A5072547453- Autophagy in Disease and Therapy
- PI3K/AKT/mTOR signaling in cancer
- Endoplasmic Reticulum Stress and Disease
- Mesenchymal stem cell research
- Cannabis and Cannabinoid Research
- Liver Disease Diagnosis and Treatment
- Adipose Tissue and Metabolism
- Pancreatic function and diabetes
- Mycobacterium research and diagnosis
- Lipid metabolism and biosynthesis
- Lanthanide and Transition Metal Complexes
- Hippo pathway signaling and YAP/TAZ
- Neurogenesis and neuroplasticity mechanisms
- Pharmacological Effects of Natural Compounds
- Spinal Cord Injury Research
- Nerve injury and regeneration
- Sirtuins and Resveratrol in Medicine
- Protein Kinase Regulation and GTPase Signaling
- Lysosomal Storage Disorders Research
- Cancer Mechanisms and Therapy
- Ubiquitin and proteasome pathways
- Inflammasome and immune disorders
- Reproductive System and Pregnancy
- Tuberculosis Research and Epidemiology
- Angiogenesis and VEGF in Cancer
Konyang University
2016-2025
Konyang University Hospital
2025
Seoul National University Dental Hospital
2022
Seoul National University
2009-2021
University of Michigan
2012-2020
Smith-Kettlewell Eye Research Institute
2016
Ann Arbor Center for Independent Living
2013-2015
Daejeon University
2014-2015
Autophagy deregulation during obesity contributes to the pathogenesis of diverse metabolic disorders. However, without understanding molecular mechanism interference in autophagy, development therapeutic strategies for correcting such defects obese individuals is challenging. Here we show that a chronic increase cytosolic calcium concentration hepatocytes and lipotoxicity attenuates autophagic flux by preventing fusion between autophagosomes lysosomes. As pharmacological approach restore...
Abstract Sestrins are stress-inducible metabolic regulators that suppress a wide range of age- and obesity-associated pathologies, many which due to mTORC1 overactivation. Upon various stresses, the inhibit activity through an indirect mechanism is still unclear. GATORs recently identified protein complexes regulate RagB, small GTPase essential for activation. GATOR1 activating (GAP) RagB whereas GATOR2 functions as inhibitor GATOR1. However, how physiologically regulated unknown. Here we...
Autophagy is a homeostatic process that important for degrading protein aggregates, nutrient deposits, dysfunctional organelles and several signaling molecules. p62/sequestosome‐1 binds to autophagy substrates, such as ubiquitinated proteins, damaged mitochondria molecules an Nrf2 inhibitor Keap1, promoting their autophagic degradation. Sestrin2, stress‐inducible protein, has recently been shown bind p62 promote degradation of targets. Because Sestrin2 metabolic regulator suppresses diverse...
Obesity commonly leads to hepatic steatosis, which often provokes lipotoxic injuries hepatocytes that cause nonalcoholic steatohepatitis (NASH). NASH, in turn, is associated with the accumulation of insoluble protein aggregates are composed ubiquitinated proteins and ubiquitin adaptor p62/sequestosome 1 (SQSTM1). Formation p62 inclusions critical marker distinguishes simple fatty liver from NASH predicts a poor prognostic outcome for subsequent carcinogenesis. However, molecular mechanism by...
Emerging evidence indicates that aberrant maternal inflammation is associated with several pregnancy-related disorders such as preeclampsia, preterm birth, and intrauterine growth restriction. Sirtuin1 (SIRT1), a class III histone deacetylase, involved in the regulation of various physiopathological processes including cellular metabolism. However, effect SIRT1 on placental proinflammatory environment remains to be elucidated. In this study, we investigated lipopolysaccharide (LPS)-induced...
Abstract Chronic exposure to bile acid in the liver due impaired flow induces cholestatic disease, resulting hepatotoxicity and fibrosis. Sestrin2, a highly conserved, stress-inducible protein, has been implicated cellular responses multiple stress conditions maintenance of homeostasis. However, its role injury is not fully understood. In this study, we investigated hepatic Sestrin2 underlying mechanisms using vivo vitro approaches. Hepatic expression was upregulated by activating...
Abstract Human bone marrow‐derived mesenchymal stem cells (hMSCs) are considered a desirable cell source for autologous transplantation therapy to treat nervous system injury due their ability differentiate into specific types and render the tissue microenvironment more favorable repair by secreting various growth factors. To potentiate possible trophic effect, hMSCs were induced without genetic modification adopt characteristics of Schwann (SCs), which provide support regenerating axons....
