A5100457751- Dermatology and Skin Diseases
- SARS-CoV-2 and COVID-19 Research
- DNA Repair Mechanisms
- COVID-19 Clinical Research Studies
- Adrenal Hormones and Disorders
- Urticaria and Related Conditions
- Allergic Rhinitis and Sensitization
- CRISPR and Genetic Engineering
- Food Allergy and Anaphylaxis Research
- Bioinformatics and Genomic Networks
- Cancer therapeutics and mechanisms
- Asthma and respiratory diseases
- IL-33, ST2, and ILC Pathways
- Cancer-related Molecular Pathways
- Transgenic Plants and Applications
- Metabolism, Diabetes, and Cancer
- interferon and immune responses
- SARS-CoV-2 detection and testing
- Polyomavirus and related diseases
- RNA modifications and cancer
- Animal Virus Infections Studies
- Ubiquitin and proteasome pathways
- Microtubule and mitosis dynamics
- Viral gastroenteritis research and epidemiology
- PARP inhibition in cancer therapy
The University of Texas MD Anderson Cancer Center
2016-2024
Regeneron (United States)
2019-2024
University of Jinan
2024
Institute of Process Engineering
2024
First Affiliated Hospital Zhejiang University
2024
Guangzhou Medical University
2023
National Institutes for Food and Drug Control
2011-2023
Wuhan University
2020-2023
Renmin Hospital of Wuhan University
2020-2023
First Affiliated Hospital of Guangzhou Medical University
2023
A vaccine against COVID-19 is urgently needed for older adults, in whom morbidity and mortality due to the disease are increased. We aimed assess safety, tolerability, immunogenicity of a candidate vaccine, CoronaVac, containing inactivated SARS-CoV-2, adults aged 60 years older.We did randomised, double-blind, placebo-controlled, phase 1/2 clinical trial CoronaVac healthy Renqiu (Hebei, China). Vaccine or placebo was given by intramuscular injection two doses (days 0 28). Phase 1 comprised...
Abstract Inactivating TP53 mutations leads to a loss of function p53, but can also often result in oncogenic gain-of-function (GOF) mutant p53 (mutp53) proteins which promotes tumor development and progression. The GOF activities are well documented, the mechanisms involved remain poorly understood. Here, we study mutp53 interactome find that by targeting minichromosome maintenance complex components (MCMs), predisposes cells replication stress chromosomal instability (CIN), leading...
ABSTRACT BACKGROUND The top priority for the control of COVID-19 pandemic currently is development a vaccine. A phase 2 trial conducted to further evaluate immunogenicity and safety SARS-CoV-2 inactivated vaccine (CoronaVac). METHODS We randomized, double-blind, placebo-controlled optimal dose, CoronaVac. total 600 healthy adults aged 18-59 years were randomly assigned receive injections at dose 3 μg/0.5 mL or 6 μg /0.5mL, placebo on Day 0,14 schedule 0,28 schedule. For evaluation, solicited...
Ferroptosis has been recognized as a unique cell death modality driven by excessive lipid peroxidation and unbalanced cellular metabolism. In this study, we established protein interaction landscape for ferroptosis pathways through proteomic analyses, identified choline/ethanolamine phosphotransferase 1 (CEPT1) lysophosphatidylcholine acyltransferase 3 (LPCAT3)-interacting that regulates LPCAT3 stability. contrast to its known role in promoting phospholipid synthesis, showed CEPT1 suppresses...
Lichenification, common in moderate to severe atopic dermatitis (AD) at any age, is often difficult treat. This analysis assessed dupilumab vs placebo AD lichenification by age and race-defined groups. post hoc included pooled data from five clinical trials of (NCT03054428, NCT03345914, NCT02277743, NCT02277769, NCT02395133), including 1,997 patients aged 6 88 years all races with AD. Placebo/dupilumab randomized groups analyzed (n=1,535) 123/244 children, 85/166 adolescents, 460/457 adults;...
Abstract AMP-activated protein kinase (AMPK) is a key regulator of cellular energy homeostasis. Although AMPK has been studied extensively in processes, understanding its substrates and downstream functional network, their contributions to cell fate disease development, remains incomplete. To elucidate the AMPK-dependent signaling pathways, we performed global quantitative phosphoproteomic analysis using wild-type AMPKα1/α2-double knockout cells discovered 160 phosphorylation sites. Further...
The LKB1/AMPK pathway plays a major role in cellular homeostasis and tumor suppression. Down-regulation of occurs several human cancers has been implicated metabolic diseases. However, the precise upstream regulation LKB1-AMPK is largely unknown. Here, we report that AMPK activation by LKB1 regulated tankyrases. Tankyrases interact with ribosylate LKB1, promoting its K63-linked ubiquitination an E3 ligase RNF146, which blocks LKB1/STRAD/MO25 complex formation activation. tankyrase inhibitors...
Abstract Anticancer drugs, such as camptothecin (CPT), trap topoisomerase I (TOP1) on DNA and form TOP1 cleavage complexes (TOP1cc). Alternative repair pathways have been suggested in the of TOP1cc. However, how these work with TDP1, a key enzyme that specifically hydrolyze covalent bond between catalytic tyrosine 3’-end contribute to TOP1cc is poorly understood. Here, using unbiased whole-genome CRISPR screens generation co-deficient cells TDP1 other genes, we demonstrate MUS81 an important...
