A5081647581- Acute Myeloid Leukemia Research
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Pluripotent Stem Cells Research
- Protein Degradation and Inhibitors
- Reproductive Biology and Fertility
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- DNA Repair Mechanisms
- Sperm and Testicular Function
- Cancer, Hypoxia, and Metabolism
- Hippo pathway signaling and YAP/TAZ
- Cancer Cells and Metastasis
- Coconut Research and Applications
- Fibroblast Growth Factor Research
- Histone Deacetylase Inhibitors Research
- Microtubule and mitosis dynamics
- CRISPR and Genetic Engineering
- Cell death mechanisms and regulation
- MicroRNA in disease regulation
- Immune Cell Function and Interaction
- Lymphoma Diagnosis and Treatment
- FOXO transcription factor regulation
- Advances in Cucurbitaceae Research
Pennsylvania State University
2018-2025
Penn State Milton S. Hershey Medical Center
2018-2025
Chinese Academy of Sciences
2025
Zhejiang Cancer Hospital
2025
Florida College
2015-2022
First Affiliated Hospital of Xiamen University
2022
University of Florida
2015-2022
Shanghai Jiao Tong University
2009-2021
Hershey (United States)
2021
Renji Hospital
2019-2021
HOTTIP lncRNA is highly expressed in acute myeloid leukemia (AML) driven by MLL rearrangements or NPM1 mutations to mediate HOXA topologically associated domain (TAD) formation and drive aberrant transcription. However, the mechanism through which accesses CCCTC-binding factor (CTCF) chromatin boundaries regulates CTCF-mediated genome topology remains unknown. Here, we show that directly interacts with a fraction of CTCF-binding sites (CBSs) AML recruiting CTCF/cohesin complex...
The histone demethylase LSD1 facilitates epithelial-to-mesenchymal transition (EMT) and tumor progression by repressing epithelial marker expression. However, little is known about how its function may be modulated. Here, we report that acetylated in but not mesenchymal cells. Acetylation of reduces association with nucleosomes, thus increasing H3K4 methylation at target genes activating transcription. MOF acetyltransferase interacts responsible for acetylation. preferentially expressed...
Carcinoma cells can acquire increased motility and invasiveness through epithelial-to-mesenchymal transition (EMT). However, the significance of EMT in cancer metastasis has been controversial, exact fates functions vivo remain inadequately understood. Here, we tracked epithelial that underwent inducible or spontaneous various tumor transplantation models. Unlike cells, majority were specifically located perivascular space closely associated with blood vessels. markedly activated multiple...
The Hippo pathway effector TAZ promotes cellular growth, survival, and stemness through regulating gene transcription. Recent studies suggest that liquid-liquid phase separation (LLPS) compartmentalizes key cofactors to activate However, how LLPS is achieved remains unknown. Here, it shown the paraspeckle protein NONO required for activation in nucleus. a TAZ-binding protein. Their interaction shows temporal regulation parallel between TEAD as well expression of target genes. depletion...
Abstract Nucleophosmin ( NPM1 ) is the most commonly mutated gene in acute myeloid leukemia (AML) resulting aberrant cytoplasmic translocation of encoded nucleolar protein (NPM1c + ). NPM1c maintains a unique leukemic expression program, characterized by activation HOXA / B clusters and MEIS1 oncogene to facilitate leukemogenesis. However, mechanisms which controls such patterns promote leukemogenesis remain largely unknown. Here, we show that HOXBLINC , HOXB locus-associated long non-coding...
Although nucleoporin 98 (NUP98) fusion oncogenes often drive aggressive pediatric leukemia by altering chromatin structure and expression of HOX genes, underlying mechanisms remain elusive. Here, we report that a Hoxb-associated lncRNA HoxBlinc was aberrantly activated in NUP98-PHF23 fusion-driven leukemias. occupancies led to elevated MLL1 recruitment aberrant homeotic topologically associated domains (TADs) enhanced accessibilities homeotic/hematopoietic oncogenes. HoxBlinc-depletion NUP98...
