34. We find this enhances the binding VPS34 proteasomes for degradation, thereby suppressing autophagosome formation maturation. Under ER proteotoxic...
Abstract Background CDGSH iron-sulfur domain-containing protein 2 (CISD2), a pro-longevity gene, mediates healthspan in mammals. CISD2 is down-regulated during aging. Furthermore, persistently high level of promotes longevity and ameliorates an age-related skin phenotype transgenic mice. Here we translate the genetic evidence into pharmaceutical application using potent activator, hesperetin, which enhances expression HEK001 human keratinocytes from older person. We also treated naturally...
Ground glass hepatocytes (GGH) in chronic hepatitis B virus (HBV) infection harbor HBV pre-S deletion mutants endoplasmic reticulum (ER) and exhibit complex biologic features such as ER stress, DNA damage, growth advantage. The presence of serum has been shown to predict the development hepatocellular carcinoma (HCC) carriers. GGHs hence represent a potentially preneoplastic lesion. Whether specific factor is overexpressed activated remains be clarified. In this study, factor(s) up-regulated...
In contrast to somatic cells, formation of acentriolar meiotic spindles relies on the organization microtubules (MTs) and MT-organizing centers (MTOCs) into a stable bipolar structure. The underlying mechanisms are still unknown. We show that this process is impaired in hepatoma up-regulated protein (Hurp) knockout mice, which viable but female sterile, showing defective oocyte divisions. HURP accumulates interpolar MTs vicinity chromosomes via Kinesin-5 activity. By promoting MT stability...
Abstract Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) occurs predominantly in men. By enhancing the transcriptional activity of androgen receptor (AR) gene a ligand-dependent manner, HBV X protein (HBx) might contribute to this disparity between sexes. To dissect mechanisms underlying HBx-enhanced AR transactivation, we investigated effect HBx on two critical steps regulation ligand-stimulated activities. One step is dimerization (through interaction its N-termini and...
CLEC4F, a member of C-type lectin, was first purified from rat liver extract with high binding affinity to fucose, galactose (Gal), N-acetylgalactosamine (GalNAc), and un-sialylated glucosphingolipids GalNAc or Gal terminus. However, the biological functions CLEC4F have not been elucidated. To address this question, we examined expression distribution murine determined its specificity by glycan array, investigated function using knockout (Clec4f−/−) mice. We found that is heavily...
CISD2 is a causative gene associated with Wolfram syndrome (WFS). However, it remains mystery as to how the loss of causes metabolic defects in patients WFS. Investigation on role played by Cisd2 specific cell types may help us resolve these underlying mechanisms. White adipose tissue (WAT) central maintenance energy metabolism and glucose homeostasis humans. In this study, adipocyte-specific knockout (KO) mice showed impairment development epididymal WAT (eWAT) autonomous manner. A lack...
The CISD2 gene, which is an evolutionarily conserved novel encodes a transmembrane protein primarily associated with the mitochondrial outer membrane. Significantly, gene located within candidate region on chromosome 4q where genetic component for human longevity has been mapped. Previously, we have shown that Cisd2 deficiency shortens lifespan resulting in premature aging mice. Additionally, age-dependent decrease expression detected during normal aging. In this study, demonstrate...
CISD2 is located within the chromosome 4q region frequently deleted in hepatocellular carcinoma (HCC). Mice with Cisd2 heterozygous deficiency develop a phenotype similar to clinical manifestation of nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH). haploinsufficiency causes low incidence (20%) spontaneous HCC promotes HBV-associated DEN-induced HCC; conversely, 2-fold overexpression suppresses these models. Mechanistically, interacts Serca2b mediates its Ca2+ pump...
Abstract Background The human CISD2 gene is located within a longevity region mapped on chromosome 4q. In mice, Cisd2 levels decrease during natural aging and genetic studies have shown that high level of prolongs mouse lifespan healthspan. Here, we evaluate the feasibility using activator as an effective way delaying aging. Methods Hesperetin was identified promising by herb compound library screening. has no detectable toxicity based in vitro vivo models. Naturally aged mice fed dietary...
Abstract Wolfram syndrome is a rare genetic disease caused by mutations in the WFS1 or CISD2 gene. A primary defect involves poor ER Ca 2+ handling, but how this disturbance leads to not known. The current study, performed neurons, most affected and disease-relevant cells, involving both genes, explains disturbed handling compromises mitochondrial function affects neuronal health. Loss of content impaired ER-mitochondrial contact sites WFS1- CISD2-deficient neurons associated with lower IP 3...
Prader-Willi syndrome (PWS) and Angelman (AS) are caused by deficiency of imprinted gene expression from paternal or maternal chromosome 15q11–q13, respectively. Genomic imprinting the PWS/AS domain is regulated through a bipartite cis -acting center (PWS-IC/AS-IC) within upstream SNRPN promoter. Here, we show that two Rb-binding protein-related genes, Rbbp1 / Arid4a Rbbp1l1 Arid4b , involved in regulation IC. We recovered these genes trap mutagenesis selecting for altered an Snrpn -EGFP...
Glycine N-methyltransferase (GNMT) affects genetic stability by regulating DNA methylation and interacting with environmental carcinogens. To establish a Gnmt knockout mouse model, 2 lambda phage clones containing genome were isolated. At 11 weeks of age, the Gnmt−/− mice had hepatomegaly, hypermethioninemia, significantly higher levels both serum alanine aminotransferase hepatic S-adenosylmethionine. Such phenotypes mimic patients congenital GNMT deficiencies. A real-time polymerase chain...
Hepatocellular carcinoma (HCC) is the fifth common cancer in world and it mainly occurs men. Glycine N-methyltransferase (GNMT) participates one-carbon metabolism affects DNA methylation by regulating ratio of S-adenosylmethionine to S-adenosylhomocystine. Previously, we described that expression GNMT was diminished human HCC. Here, showed 50% (3/6) male 100% (7/7) female Gnmt-/- mice developed HCC, their mean ages HCC development were 17 16.5 months, respectively. In addition, 42.9% (3/7)...