A5079132836- Autophagy in Disease and Therapy
- Telomeres, Telomerase, and Senescence
- Genetics, Aging, and Longevity in Model Organisms
- Circadian rhythm and melatonin
- Immune Response and Inflammation
- Advanced biosensing and bioanalysis techniques
- Endoplasmic Reticulum Stress and Disease
- Antimicrobial Peptides and Activities
- Toxoplasma gondii Research Studies
- RNA Interference and Gene Delivery
- Cancer, Hypoxia, and Metabolism
- Metabolism, Diabetes, and Cancer
- Protease and Inhibitor Mechanisms
- Epigenetics and DNA Methylation
- Plant responses to water stress
- Wnt/β-catenin signaling in development and cancer
- Pancreatic function and diabetes
- Pluripotent Stem Cells Research
- Biosensors and Analytical Detection
- Hippo pathway signaling and YAP/TAZ
- Inflammasome and immune disorders
- Dietary Effects on Health
- Congenital heart defects research
- Alzheimer's disease research and treatments
- Chromosomal and Genetic Variations
Seoul National University
2005-2025
Kyung Hee University
2023
Howard Hughes Medical Institute
2016-2017
Brigham and Women's Hospital
2015-2017
Harvard University
2016-2017
The University of Texas Southwestern Medical Center
2007-2012
Cellular senescence is a terminal stress-activated program controlled by the p53 and p16(INK4a) tumor suppressor proteins. A striking feature of senescence-associated secretory phenotype (SASP), pro-inflammatory response linked to promotion aging. We have identified transcription factor GATA4 as SASP regulator. stabilized in cells undergoing required for SASP. Normally, degraded p62-mediated selective autophagy, but this regulation suppressed during senescence, thereby stabilizing GATA4....
Autophagy is a major pathway used to degrade long-lived proteins and organelles. thought promote both cell organism survival by providing fundamental building blocks maintain energy homeostasis during starvation. Under different conditions, however, autophagy may instead act death through an autophagic distinct from apoptosis. Although several recent papers suggest that plays role in death, it not known whether can cause the of organism. Furthermore, why acts some instances but others poorly...
Environmental pollution is gradually increasing owing to the use of fossil fuels and fossil-derived chemicals. To overcome this issue, research on renewable eco-friendly resources being conducted. Biomass, which can replace fossil-based materials, has advantages high carbon efficiency eco-friendliness. Therefore, we propose an integrated process for producing butyric acid, a precursor biofuel, from white birch. Herein, cellulose converted acid via fermentation. Furfural adipic are produced...
Dynamic changes in cell size are associated with development and pathological conditions, including aging. Although enlargement is a prominent morphological feature of cellular senescence, its functional implications unknown; moreover, how senescent cells maintain their state less understood. Here we show that an extensive remodeling actin cytoskeleton necessary for establishing senescence-associated pro-inflammatory secretory phenotype (SASP). This attributed to balancing act between the...
Autophagy is an evolutionally conserved lysosomal pathway used to degrade and turn over long-lived proteins cytoplasmic organelles. Since autophagy was discovered, it has been thought act as a pro-survival response several stresses, especially starvation, at the cell organism levels by providing recycled metabolic substrates maintain energy homeostasis. However, recent studies suggest that also plays pro-death role through autophagic death mostly cellular level. The mechanism which could...
Abstract Low-density lipoprotein receptor-related protein 6 (LRP6) is a coreceptor of the β-catenin-dependent Wnt signaling pathway. The LRP6 ectodomain binds proteins, as well inhibitors such sclerostin (SOST), which negatively regulates in osteocytes. Although 1 (E1) known to interact with SOST, several unresolved questions remain, reason why SOST E1E2 higher affinity than E1 domain alone. Here, we present crystal structure E1E2–SOST complex two interaction sites tandem. unexpected...
When the supply of environmental nutrients is limited, multicellular animals can make both physiological and behavioral changes so as to cope with nutrient starvation. Although effects starvation are well known, mechanisms by which sense systemically remain elusive. Furthermore, what constituent food sensed how it modulates response still poorly understood. In this study, we use a starvation-hypersensitive mutant identify molecules that modulate signaling. We found specific amino acids could...
Senescence is a terminal differentiation program that halts the growth of damaged cells and must be circumvented for cancer to arise. Here we describe panel genetic screens identify genes required replicative senescence. We uncover role in senescence potent tumor suppressor ATM substrate USP28. USP28 controls activation both TP53 branch GATA4/NFkB senescence-associated secretory phenotype (SASP). These results suggest ubiquitination imply common node downstream from links GATA4 branches response.
UDP-GlcNAc serves as a building block for glycosaminoglycan (GAG) chains in cartilage proteoglycans and simultaneously acts substrate O-GlcNAcylation. Here, we show that transporters to the endoplasmic reticulum (ER) Golgi are significantly downregulated osteoarthritic cartilage, leading increased cytosolic O-GlcNAcylation chondrocytes. Mechanistically, upregulated governs senescence-associated secretory phenotype (SASP) by stabilizing GATA4 via at S406, which compromises its degradation...
Senescence stimuli activate multiple tumor suppressor pathways to initiate cycle arrest and a differentiation program characteristic of senescent cells. We performed two-stage, gain-of-function screen select for the genes whose enhanced expression can bypass replicative senescence. uncovered known be involved in p53 Rb regulation ATM regulation, two components CST (CTC1–STN1–TEN1) complex preventing telomere erosion, such as REST FOXO4 that have been implicated aging. Among new now...
Abstract p62/SQSTM1 is known to act as a key mediator in the selective autophagy of protein aggregates, or aggrephagy, by steering ubiquitinated aggregates towards pathway. Here, we use yeast two-hybrid screen identify prefoldin-like chaperone UXT an interacting p62. We show that can bind well LB domain p62, and, possibly forming oligomer, increase p62 clustering for its efficient targeting thereby promoting formation body and clearance cargo via autophagy. also find ectopic expression human...
The Wnt signaling pathway plays a critical role in the developmental and physiological processes of metazoans. We previously reported that Frizzled4 (FZD4) linker domain an important Norrin binding signaling. However, question remains whether FZD contributes to general. Here, we show is involved affects downstream A FZD4 chimera, which was swapped with non-canonical receptor FZD6, impairs WNT3A suppresses recruitment LRP6 Disheveled, resulting reduced canonical similar effect observed for...
Natural products and their derivatives historically represent alternatives to conventional synthetic molecules for pharmacotherapy, ranging from cancer chemotherapeutics cosmetic ingredients that exert anti-aging activities. Cellular senescence is considered a main driver of skin aging, yet natural target in specific manner are not thoroughly explored. Here, we performed focused compound screen identify anti-senescence effects. We found Isatis tinctoria, woad extracts, displayed senolytic...