Fate determination of germline stem cells remains poorly understood at the chromatin structure level.Our research hopes to develop successful offspring production ovarian organoids derived from spermatogonial (SSCs) by defined factors.The oocytes transdifferentiated mouse SSCs with tracking transplanted in vivo, single cell whole exome sequencing, and 3D culture reconstitution process oogenesis SSCs. The factors were screened organoids. We uncovered extensive reorganization during SSC...
LATS kinase–activating signals selectively modulate CTCF genomic occupancy and 3D genome organization.
Chemoresistance remains the major challenge for successful treatment of acute myeloid leukemia (AML). Although recent mouse studies suggest that response genetically and immunophenotypically indistinguishable AML can be influenced by their different cells origin, corresponding evidence in human disease is still largely lacking. By combining prospective modeling using highly purified hematopoietic stem or progenitor with retrospective deconvolution study (LSCs) from primary patient samples,...
Abstract Aberrant activation of the TAL1 is associated with up to 60% T-ALL cases and involved in CTCF-mediated genome organization within locus, suggesting that CTCF boundary plays a pathogenic role T-ALL. Here, we show −31-Kb binding site (−31CBS) serves as chromatin defines topologically associating domain (TAD) enhancer/promoter interaction required for activation. Deleted or inverted −31CBS impairs expression context-dependent manner. Deletion reduces accessibility blocks long-range...
Receptor-interacting protein kinase 3 (Ripk3) is one of the critical mediators inflammatory cytokine-stimulated signaling. Here we show that Ripk3 signaling selectively regulates both number and function hematopoietic stem cells (HSCs) during stress conditions. not required for normal homeostatic hematopoiesis. However, in response to serial transplantation, inactivation prevents stress-induced HSC exhaustion functional attenuation, while fractionated low doses ionizing radiation (IR),...
Abstract The activity of hematopoietic factor GATA-1 is modulated through p300/CBP-mediated acetylation and FOG-1 mediated indirect interaction with HDAC1/2 containing NuRD complex. Although implicated in activation, the role deacetylation not studied. Here, we found that FOG-1/NuRD does deacetylate GATA-1. However, can directly bind Two arginine residues within linker region mediates direct HDAC1. to alanine mutation (2RA) blocks fails induce erythroid differentiation. Gene expression...
Leukemia, a malignant hematological disease, has poor therapeutic outcomes due to chemotherapeutic resistance. Increasing evidence confirmed that the elevated capacity for DNA damage repair in cancer cells is major mechanism of acquired Thus, combining chemotherapy with inhibitors pathways potentially an ideal strategy treating leukemia. Checkpoint kinase 1 (CHK1) important component response (DDR) and involved G2/M checkpoint. In present study, we demonstrated shRNA‑mediated CHK1 silencing...
The successful isolation and culture of female germline stem cells \(FGSCs) that exist in postnatal adult mammals will allow us to study their biological characteristics applications biotechnology medicine.In this study, we describe systematic procedures for the transplantation FGSCs.To establish mouse FGSC lines, FGSCs were isolated from ovaries mice by enzymatic digestion immunomagnetic puri cation.After culture, transplanted into recipient females sterilized chemotherapy analyze...
Long non-coding RNAs (lncRNAs) play an important role in regulation of HOX genes which aberrant expression becomes a dominant mechanism for leukemic transformation. It remains elusive how HOX-associated lncRNAs regulate HSC function and contribute to leukemogenesis. We found that HOTTIP lncRNA is aberrantly activated many AML patients by regulating the gene-associated chromatin neighborhood gene expression. Knock-out attenuates progressions transplanted mice altering HOXA-associatedleukemic...
Epithelial-mesenchymal transition (EMT) is implicated in tumor metastasis and therapeutic resistance. It remains a challenge to target cancer cells that have undergone EMT. The Snail family of key EMT-inducing transcription factors directly binds transcriptionally represses not only epithelial genes but also myriad additional genomic targets may carry out significant biological functions. Therefore, we reasoned EMT inherently causes various concomitant phenotypes, some which create...