Exploiting cancer vulnerabilities is critical for the discovery of anticancer drugs. However, tumor suppressors cannot be directly targeted because their loss function. To uncover specific cells with deficiency in any given suppressor(s), we performed genome-scale CRISPR loss-of-function screens using a panel isogenic knockout generated 12 common suppressors. Here, provide comprehensive and comparative dataset genetic interactions between whole-genome protein-coding genes suppressor genes,...
Eukaryotic cells use copious measures to ensure accurate duplication of the genome. Various genotoxic agents pose threats ongoing replication fork that, if not efficiently dealt with, can result in collapse. It is unknown how precisely controlled and regulated under different conditions. Here, we examined complexity composition upon DNA damage by using a PCNA-based proteomic screen uncover known unexplored players involved stress response. We used camptothecin or UV radiation, which lead...
In young children, atopic dermatitis (AD) imposes a multidimensional burden on many aspects of their quality life (QoL) and that families. LIBERTY AD PRESCHOOL part B was randomized, double- blinded, placebo-controlled phase 3 trial in 162 children (aged 6 months to 5 years) with moderate-to- severe receiving dupilumab or placebo, plus low-potency topical corticosteroids. Post hoc analyses were performed the full analysis set (FAS) subset patients Investigator’s Global Assessment score >...
Cell surface proteins play essential roles in various biological processes and are highly related to cancer development. They also serve as important markers for cell identity targets pharmacological intervention. Despite their great potentials biomedical research, comprehensive functional analysis of remains scarce. Here, with a de novo designed library targeting proteins, we performed vivo CRISPR screens evaluate the effects on tumor survival proliferation. We found that Kirrel1 loss...
The mismatch repair (MMR) family is a highly conserved group of proteins that function in correcting base–base and insertion–deletion mismatches generated during DNA replication. Disruption this process results characteristic microsatellite instability (MSI), defects, susceptibility to cancer. However, significant fraction MSI-positive cancers express MMR genes at normal levels do not carry detectable mutation known genes, suggesting additional factors and/or mechanisms may exist explain...
Abstract Background The management of critically ill patients with coronavirus disease 2019 (COVID‐19), caused by a new human virus severe acute respiratory syndrome 2 (SARS‐CoV‐2), is challenging. Recently, there have been several reports inconsistent results after treatment convalescent plasma (CP) on COVID‐19, which was produced neutralizing antibody titer and tested in P3 or P4 laboratory. However, due to the limitation conditions mass production plasma, most producers hardly had...
Replication timing regulatory factor 1 (RIF1) acts downstream of p53-binding protein 53BP1 to inhibit the resection DNA broken ends, which plays critical roles in determining double-strand break repair pathway choice between nonhomologous end joining and homologous recombination (HR). However, mechanism by this is made not yet clear. In study, we identified that histone chaperone ASF1 associates with RIF1 regulates RIF1-dependent functions damage response. Similar loss RIF1, found resulted...
Type II topoisomerases (TOP2) form transient TOP2 cleavage complexes (TOP2ccs) during their catalytic cycle to relieve topological stress. TOP2ccs are covalently linked TOP2-DNA intermediates that reversible but can be trapped by poisons. Trapped block transactions on DNA and generate genotoxic stress, which the mechanisms of action How cells avoid TOP2cc accumulation remains largely unknown. In this study, we uncovered RAD54 like 2 (RAD54L2) as a key factor mediates TOP2-specific damage...
Immune evasion is not only critical for tumor initiation and progression, but also determines the efficacy of immunotherapies. Through iterative in vivo CRISPR screens with seven syngeneic models, we identified core context-dependent immune pathways across cancer types. This valuable high-confidence dataset available further understanding intrinsic immunomodulators, which may lead to discovery effective anticancer therapeutic targets. With a focus on triple-negative breast (TNBC), found that...
ABSTRACT Host-virus protein-protein interaction is the key component of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lifecycle. We conducted a comprehensive interactome study between virus and host cells using tandem affinity purification proximity labeling strategies identified 437 human proteins as high-confidence interacting proteins. Functional characterization further validation these interactions elucidated how distinct SARS-CoV-2 viral participate in its lifecycle,...
Serologic tests for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) provide information on past infection and immune response. To better understand the persistence of response proportion population who can develop one, authors assessed patterns immunoglobulin G (IgG) positivity over time in individuals tested SARS-CoV-2 RNA or IgG at a large national reference laboratory. More than 2.4 million serology (initiated April 21, 2020) 6.6 nucleic acid amplification testing (NAAT)...
Poly (ADP-ribose) polymerase inhibitor (PARPi)-based therapies initially reduce tumor burden but eventually lead to acquired resistance in cancer patients with BRCA1 or BRCA2 mutation. To understand the potential PARPi mechanisms, we performed whole-genome CRISPR screens discover genetic alterations that change gene essentiality cells inducible depletion of BRCA2. We identified several RNA Polymerase II transcription Mediator complex components, especially Cyclin C (CCNC) as synthetic...