The mTOR complex 1 (mTORC1) and endoplasmic reticulum (ER) stress pathways are critical regulators of intestinal inflammation colon cancer growth. Sestrins stress-inducible proteins, which suppress both mTORC1 ER stress; however, the role in physiology tumorigenesis has been elusive due to lack studies human tissues or appropriate animal models. In this study, we show that SESN2 expression is elevated ulcerative colitis patients but lost upon p53 inactivation during carcinogenesis. mouse...
Significance Antioxidant therapy was once considered useful for treating metabolic syndrome because excessive accumulation of reactive oxygen species (ROS) identified as an inducer diverse pathologies. However, the effectiveness dietary antioxidants in obesity-associated diseases had been largely controversial numerous animal and human clinical studies, some which actually show adverse effects upon antioxidant consumption. Here, we that Sestrin2 other can interfere with uncoupling protein 1...
Rationale: Dimethyl sulfoxide (DMSO) is commonly used as a solvent for water-insoluble substances, vehicle drug therapy, and cryoprotectant cultured cells. DMSO induced embryonic defects its mechanism of action remains unclear. The rationale based on the assumption that supplementation should induce long-term negative effects both pre- post-implantation embryo development. Methods: oxidative stress, ER autophagy, mitophagy, signaling responsible genes proteins were determined by RT-qPCR,...
Sestrins represent a family of stress-inducible proteins that prevent the progression many age- and obesity-associated disorders. Endogenous maintain insulin-dependent AKT Ser/Thr kinase (AKT) activation during high-fat diet–induced obesity, overexpressed activate in various cell types, including liver skeletal muscle cells. Although Sestrin-mediated improves metabolic parameters, mechanistic details underlying such improvement remain elusive. Here, we investigated how Sestrin2, Sestrin...
Mycobacterium abscessus (Mab), a nontuberculous mycobacterium, is increasing in prevalence worldwide and causes treatment-refractory pulmonary diseases. However, how Mab rewires macrophage energy metabolism to facilitate its survival poorly understood. We compared the metabolic profiles of murine bone marrow-derived macrophages (BMDMs) infected with smooth (S)- rough (R)-type using extracellular flux technology. infection shifted BMDMs towards more energetic phenotype, marked by increased...
Autophagy-related 1 (Atg1)/Unc-51-like protein kinases (ULKs) are evolutionarily conserved proteins that play critical physiological roles in controlling autophagy, cell growth and neurodevelopment. RB1-inducible coiled-coil (RB1CC1), also known as PTK2/FAK family-interacting of 200 kDa (FIP200) is a recently discovered binding partner ULK1. Here we isolated the Drosophila RB1CC1/FIP200 homolog (Fip200/CG1347) showed it mediates Atg1-induced autophagy genetically downstream component diverse...
Autophagy is an essential process for eliminating ubiquitinated protein aggregates and dysfunctional organelles. Defective autophagy associated with various degenerative diseases such as Parkinson disease. Through a genetic screening in Drosophila, we identified CG11148, whose product orthologous to GIGYF1 (GRB10-interacting GYF 1) GIGYF2 mammals, new regulator; hereafter refer this gene Gyf. Silencing of Gyf completely suppressed the effect Atg1-Atg13 activation stimulating autophagic flux...
Cell replacement using stem cells is a promising therapeutic approach to treat degenerative motor neuron (MN) disorders, such as amyotrophic lateral sclerosis and spinal cord injury. Human bone marrow-derived mesenchymal (hMSCs) are desirable cell source for autologous therapy nervous system injury due their plasticity, low immunogenicity, lower risk of tumor formation than embryonic cells. However, hMSCs inefficient with regards differentiating into MN-like To solve this limitation, we...
Human bone marrow-derived mesenchymal stem cells (hMSCs) are advantageous for cell-based therapy to treat ischemic diseases owing their capacity secrete various paracrine factors with potent angiogenic activity.In this study, we describe a method increase secreted levels of VEGF and HGF from hMSCs without genetic modification.We demonstrated that transplantation primed into limbs led significantly greater improvements in tissue perfusion limb salvage by increasing capillary formation...
Pathological maternal inflammation and abnormal placentation contribute to several pregnancy-related disorders, including preterm birth, intrauterine growth restriction, preeclampsia. TANK-binding kinase 1 (TBK1), a serine/threonine kinase, has been implicated in the regulation of various physiological processes, innate immune response, autophagy, cell growth. However, relevance TBK1 placental pro-inflammatory environment not investigated. In this study, we assessed effect inhibition on...
Ulcerative colitis is a complex inflammatory bowel disorder disease that can induce rectal and colonic dysfunction. Although the prevalence of IBD in Western countries almost 0.5% general population, genetic causes are still not fully understood. In recent discovery, itaconate was found to function as an immune-modulating metabolite mammalian immune cells, wherein it synthesized antimicrobial compound from citric acid cycle intermediate cis-aconitic acid. However, association between Acod1...