A5100330475- Cancer, Hypoxia, and Metabolism
- CRISPR and Genetic Engineering
- Peroxisome Proliferator-Activated Receptors
- Biochemical and Molecular Research
- Metabolism, Diabetes, and Cancer
- Cancer, Lipids, and Metabolism
- HIV Research and Treatment
- Ubiquitin and proteasome pathways
- Immune Cell Function and Interaction
- Pancreatic and Hepatic Oncology Research
- PI3K/AKT/mTOR signaling in cancer
- Lung Cancer Treatments and Mutations
- Cancer-related Molecular Pathways
- Wnt/β-catenin signaling in development and cancer
- Protein Kinase Regulation and GTPase Signaling
- RNA modifications and cancer
- interferon and immune responses
- Cancer Research and Treatments
- Cancer-related gene regulation
- Inflammatory mediators and NSAID effects
- Amino Acid Enzymes and Metabolism
- HIV/AIDS drug development and treatment
- DNA Repair Mechanisms
- T-cell and B-cell Immunology
- Cancer-related molecular mechanisms research
Hunan Normal University
2025
Sichuan University
2016-2025
Shanghai Changzheng Hospital
2022-2025
Research Center for Eco-Environmental Sciences
2025
Chinese Academy of Sciences
2016-2025
West China Hospital of Sichuan University
2022-2025
Hunan Provincial People's Hospital
2020-2025
Shanghai Medical College of Fudan University
2025
Shanghai Cancer Institute
2025
Fudan University Shanghai Cancer Center
2025
The mammalian target of rapamycin complex 1 (mTORC1) integrates mitogen and nutrient signals to control cell proliferation size. Hence, mTORC1 is implicated in a large number human diseases--including diabetes, obesity, heart disease, cancer--that are characterized by aberrant growth proliferation. Although eukaryotic translation initiation factor 4E-binding proteins (4E-BPs) critical mediators function, their precise contribution signaling the mechanisms which they mediate function have...
T-cell receptor (TCR) diversity, a prerequisite for immune system recognition of the universe foreign antigens, is generated in first two decades life thymus and then persists to an unknown extent through via homeostatic proliferation naïve T cells. We have used next-generation sequencing nonparametric statistical analysis estimate lower bound total number different TCR beta (TCRB) sequences human repertoires. arrived at surprisingly high minimal estimates 100 million unique TCRB CD4 CD8...
KRAS gain-of-function mutations occur in approximately 30% of all human cancers. Despite more than 30 years KRAS-focused research and development efforts, no targeted therapy has been discovered for cancers with mutations. Here, we describe ARS-853, a selective, covalent inhibitor KRAS(G12C) that inhibits mutant KRAS-driven signaling by binding to the GDP-bound oncoprotein preventing activation. Based on rates engagement inhibition observed along mutant-specific mass spectrometry-based assay...
Several described growth factors influence the proliferation and regeneration of intestinal epithelium. Using a transgenic mouse model, we identified human gene, R-spondin1, with potent specific proliferative effects on crypt cells. Human R-spondin1 (hRSpo1) is thrombospondin domain-containing protein expressed in enteroendocrine cells as well epithelial various tissues. Upon injection into mice, induced rapid onset cell involving beta-catenin stabilization, possibly by process that distinct...
The functional and therapeutic importance of the Warburg effect is increasingly recognized, glycolysis has become a target anticancer strategies. We recently reported identification group novel small compounds that inhibit basal glucose transport reduce cancer cell growth by deprivation-like mechanism. hypothesized Glut1 are efficacious in vivo as agents. Here, we report representative compound WZB117 not only inhibited lines but also nude mouse model. Daily intraperitoneal injection at 10...
Constitutive overexpression and activation of NPM-ALK fusion protein [t(2:5)(p23;q35)] is a key oncogenic event that drives the survival proliferation anaplastic large-cell lymphomas (ALCLs). We have identified highly potent selective small-molecule ALK inhibitor, NVP-TAE684, which blocked growth ALCL-derived ALK-dependent cell lines with IC(50) values between 2 10 nM. NVP-TAE684 treatment resulted in rapid sustained inhibition phosphorylation its downstream effectors subsequent induction...
Triple-negative breast cancer (TNBC) is an aggressive form of with no effective targeted therapy. Inducible nitric oxide synthase (iNOS) associated poor survival in patients by increasing tumor aggressiveness. This work aimed to investigate the potential iNOS inhibitors as a therapy for TNBC. We hypothesized that inhibition endogenous would decrease TNBC aggressiveness reducing initiation and metastasis through modulation epithelial-mesenchymal transition (EMT)-inducing factors.iNOS protein...
