A5101836049- Hemophilia Treatment and Research
- Platelet Disorders and Treatments
- Retinoids in leukemia and cellular processes
- Chronic Myeloid Leukemia Treatments
- Cell Adhesion Molecules Research
- Virus-based gene therapy research
- Chronic Lymphocytic Leukemia Research
- Blood properties and coagulation
- Acute Myeloid Leukemia Research
- Blood Coagulation and Thrombosis Mechanisms
- Protein Degradation and Inhibitors
- CAR-T cell therapy research
- Click Chemistry and Applications
- Cellular Mechanics and Interactions
- Antioxidant Activity and Oxidative Stress
- Heparin-Induced Thrombocytopenia and Thrombosis
- Acute Lymphoblastic Leukemia research
- Eosinophilic Disorders and Syndromes
- Antiplatelet Therapy and Cardiovascular Diseases
- Immunodeficiency and Autoimmune Disorders
- Venous Thromboembolism Diagnosis and Management
- Cancer therapeutics and mechanisms
- Cancer-related gene regulation
- Lipid metabolism and disorders
- Wnt/β-catenin signaling in development and cancer
Ruijin Hospital
2016-2025
Shanghai Jiao Tong University
2016-2025
Shanghai Institute of Hematology
2016-2025
Center for Life Sciences
2016
Institute of Zoology
2009
Chinese Academy of Sciences
2009
In this study, we show that combined use of Imatinib (IM) and arsenic sulfide [As 4 S (AS)] exerts more profound therapeutic effects in a BCR / ABL -positive mouse model chronic myeloid leukemia (CML) than either drug as single agent. A systematic analysis dynamic changes the proteome, phosphoproteome, transcriptome K562 cells after AS and/or IM treatment was performed to address mechanisms underlying synergy. Our data indicate promotes activities unfolded protein reaction (UPR)...
Arsenic, a curative agent for acute promyelocytic leukemia, induces cell apoptosis and degradation of BCR-ABL in chronic myelogenous leukemia (CML). We demonstrated that ubiquitination was mediated by c-CBL, RING-type E3 ligase also shown to be involved many other receptor/protein tyrosine kinases. Our data showed c-CBL protein considerably up-regulated arsenic sulfide (As(4)S(4)). Interestingly, directly bound the RING finger domain inhibit its self-ubiquitination/degradation without...
Abstract Non-small cell lung cancer (NSCLC) is characterized by hyperexpression and/or gain-of-function mutations of the epidermal growth factor receptor (EGFR), resulting in an elevated overall kinase activity. Gefitinib remarkably effective patients with L858R or ΔE746-A750-mutated EGFR. However, drug resistance tends to develop because emergence T790M mutation on New strategies other than repressing activity are thus required treat NSCLC, thereby circumventing resistance. In this study,...
Abstract Aims Dedicator of Cytokinesis 2 (DOCK2), a member the DOCK family Guanine nucleotide exchange factors that specifically act on Rho GTPases including Rac and Cdc42, plays pivotal roles in regulation leukocyte homeostasis. However, its functions platelets remain unknown. Methods Results Using mice with genetic deficiency DOCK2 (Dock2-/-), we showed Dock2-/-mice exhibited macrothrombocytopenic phenotype characterized as decreased platelet count enlarged size by transmission electron...
Metaxin-2 (Mtx2) is an evolutionarily conserved mitochondrial outer membrane protein. Mutations in human Mtx2 cause mandibuloacral dysplasia (MADaM), a progeroid disorder. However, the pathologic mechanisms of loss-of-function remain largely unknown. Using Drosophila, we show null mutants exhibit pupal lethality, rescued by Drosophila or Mtx2, underscoring functional conservation across species. Tissue-specific conditional knockout and rescue experiments reveal muscle as critical site dMtx2...
To clarify whether arsenic could exert inhibitory effects on tumor cells in pleural effusions of patients with non-small cell lung cancer (NSCLC), 36 NSCLC effusion samples were collected from Changzheng Hospital and Ruijin Hospital, 2019 to 2022. The genotype epidermal growth factor receptor (
Conventional antiplatelet agents indiscriminately inhibit both thrombosis and hemostasis, the increased bleeding risk thus hampers their use at more aggressive dosages to achieve adequate effect. Blocking integrin αIIbβ3 outside-in signaling by separating β3/Src interaction, yet be proven in vivo, may nonetheless resolve this dilemma. Identification of a specific druggable target for strategy remains fundamental challenge as Src SH3 is known responsible binding not only β3 but also proteins...
Previous studies in Chinese hamster ovary cells showed that truncational mutations of β3 at sites F754 and Y759 mimicking calpain cleavage regulate integrin signaling. The roles the sequence from to C-terminus conservative N756ITY759 motif platelet function have yet be elaborated. Mice expressing with truncations, or NITY deletion (β3-ΔTNITYRGT, β3-ΔRGT, β3-ΔNITY) were established through transplanting homozygous β3-deficient mouse bone marrow infected by GFP tagged MSCV MigR1 retroviral...
Objective: Integrin β3 is implicated in numerous biological processes such as its relevance to blood triglyceride, yet whether deficiency affects this metabolic process remains unknown. Approach and Results: We showed that the Chinese patients with β3-deficient Glanzmann thrombasthenia had a 2-fold higher serum triglyceride level together lower LPL (lipoprotein lipase) than those an αIIb or healthy subjects. The knockout mice recapitulated these phenotypic features. elevated plasma was due...
Significance Application scope, underlying mechanisms, and potential limitation of AAV/CRISPR-mediated hepatic gene editing remain unexplored. Here we report that a synthetic enhancer/promoter (P2) incorporation empowered AAV/CRISPR to restore FIX-encoding capacity severe F9 defect involving the regulatory region. Systemic analyses revealed critical role host cell heterogenicity in determining therapeutic benefit this regimen, wherein subclinical inflammation posttreatment regulated P2...
Objective: To evaluate the effects of adeno-associated virus (AAV) carrying hFⅧ by serotype 8 (AAV8/hFⅧ) on hemophilia A (HA) mice gene therapy strategy. Methods: pAAV-CB-EGFP, pH22 (serotype 2) and pfΔ6 (adenovirus helper) were used to package AAV into HEK-293 cells in different conditions (ratios plasmids). The efficiency transfection infection evaluated using immunofluorescence microscope seek an optimized condition. pAAV-TTR-hFⅧ, pH 28 8) applied AAV8/hFⅧ purified intravenously injected...
To explore the interaction domains between BCR-ABL and E3 liagase c-CBL, so as to reveal structure-basis for arsenic treat chronic myelogenous leukemia(CML).The interactional interface of c-CBL was simulated analyzed according available structure model. Based on structural information, WT mutant Migr1-BCR-ABL-GFP (ΔSH2,ΔTyrKC,ΔSH2/TyrKC (S/H) pFlag-c-CBL (ΔRF) were constructed co-transfected into 293T HeLa cells. The co-immunoprecipitation (Co-IP) performed by using M2 beads (anti-Flag),...