A5081719550- Acute Myeloid Leukemia Research
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Hematopoietic Stem Cell Transplantation
- Retinoids in leukemia and cellular processes
- Multiple Myeloma Research and Treatments
- Genomics and Chromatin Dynamics
- Immune Cell Function and Interaction
- Neutropenia and Cancer Infections
- Glioma Diagnosis and Treatment
- RNA modifications and cancer
- Amino Acid Enzymes and Metabolism
- Chronic Lymphocytic Leukemia Research
- Enzyme Structure and Function
- Immune cells in cancer
- Ubiquitin and proteasome pathways
- Cancer Genomics and Diagnostics
- Biomedical Research and Pathophysiology
- Circadian rhythm and melatonin
- T-cell and B-cell Immunology
- Acute Lymphoblastic Leukemia research
- Genetics and Neurodevelopmental Disorders
- RNA Research and Splicing
- Lymphoma Diagnosis and Treatment
Beijing Institute of Genomics
2016-2025
Chinese Academy of Sciences
2016-2025
The University of Texas Health Science Center at San Antonio
2021-2025
University of Chinese Academy of Sciences
2019-2025
The University of Texas at San Antonio
2025
Shanghai Center For Bioinformation Technology
2025
Mays Cancer Center at UT Health San Antonio
2023
One Cell Systems (United States)
2023
May Institute
2023
The bone marrow (BM) niche is critical in regulating hematopoiesis, and sexual dimorphism its underlying mechanism BM impact on hematopoiesis are not well understood. We show that male mice exhibited a higher abundance of leptin-receptor-expressing mesenchymal stromal cells (LepR-MSCs) compared to female mice. Sex-mismatched co-culture transplantation showed the provided superior support for vitro colony formation vivo hematopoietic engraftment. co-transplantation significantly enhanced...
Abstract Bromodomain‐containing protein 4 (BRD4) is overexpressed and functionally implicated in various myeloid malignancies. However, the role of BRD4 normal hematopoiesis remains largely unknown. Here, utilizing an inducible Brd4 knockout mouse model, we find that deletion ( Δ/Δ ) hematopoietic system impairs stem cell (HSC) self‐renewal differentiation, which associates with cycle arrest senescence. ATAC‐seq analysis shows increased chromatin accessibility stem/progenitor cells...
Abstract SETD2, a frequently mutated epigenetic tumor suppressor in acute leukemia, is associated with chemotherapy resistance and poor patient outcomes. To explore potential therapeutics for SETD2-mutant we employed an integrated approach combining computational prediction compound library screening. This identified G9a inhibitors as promising candidates, capable of reversing gene expression signatures Setd2 deficiency selectively inhibiting SETD2-deficient cells. RNA-sequencing analysis...
Abstract Intrinsic resistance to anti-HER2 therapy in breast cancer remains an obstacle the clinic, limiting its efficacy. However, biological basis for intrinsic is poorly understood. Here we performed a CRISPR/Cas9-mediated loss-of-function genetic profiling and identified TALDO1 , which encodes rate-limiting transaldolase (TA) enzyme non-oxidative pentose phosphate pathway, as essential cellular survival following pharmacological HER2 blockade. Suppression of TA increases cell...
Acute myeloid leukemia (AML) that evolves from myeloproliferative neoplasm (MPN) is known as post-MPN AML. Current treatments don't significantly extend survival beyond 12 months. BCL-xL has been found to be overexpressed in leucocytes MPN patients, making it a potential therapeutic target. We investigated the role of AML and tested efficacy DT2216, platelet-sparing proteolysis-targeting chimera (PROTAC), preclinical models BCL2L1, gene encoding BCL-xL, expressed at higher levels patients...
Abstract Neurofibromin 1 (NF1) is a tumor suppressor gene frequently mutated in myeloid leukemias. The encoded neurofibromin protein negatively regulates the RAS pathway cytosol. Inactivating mutations NF1 lead to hyperactive signaling, phenocopying activating itself. This aberrant signaling drives downstream activation of pathways such as MAPK and PI3K/Akt/mTOR. Despite prevalence NF1-mutated leukemia, effective therapies remain elusive, highlighting need for deeper understanding...
Standard chemotherapy regimens for remission induction of pediatric acute myeloid leukemia (AML) are associated with significant morbidity and mortality. We performed a cohort study to determine the impact reducing intensity on outcomes selected children AML treated low-dose regimen plus granulocyte colony stimulating factor (G-CSF) (low-dose (LDC)/G-CSF). Complete response (CR) after two courses was attained in 87.0% (40/46) patients receiving LDC/G-CSF. Post-remission therapy offered all...
INTS11, the catalytic subunit of Integrator (INT) complex, is crucial for biogenesis small nuclear RNAs and enhancer RNAs. However, role INTS11 in hematopoietic stem progenitor cell (HSPC) biology unknown. Here, we report that required normal hematopoiesis hematopoietic-specific genetic deletion Ints11 leads to cycle arrest impairment fetal adult HSPCs. We identified a novel INTS11-interacting protein Polycomb repressive complex 2 (PRC2), maintains HSPC functions. Loss destabilizes PRC2...
ASXL1 mutation frequently occurs in all forms of myeloid malignancies and is associated with aggressive disease poor prognosis. recruits Polycomb repressive complex 2 (PRC2) to specific gene loci repress transcription through trimethylation histone H3 on lysine 27 (H3K27me3). alterations reduce H3K27me3 levels, which results leukemogenic expression the development malignancies. Standard therapies for have limited efficacy when mutated present. We discovered upregulation demethylase 6B...
Abstract Rearrangements of the mixed lineage leukemia (MLLr) gene are frequently associated with aggressive acute myeloid (AML). However, treatment options limited due to genomic complexity and dynamics 3D structure, which regulate oncogene transcription development. Here, we carried out an integrative analysis genome chromatin accessibility, expression in gene-edited MLL-AF9 AML samples. Our data revealed profound MLLr-specific alterations A/B compartments, topologically associating domains...