The prime editor (PE) can edit genomes with almost any intended changes, including all 12 possible types of base substitutions, small insertions and deletions, their combinations, without the requirement for double strand breaks or exogenous donor templates. PE demonstrates possibility correcting a variety disease-causing mutations might expand therapeutic application gene editing. In this study, was optimized based on dual-adeno-associated virus (AAV) split-intein system in vitro by...
The R-Spondin (RSpo) family of secreted proteins act as potent activators the Wnt/β-catenin signaling pathway. We have previously shown that RSpo can induce proliferative effects on gastrointestinal epithelium in mice. Here we provide a mechanism whereby RSpo1 regulates cellular responsiveness to Wnt ligands by modulating cell-surface levels coreceptor LRP6. show activity critically depends presence canonical and Although does not directly activate LRP6, it interferes with...
Abstract Active-site mTOR inhibitors (asTORi) hold great promise for targeting dysregulated signaling in cancer. Because of the multifaceted nature mTORC1 signaling, identification reliable biomarkers sensitivity tumors to asTORi is imperative their clinical implementation. Here, we show that cancer cells acquire resistance by downregulating eukaryotic translation initiation factor (eIF4E)-binding proteins (4E-BPs—EIF4EBP1, EIF4EBP2). Loss 4E-BPs or overexpression eIF4E renders neoplastic...
Innate immune system is armed by several lines of pattern recognition receptors to sense various viral infection and initiate antiviral response. This process under a tight control the negative feedback induced and/or inflammation critical maintain homoeostasis prevent autoimmune disorders, however, molecular mechanism not fully understood. Here we report TRIM29, ubiquitin E3 ligase, functions as an inducible regulator innate response triggered DNA virus cytosolic DNA. stimulation induce...
Significance Human B cells secrete highly diverse antibody molecules to recognize and defend against infectious agents. Developing independently rearrange their genomes produce antibody-encoding sequences. It is uncertain what degree genetic factors control repertoires the antibodies elicited by defined antigenic stimuli. Analysis of 134,000 heavy chain sequences from genetically identical twins vaccinated with varicella-zoster vaccine indicates that show increased correlation in gene...
Pancreatic intraepithelial neoplasia (PanIN) is a precursor of pancreatic ductal adenocarcinoma (PDAC), which commonly occurs in the general populations with aging. Although most PanIN lesions (PanINs) harbor oncogenic KRAS mutations that initiate tumorigenesis; PanINs rarely progress to PDAC. Critical factors promote this progression, especially targetable ones, remain poorly defined. We show peroxisome proliferator-activated receptor-delta (PPARδ), lipid nuclear receptor, upregulated...
ABSTRACT Typically during human immunodeficiency virus type 1 (HIV-1) infection, a nearly homogeneous viral population first emerges and then diversifies over time due to selective forces that are poorly understood. To identify these forces, we conducted an intensive longitudinal study of genetic changes T-cell immunity in one subject at ≤17 points his 3 years infecting partner near the transmission. Autologous peptides covering amino acid sites inferred be under positive selection were...
Strength-endurance type of sport can lead to modification human beings' physiological status. The present study aimed investigate the alteration metabolic phenotype or biochemical compositions in professional athletes induced by long-term training means a novel systematic tool, metabolomics. Resting venous blood samples junior and senior male rowers were obtained before after 1-wk 2-wk training. Venous from healthy volunteers as control was also sampled at rest. Endogenous metabolites serum...
HIV-1 transmission and viral evolution in the first year of infection were studied 11 individuals representing four transmitter-recipient pairs three independent seroconverters. Nine these enrolled during acute infection; all men who have sex with (MSM) infected subtype B. A total 475 nearly full-length genome sequences generated, on average 10 genomes per specimen at 2 to 12 visits over infection. Single founding variants homogeneous populations detected eight nine Restriction a single...
The V3 loop of the HIV-1 Env protein is primary determinant viral coreceptor usage, whereas V1V2 region thought to influence binding and participate in shielding neutralization-sensitive regions glycoprotein gp120 from antibody responses. functional properties antigenicity are influenced by changes amino acid sequence, sequence length patterns N-linked glycosylation. However, how these polymorphisms relate HIV pathogenesis not fully understood. We examined 5185 nucleotide fragments clinical...