A5049759564- Epigenetics and DNA Methylation
- Cholesterol and Lipid Metabolism
- Cancer-related gene regulation
- RNA modifications and cancer
- Adipose Tissue and Metabolism
- Lipid metabolism and biosynthesis
- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
- Ubiquitin and proteasome pathways
- Hepatitis C virus research
- interferon and immune responses
- Hepatitis B Virus Studies
- MicroRNA in disease regulation
- Cancer, Lipids, and Metabolism
- Endoplasmic Reticulum Stress and Disease
- Glycosylation and Glycoproteins Research
- Pancreatic function and diabetes
- Liver Disease Diagnosis and Treatment
- Lipoproteins and Cardiovascular Health
- Peroxisome Proliferator-Activated Receptors
- Caveolin-1 and cellular processes
- Drug Transport and Resistance Mechanisms
- CAR-T cell therapy research
- Ferroptosis and cancer prognosis
- Synthetic Organic Chemistry Methods
Beijing Aerospace General Hospital
2025
ShanghaiTech University
2018-2024
Southern Medical University
2016-2024
Nanfang Hospital
2016-2024
Macau University of Science and Technology
2024
Kunming University of Science and Technology
2024
Shanghai Clinical Research Center
2024
Jilin University
2013-2023
Anhui Medical University
2023
Third People's Hospital of Hefei
2023
Ezh2 (Enhancer of zeste homolog 2) protein is the enzymatic component Polycomb repressive complex 2 (PRC2), which represses gene expression by methylating lysine 27 histone H3 (H3K27) and regulates cell proliferation differentiation during embryonic development. Recently, hot-spot mutations were identified in diffused large B-cell lymphomas follicular lymphomas. To investigate if tumor growth dependent on activity Ezh2, we developed a potent selective small molecule inhibitor, EI1, inhibits...
Cuproptosis and ferroptosis are the two newly defined metal-related regulated cell death. However, crosstalk between cuproptosis is obscure.We analyzed effect of inducers on copper ionophores-induced death through CCK-8 assay. was studied using immunofluorescence protein soluble-insoluble fraction isolation. GSH assay, qRT-PCR western blot were adopted to explore machinery enhanced cuproptosis. And mouse xenograft model built detect synergy elesclomol-Cu sorafenib in vivo.Herein we found...
The remarkable action of an IIII species on a tripeptide containing acyclic tyrosine/tryptophan is the key step in total synthesis (−)-diazonamide A. completed preparation this new antimitotic concise, multiply convergent, and amenable to diversification intermediates.
Dietary absorption is a major way for mammals to obtain cholesterol, which mediated by Niemann-Pick C1-like 1 (NPC1L1) via vesicular endocytosis. One fundamental question in this process how free cholesterol efficiently taken up through the internalization of NPC1L1. Using exogenously expressed NPC1L1-EGFP, we show that lipid raft proteins flotillins associate with NPC1L1 and their localization regulated during intracellular trafficking. Furthermore, are essential NPC1L1-mediated cellular...
Statins are inhibitors of HMG-CoA reductase, the rate-limiting enzyme cholesterol biosynthesis, and have been clinically used to treat cardiovascular disease. However, a paradoxical increase reductase protein following statin treatment may attenuate effect side effects. Here we present previously unexplored strategy alleviate statin-induced accumulation by inducing its degradation. Inspired observations that intermediates trigger degradation, identify potent degrader, namely Cmpd 81, through...
The histone methyltransferase Enhancer of Zeste Homolog 2 (EZH2) is frequently dysregulated in cancers, and gain-of-function (GOF) EZH2 mutations have been identified non-Hodgkin lymphomas. Small-molecule inhibitors against demonstrated anti-tumor activity EZH2-mutated lymphomas entered clinical trials. Here, we developed models acquired resistance to inhibitor EI1 with lymphoma cells. Resistance was generated by secondary both wild-type (WT) GOF Y641N alleles. These mutants retained the...
A missing link in cholesterol absorption Cholesterol is important for general health, but too much can build up artery walls and cause cardiovascular disease. Low-density lipoprotein (LDL-C) often referred to as “bad cholesterol”; keeping LDL-C within stringent limits recommended reduce the risk of heart attack stroke. Zhang et al. discovered that some individuals have an inherited frameshift mutation LIMA1 gene (also known EPLIN or SREBP3 ). The has not been linked lipid metabolism before,...
Overexpression and somatic heterozygous mutations of EZH2, the catalytic subunit polycomb repressive complex 2 (PRC2), are associated with several tumor types. EZH2 inhibitor, EPZ-6438 (tazemetostat), demonstrated clinical efficacy in patients acceptable safety profile as monotherapy. EED, another PRC2 complex, is essential for its histone methyltransferase activity through direct binding to trimethylated lysine 27 on 3 (H3K27Me3). Herein we disclose discovery a first-in-class potent,...
Polycomb Repressive Complex 2 (PRC2) plays an important role in transcriptional regulation during animal development and cell differentiation, alteration of PRC2 activity has been associated with cancer. On a molecular level, catalyzes methylation histone H3 lysine 27 (H3K27), resulting mono-, di-, or trimethylated forms H3K27, which the form H3K27me3 leads to repression polycomb target genes. Previously, we have shown that binding low-molecular-weight compound EED226 pocket regulatory...
Abstract Background and Aims NASH is associated with high levels of cholesterol triglyceride (TG) in the liver; however, there still no approved pharmacological therapy. Synthesis TG controlled by sterol regulatory element‐binding protein (SREBP), which found to be abnormally activated patients. We aim discover small molecules for treating inhibiting SREBP pathway. Approach Results Here, we identify a potent inhibitor, 25‐hydroxylanosterol (25‐HL). 25‐HL binds insulin‐induced gene (INSIG)...
Women with perinatal depression and their children are at increased risk of poor health outcomes. Integrating evidence based non-stigmatizing interventions within existing systems is crucial to reducing psychosocial distress during pregnancy preventing depression. This study aimed evaluate the feasibility World Health Organization (WHO) endorsed cognitive-behavior therapy-based Thinking Healthy Programme (THP), delivered by antenatal nurses in China. A two-arm pilot randomized controlled...
Polo-like kinase 1 (Plk1) is required for the generation of tension-sensing 3F3/2 kinetochore epitope and facilitates localization Mad2 other spindle checkpoint proteins. Here, we investigate mechanism by which Plk1 itself recruited to kinetochores. We show that binds budding uninhibited benzimidazole (Bub1) in mitotic human cells. The Plk1-Bub1 interaction requires polo-box domain (PBD) enhanced cyclin-dependent (Cdk1)-mediated phosphorylation Bub1 at T609. PBD-dependent binding vitro....
Niemann-Pick C1-like 1 (NPC1L1) is a multitransmembrane protein playing crucial role in dietary and biliary cholesterol absorption. Cholesterol promotes the formation endocytosis of NPC1L1-flotillin-cholesterol membrane microdomains, which an early step uptake. How sensed this unknown. Here, we find that N-terminal domain (NTD) NPC1L1 binds cholesterol. Mutation residue Leu-216 NPC1L1-NTD eliminates binding, decreases prevents NPC1L1-mediated uptake culture cells mice livers. specifically...