A5101703007- Cancer-related gene regulation
- Lung Cancer Treatments and Mutations
- Epigenetics and DNA Methylation
- Hepatitis B Virus Studies
- RNA and protein synthesis mechanisms
- DNA Repair Mechanisms
- Genetic factors in colorectal cancer
- Mechanisms of cancer metastasis
- Genomics and Chromatin Dynamics
- Liver Disease Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Advanced biosensing and bioanalysis techniques
- RNA Research and Splicing
- RNA modifications and cancer
- Colorectal and Anal Carcinomas
- Cancer-related Molecular Pathways
- Signaling Pathways in Disease
- Estrogen and related hormone effects
- Cancer therapeutics and mechanisms
- Gastric Cancer Management and Outcomes
- Lung Cancer Diagnosis and Treatment
- Gastrointestinal Tumor Research and Treatment
- HER2/EGFR in Cancer Research
- Cancer Genomics and Diagnostics
- Hepatitis C virus research
Tsinghua University
2017-2023
State Key Laboratory of Molecular Oncology
2023
National Institute of Biological Sciences, Beijing
2012-2023
Center for Life Sciences
2021-2022
AstraZeneca (United States)
2020
Herein we report the optimization of a series tricyclic indazoles as selective estrogen receptor degraders (SERD) and antagonists for treatment ER+ breast cancer. Structure based design together with systematic investigation each region molecular architecture led to identification N-[1-(3-fluoropropyl)azetidin-3-yl]-6-[(6S,8R)-8-methyl-7-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-3H-pyrazolo[4,3-f]isoquinolin-6-yl]pyridin-3-amine (28). This compound was demonstrated be highly potent SERD that...
Abstract Metabolic reprogramming evolves during cancer initiation and progression. However, thorough understanding of metabolic evolution from preneoplasia to lung adenocarcinoma (LUAD) is still limited. Here, we perform large-scale targeted metabolomics on resected lesions plasma obtained invasive LUAD its precursors, decipher the trajectories atypical adenomatous hyperplasia (AAH) in situ (AIS), minimally (MIA) (IAC), revealing that perturbed pathways emerge early premalignant lesions....
Abstract Background Sintilimab blocks the interaction between programmed death-1 (PD-1) and its ligands. The safety efficacy of sintilimab combined with oxaliplatin/capecitabine (CapeOx) as first-line treatment were evaluated in patients gastric (G)/gastroesophageal junction (GEJ) adenocarcinoma a phase Ib clinical trial. Methods Patients locally advanced or metastatic G/GEJ without previous systemic enrolled one cohort multi-cohort study. was administered at dose 200 mg intravenously (IV)...
Abstract Background Treatment options for Chinese patients with locally advanced or metastatic squamous‐cell non‐small‐cell lung cancer (sqNSCLC) after failure of first‐line chemotherapy are limited. This study (ORIENT‐3) aimed to evaluate the efficacy and safety sintilimab versus docetaxel as second‐line treatment in sqNSCLC. Methods ORIENT‐3 was an open‐label, multicenter, randomized controlled phase 3 trial that recruited stage IIIB/IIIC/IV sqNSCLC platinum‐based chemotherapy. Patients...
Abstract Molecular interplay between host epigenetic factors and viral proteins constitutes an intriguing mechanism for sustaining hepatitis B virus (HBV) life cycle its chronic infection. HBV encodes a regulatory protein, HBx, which activates transcription replication of genome organized as covalently closed circular (ccc) DNA minichromosome. Here we illustrate how HBx accomplishes task by hijacking Spindlin1, reader comprising three consecutive Tudor domains. Our biochemical structural...
The PAF1 complex (PAF1C) functions in multiple transcriptional processes involving RNA polymerase II (RNA Pol II). Enhancer RNAs (eRNAs) and promoter upstream transcripts (PROMPTs) are pervasive transcribed by degraded rapidly the nuclear exosome after 3' endonucleolytic cleavage Integrator (Integrator). Here we show that PAF1C has a role termination of eRNAs PROMPTs cleaved 1-3 kb downstream transcription start site. Mechanistically, facilitates recruitment to sites transcript cleavage,...
ABSTRACT Spindlin1 is a transcriptional coactivator with three Tudor-like domains, of which the first and second Tudors are engaged in histone methylation readout, while function third Tudor largely unknown. Recent studies revealed that co-activator activity could be attenuated by SPIN•DOC. Here we solved crystal structure SPIN•DOC-Spindlin1 complex, revealing hydrophobic motif, DOCpep3 (256-281), SPIN•DOC interacts 3 completes its β-barrel fold. Massive contacts hydrogen bonding...
Proliferating cell nuclear antigen (PCNA), a ring‐shaped homotrimer, is an essential factor in DNA metabolism including replication and repair. PCNA functions these reactions appear to be regulated by posttranslational modifications, such as ubiquitylation, sumoylation phosphorylation . Recently, we have shown that EGFR at tyrosine 211 (Y211) disrupts interactions with mismatch recognition proteins, thereby inhibiting repair (MMR). In addition, phosphorylated promotes misincorporation during...
Abstract Molecular interplay between host epigenetic factors and viral proteins constitutes an intriguing mechanism in sustaining hepatitis B virus (HBV) life cycle its chronic infection. HBV encodes a regulatory protein, HBx, which activates transcription replication of genome organized as covalently closed circular (ccc) DNA minichromosome. Here we illustrate how HBx accomplishes task by hijacking Spindlin1, reader comprising three consecutive Tudor domains. Our biochemical structural...