- Pancreatic function and diabetes
- Metabolism, Diabetes, and Cancer
- Adipose Tissue and Metabolism
- Endoplasmic Reticulum Stress and Disease
- Peroxisome Proliferator-Activated Receptors
- Cancer-related gene regulation
- Liver Disease Diagnosis and Treatment
- Lipid metabolism and biosynthesis
- FOXO transcription factor regulation
- Epigenetics and DNA Methylation
- Diet, Metabolism, and Disease
- Cholesterol and Lipid Metabolism
- Cancer, Hypoxia, and Metabolism
- RNA Research and Splicing
- Liver physiology and pathology
- Hormonal Regulation and Hypertension
- Diabetes Treatment and Management
- Cannabis and Cannabinoid Research
- Estrogen and related hormone effects
- Adipokines, Inflammation, and Metabolic Diseases
- Autophagy in Disease and Therapy
- Nuclear Receptors and Signaling
- TGF-β signaling in diseases
- RNA regulation and disease
- PI3K/AKT/mTOR signaling in cancer
Korea University
2015-2024
Pusan National University
2024
Sungkyunkwan University
2005-2013
Samsung (South Korea)
2010-2013
GTx (United States)
2012
Samsung (United Kingdom)
2011
Kosin University
2010
Salk Institute for Biological Studies
2003-2006
Beth Israel Deaconess Medical Center
2005
Massachusetts General Hospital
2005
The Peutz-Jegher syndrome tumor-suppressor gene encodes a protein-threonine kinase, LKB1, which phosphorylates and activates AMPK [adenosine monophosphate (AMP)-activated protein kinase]. deletion of LKB1 in the liver adult mice resulted nearly complete loss activity. Loss function hyperglycemia with increased gluconeogenic lipogenic expression. In LKB1-deficient livers, TORC2, transcriptional coactivator CREB (cAMP response element-binding protein), was dephosphorylated entered nucleus,...
Hormones and nutrients often induce genetic programs via signaling pathways that interface with gene-specific activators. Activation of the cAMP pathway, for example, stimulates cellular gene expression by means PKA-mediated phosphorylation cAMP-response element binding protein (CREB) at Ser-133. Here, we use genome-wide approaches to characterize target genes are regulated CREB in different contexts. was found occupy ≈4,000 promoter sites vivo , depending on presence methylation state...
FoxO transcription factors are important targets of insulin action. To better understand the role proteins in liver, we created transgenic mice expressing constitutively active FoxO1 liver using alpha1-antitrypsin promoter. Fasting glucose levels increased, and tolerance is impaired (TGN) versus wild type (WT) mice. Interestingly, fasting triglyceride cholesterol reduced despite hyperinsulinemia, post-prandial changes markedly suppressed TGN WT Activation pro-lipogenic signaling pathways...
Orphan nuclear receptor small heterodimer partner (SHP) plays a key role in transcriptional repression of gluconeogenic enzyme gene expression. Here, we show that SHP inhibited protein kinase A-mediated activity cAMP-response element-binding (CREB), major regulator glucose metabolism, to modulate hepatic Deletion analysis phosphoenolpyruvate carboxykinase (PEPCK) promoter demonstrated forskolin-mediated induction PEPCK transcription via inhibition CREB activity. In vivo imaging...
The regulation of M1/M2 polarization in liver macrophages is closely associated with the progression nonalcoholic steatohepatitis (NASH); however, mechanism involved this process remains unclear. Here, we describe orphan nuclear receptor retinoic-acid-related α (RORα) as a key regulator hepatic residential Kupffer cells (KCs) and infiltrated monocyte-derived macrophages. RORα enhanced M2 KCs by inducing kruppel-like factor 4. was defective bone-marrow-derived myeloid-specific null mice,...
Protein arginine methyltransferases (PRMTs) have emerged as important regulators of skeletal muscle metabolism and regeneration. However, the direct roles various PRMTs during remodeling remain unclear. Using muscle-specific prmt1 knockout mice, we examined function downstream targets PRMT1 in homeostasis. We found that deficiency led to atrophy. PRMT1-deficient muscles exhibited enhanced expression a macroautophagic/autophagic marker LC3-II, FOXO3 ubiquitin ligases, TRIM63/MURF-1 FBXO32,...
Olfactory receptors (ORs) are present in tissues outside the olfactory system; however, function of these remains relatively unknown. Here, we determined that receptor 544 (Olfr544) is highly expressed liver and adipose tissue mice regulates cellular energy metabolism obesity. Azelaic acid (AzA), an Olfr544 ligand, specifically induced PKA-dependent lipolysis adipocytes promoted fatty oxidation (FAO) ketogenesis liver, thus shifting fuel preference to fats. After 6 weeks administration, fed...
Sterol regulatory element-binding proteins (SREBPs) activate genes of cholesterol and fatty acid metabolism. In each case, a ubiquitous co-regulatory factor that binds to neighboring recognition site is also required for efficient promoter activation. It likely gene- pathway-specific regulation by the separate SREBP isoforms dependent on subtle differences in how individual function with specific co-regulators gene expression. studies reported here we extend these observations significantly...
Transcription of a number genes involved in lipogenesis is stimulated by dietary carbohydrate the mammalian liver. Both insulin and increased glucose metabolism have been proposed to be initiating signals for this process, but pathways which these effectors act alter transcription not resolved. We previously defined electrophoretic mobility shift assay factor nuclear extracts from rat liver, designated carbohydrate-responsive (Cho- RF), that binds liver-type pyruvate kinase S(14) promoters...
It has been reported that peroxisome proliferator-activated receptor (PPAR)-γ and their synthetic ligands have direct effects on pancreatic β-cells. We investigated whether PPAR-γ activation stimulates insulin secretion through the up-regulation of GPR40 in β-cells.Rat insulinoma INS-1 cells primary rat islets were treated with rosiglitazone (RGZ) and/or adenoviral overexpression. OLETF rats RGZ.PPAR-γ RGZ overexpression increased free fatty acid (FFA) expression, intracellular calcium...
Peripheral insulin resistance contributes to the development of type 2 diabetes. TCF7L2 has been tightly associated with this disease, although exact mechanism was largely elusive. Here we propose a novel role in hepatic glucose metabolism mammals. Expression medium and short isoforms greatly diminished livers diet-induced genetic mouse models resistance, prompting us delineate functional these metabolism. Knockdown promoted increased blood levels intolerance gluconeogenic gene expression...
Dysregulation of Ca2+/calmodulin-dependent protein kinase (CaMK)II is closely linked with myocardial hypertrophy and heart failure. However, the mechanisms that regulate CaMKII activity are incompletely understood. Here we show arginine methyltransferase 1 (PRMT1) essential for preventing cardiac hyperactivation. Mice null PRMT1 exhibit a rapid progression to dilated cardiomyopathy failure within 2 months, accompanied by cardiomyocyte fibrosis. Consistently, downregulated in patients....
Recent studies have shown that defined factors could lead to the direct conversion of fibroblasts into induced hepatocyte-like cells (iHeps). However, reported efficiencies are very low, and underlying mechanism hepatic reprogramming is largely unknown. Here, we report iHeps a stepwise transition involving erasure somatic memory, mesenchymal-to-epithelial transition, induction cell fate in sequential manner. Through screening for additional potentially enhance kinetics, found c-Myc Klf4 (CK)...