A5088385164- CRISPR and Genetic Engineering
- Prostate Cancer Treatment and Research
- DNA Repair Mechanisms
- BRCA gene mutations in cancer
- Sexual Differentiation and Disorders
- PARP inhibition in cancer therapy
- Plant Pathogens and Fungal Diseases
- CAR-T cell therapy research
- Mass Spectrometry Techniques and Applications
- Plant Stress Responses and Tolerance
- Photosynthetic Processes and Mechanisms
- Optical Network Technologies
- Radioactive element chemistry and processing
- Melanoma and MAPK Pathways
- Advanced Fiber Optic Sensors
- RNA Interference and Gene Delivery
- Light effects on plants
- Plant and fungal interactions
- Biocrusts and Microbial Ecology
- Metal Extraction and Bioleaching
- Plant-Microbe Interactions and Immunity
- Advanced Photonic Communication Systems
- Tree Root and Stability Studies
- Ubiquitin and proteasome pathways
- Hippo pathway signaling and YAP/TAZ
Memorial Sloan Kettering Cancer Center
2015-2024
Nanchang Hangkong University
2023-2024
Kettering University
2023-2024
Beijing University of Posts and Telecommunications
2017
Germ-line and somatic mutations in genes that promote homology-directed repair (HDR), especially BRCA1 BRCA2, are frequently observed several cancers, particular, breast ovary but also prostate other cancers. HDR is critical for the error-free of DNA double-strand breaks lesions, factors protect stalled replication forks. As a result, loss or BRCA2 poses significant risks to genome integrity, leading not only cancer predisposition sensitivity DNA-damaging agents, affecting therapeutic...
Abstract Mutations in the tumor suppressor BRCA2 predominantly predispose to breast cancer. Paradoxically, while loss of promotes formation, it also causes cell lethality, although how lethality is triggered unclear. Here, we generate conditional non-transformed human mammary epithelial lines using CRISPR-Cas9. Cells are inviable upon loss, which leads replication stress associated with under replication, causing mitotic abnormalities, 53BP1 nuclear body formation ensuing G1 phase, and...
The androgen receptor (AR) is a nuclear that governs gene expression programs required for prostate development and male phenotype maintenance. Advanced cancers display AR hyperactivation transcriptome expansion, in part, through amplification interaction with oncoprotein cofactors. Despite its biological importance, how domains cofactors cooperate to bind DNA has remained elusive. Using single-particle cryo-electron microscopy, we isolated three conformations of bound DNA, showing forms...
BRCA2 is a breast and ovarian tumor suppressor that guards against genome instability, hallmark of cancer. Significant progress has been made in improving our understanding function from biochemical, cellular, mouse studies. The knowledge gained actively exploited to develop therapeutic strategies, including PARP inhibition, which shown promising clinical outcomes. Recently, tremendous excitement generated by the findings roles other proteins suppressing replication stress through homologous...
Gene editing techniques have been extensively used to attempt model recurrent genomic rearrangements found in tumor cells. These methods involve the induction of double-strand breaks at endogenous loci followed by identification breakpoint junctions within a population, which typically arise nonhomologous end joining. The low frequency these events, however, has hindered cloning cells with desired rearrangement before oncogenic transformation. Here we present strategy combining CRISPR-Cas9...
Significance Modeling cancer formation requires introduction of relevant oncogenic perturbations into normal cells in a tissue/cell-type–specific manner. Genetically engineered mouse models are powerful but require significant time and cost to generate maintain. The ability edit primary epithelial ex vivo followed by orthotopic transplantation provides an alternative strategy for modeling efficient gene editing, typically multiplex fashion. Here we successfully engineer multigenic or...
Changes in FOXA1 (forkhead box protein A1) levels are well associated with prostate cancer (PCa) progression. Unfortunately, direct targeting of progressive PCa remains challenging due to variations levels, increased mutations at different stages PCa, and elusive post‐translational regulating mechanisms. Here, we show that SKP2 (S‐phase kinase‐associated 2) catalyzes K6‐ K29‐linked polyubiquitination for lysosomal‐dependent degradation. Our data indicate SKP2:FOXA1 ratios stage IV human...
Abstract Translocations of the ETS family transcription factor ERG are found in nearly 150,000 newly diagnosed prostate cancers (PCas) each year United States underscoring importance defining mechanism by which promotes epithelial transformation. A consequence all translocations is aberrant expression luminal cells under transcriptional control TMPRSS2. Multiple lines evidence implicate as an initiating event cancer. seen prostatic intraepithelial neoplasia (PIN) and proliferative...
To gain insight into how ERG translocations cause prostate cancer, we performed single cell transcriptional profiling of an autochthonous mouse model at early stage disease initiation. Despite broad expression in all epithelial cells, proliferation was enriched a small, stem-like population with mixed-luminal basal identity (called intermediate cells). Through series lineage tracing and primary tissue transplantation experiments, find that tumor initiating activity resides subpopulation...
This paper proposes a light intensity monitoring method using FBG-based fiber optic sensor. The simulation results show that there is linear relationship between the and wavelength shift of FBG.
Abstract BRCA2 deficiency causes genome instability and breast ovarian cancer predisposition, but also paradoxically promotes cell lethality. The nature of the acute, detrimental consequences loss is not fully understood. We recently generated conditional models from a non-transformed human mammary line, through allele-specific gene targeting using CRISPR-Cas9, which we now describe. With these models, discovered that triggers DNA under replication-53BP1 nuclear body formation-G1 arrest axis...
Summary The androgen receptor (AR) is a steroid and master transcription factor that governs gene expression programs required for luminal development of prostate epithelium, formation muscle tissue maintenance the male phenotype. AR misregulation hallmark multiple malignancies, including cancer, where hyperactivation expansion its transcriptome occur in part through amplification interaction with oncoprotein cofactors. Despite biological importance, how AR’s individual domains protein...
Abstract TMPRSS2-ERG translocations are initiating lesions in nearly 50% of human prostate adenocarcinomas, often conjunction with PTEN loss. In mice, prostate-specific expression ERG using a Probasin-Cre driver (Pb-Cre4) is sufficient to induce invasive Ck8+ luminal adenocarcinoma high penetrance the context Pten Because TMPRSS2 androgen-regulated and thereby largely restricted epithelial cells, it has been assumed that cells likely cell origin for positive cancers. To gain further support...
Endophytes can assist crops in adapting to high temperatures and drought conditions, thereby reducing agricultural losses. However, the mechanism through which endophytes regulate crop resistance stress remains unclear, concerns regarding safety stability exist with active endophytes. Thus, heat-treated endophytic bacteria LSE01 (HTB) were employed as a novel microbial fertilizer investigate their effects on plant adaptation conditions. The results indicated that diameter weight of tomatoes...