A5024892590- Acute Myeloid Leukemia Research
- Acute Lymphoblastic Leukemia research
- interferon and immune responses
- Protein Degradation and Inhibitors
- RNA Research and Splicing
- RNA modifications and cancer
- Immunotherapy and Immune Responses
- Chronic Lymphocytic Leukemia Research
- Cancer Genomics and Diagnostics
- MicroRNA in disease regulation
- CAR-T cell therapy research
- Cytokine Signaling Pathways and Interactions
- RNA Interference and Gene Delivery
- Chromatin Remodeling and Cancer
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Cutaneous lymphoproliferative disorders research
- Sarcoma Diagnosis and Treatment
- Multiple Myeloma Research and Treatments
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Childhood Cancer Survivors' Quality of Life
- Retinoids in leukemia and cellular processes
- Cancer Mechanisms and Therapy
- Cancer therapeutics and mechanisms
- Immune Response and Inflammation
National University of Singapore
2015-2024
National University Cancer Institute, Singapore
2015-2024
Johns Hopkins Medicine
2023
Johns Hopkins University
2023
Oklahoma State University
2023
University Hospital Ulm
2016
Universität Ulm
2009-2010
Somatic mutations in the spliceosome gene ZRSR2-located on X chromosome-are associated with myelodysplastic syndrome (MDS). ZRSR2 is involved recognition of 3'-splice site during early stages assembly; however, its precise role RNA splicing has remained unclear. Here we characterize as an essential component minor (U12 dependent) assembly. shRNA-mediated knockdown leads to impaired U12-type introns and RNA-sequencing MDS bone marrow reveals that loss activity causes increased mis-splicing....
Acute promyelocytic leukemia (APL) is a subtype of myeloid characterized by differentiation block at the promyelocyte stage. Besides presence chromosomal rearrangement t(15;17), leading to formation PML-RARA (promyelocytic leukemia-retinoic acid receptor alpha) fusion, other genetic alterations have also been implicated in APL. Here, we performed comprehensive mutational analysis primary and relapse APL identify somatic alterations, which cooperate with pathogenesis We explored landscape...
Thymus function is thought to depend on a steady supply of T cell progenitors from the bone marrow. The notion that thymus lacks with self-renewal capacity based transplantation experiments in which host-derived thymocytes replaced thymus-resident cells within 4 wk. grafting into cell–deficient mice resulted wave export thymus, followed by colonization progenitors, and cessation development. Compound Rag2−/−γc−/−KitW/Wv mutants lack competitive hematopoietic stem (HSCs) are devoid...
Abstract Current standard of care for patients with pediatric acute lymphoblastic leukemia (ALL) is mainly effective, high remission rates after treatment. However, the genetic perturbations that give rise to this disease remain largely undefined, limiting ability address resistant tumors or develop less toxic targeted therapies. Here, we report use next-generation sequencing interrogate and pathogenic mechanisms 240 ALL cases their matched samples. Commonly mutated genes fell into several...
ZBTB transcription factors orchestrate gene during tissue development. However, their roles in glioblastoma (GBM) remain unexplored. Here, through a functional screening of genes, we identify that BCL6 is required for GBM cell viability and overexpression associated with worse prognosis. In somatic transgenic mouse model, depletion Bcl6 inhibits the progression KrasG12V-driven high-grade glioma. Transcriptome analysis demonstrates involvement tumor protein p53 (TP53), erythroblastic leukemia...
Partial tandem duplication of MLL (MLL-PTD) characterizes acute myeloid leukemia (AML) patients often with a poor prognosis. To understand the order occurrence MLL-PTD in relation to other major AML mutations and identify novel that may be present this unique molecular subtype, exome targeted sequencing was performed on 85 samples using HiSeq-2000. Genes involved cohesin complex (STAG2), splicing factor (U2AF1) poorly studied gene, MGA were recurrently mutated, whereas NPM1, one most...
Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy having no effective treatment. Laminin subunit-γ-2 (LAMC2) epithelial basement membrane protein involved in cell migration and tumor invasion might represent ideal target for the development of novel therapeutic approaches ATC.The objective investigation was to study role LAMC2 ATC tumorigenesis.LAMC2 expression evaluated by RT-PCR, Western blotting, immunohistochemistry specimens, adjacent noncancerous tissues, lines. The short...
Precise regulation of chromatin architecture is vital to physiological processes including hematopoiesis. ARID1A a core component the mammalian SWI/SNF complex, which one ATP-dependent remodeling complexes. To uncover role in hematopoietic development, we utilized cell-specific deletion Arid1a mice. We demonstrate that essential for maintaining frequency and function stem cells its loss impairs differentiation both myeloid lymphoid lineages. deficiency led global reduction open ensuing...
Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive leukemia of cells (pDC). BPDCN occurs at least three times more frequently in men than women, but the reasons for this sex bias are unknown. Here, studying genomics primary and modeling disease-associated mutations, we link acquired alterations RNA splicing to abnormal pDC development inflammatory response through Toll-like receptors. Loss-of-function mutations ZRSR2, X chromosome gene encoding a factor, enriched...
The anti-apoptotic protein Bcl-2 is a well-known and attractive therapeutic target for cancer. In the present study solution-phase T3P-DMSO mediated efficient synthesis of 2-amino-chromene-3-carbonitriles from alcohols, malanonitrile phenols reported. These novel showed cytotoxicity in human acute myeloid leukemia (AML) cell lines. Compound 4g was found to be most bioactive, decreasing growth increasing apoptosis AML cells. Moreover, compound (at concentration 5 µM) increased G2/M sub-G1...
Abstract Despite the remarkable clinical responses achieved with immune checkpoint blockade therapy, response rate is relatively low and only a subset of patients can benefit from treatment. Aberrant RNA accumulation mediate IFN signaling stimulate an response, suggesting that targeting decay machinery might sensitize tumor cells to immunotherapy. With this in mind, we identified exoribonuclease, XRN1, as potential therapeutic target suppress antitumor immunity. Silencing XRN1 suppressed...
Dppa4 (developmental pluripotency-associated 4) has been identified in several high-profile screens as a gene that is expressed exclusively pluripotent cells. It encodes nuclear protein with an SAP-like domain and appears to be associated preferentially transcriptionally active chromatin. Its exquisite expression pattern results of RNA interference experiments have led speculation Dppa4, well its nearby homolog Dppa2, might play essential roles embryonic stem (ES) cell function and/or germ...
Abstract Alternative lengthening of telomeres (ALT) supports telomere maintenance in 10–15% cancers, thus representing a compelling target for therapy. By performing anti-cancer compound library screen on isogenic cell lines and using extrachromosomal telomeric C-circles, as bona fide marker ALT activity, we identify receptor tyrosine kinase inhibitor ponatinib that deregulates mechanisms, induces dysfunction, reduced ALT-associated synthesis, targets, vivo, ALT-positive cells. Using...