A5083766150- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- Protein Degradation and Inhibitors
- Acute Myeloid Leukemia Research
- Acute Lymphoblastic Leukemia research
- Protein Kinase Regulation and GTPase Signaling
- Ubiquitin and proteasome pathways
- Eosinophilic Disorders and Syndromes
- Retinoids in leukemia and cellular processes
- HER2/EGFR in Cancer Research
- Cytokine Signaling Pathways and Interactions
- Melanoma and MAPK Pathways
- Epigenetics and DNA Methylation
- Viral Infections and Immunology Research
- Histone Deacetylase Inhibitors Research
- Advanced Breast Cancer Therapies
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- CAR-T cell therapy research
- Viral gastroenteritis research and epidemiology
- Immune Cell Function and Interaction
- PI3K/AKT/mTOR signaling in cancer
- Single-cell and spatial transcriptomics
- Fungal Plant Pathogen Control
- Synthesis and biological activity
- Microtubule and mitosis dynamics
Hainan Medical University
2023-2025
Shanghai Jiao Tong University
2015-2025
Ruijin Hospital
2015-2025
Shanghai Institute of Hematology
2015-2025
Beijing Microelectronics Technology Institute
2024
Hainan Medical College Hospital
2024
Brandeis University
2013-2023
Mylan (Switzerland)
2019
Chinese Academy of Sciences
2011
Cancer Research Institute
2003
The Src homology 3 (SH3) region is a small protein domain present in very large group of proteins, including cytoskeletal elements and signaling proteins. It believed that SH3 domains serve as modules mediate protein-protein associations and, along with 2 (SH2) domains, regulate cytoplasmic signaling. binding sites two proteins were localized to nine- or ten-amino acid stretch rich proline residues. Similar motifs exist the formins, function pattern formation embryonic limbs mouse, one...
A human poliovirus receptor (PVR) gene was used to generate transgenic mice that express PVR transcripts and binding sites in a wide range of tissues. Intracerebral inoculation with type 1, Mahoney strain, resulted viral replication the brain spinal cord development paralytic poliomyelitis. P1/Mahoney did not replicate or cause paralysis nontransgenic mice. failed develop clinical disease when inoculated intracerebrally live attenuated Sabin 1 vaccine strain. These results demonstrate is...
Genomic landscapes of 92 adult and 111 pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) were investigated using next-generation sequencing copy number alteration analysis. Recurrent gene mutations fusions tested in an additional 87 93 patients. Among the 29 newly identified in-frame fusions, those involving MEF2D ZNF384 clinically relevant demonstrated to perturb differentiation, EP300-ZNF384 inducing mice. Eight expression subgroups associated characteristic genetic...
To understand the normal and oncogenic functions of protein-tyrosine kinase Abl, yeast two-hybrid system has been used for identifying proteins that interact with it. One interacting protein is Crk-I, an SH3/SH2-containing adapter was originally identified as element in avian sarcoma virus CT10. Direct interaction between Crk-I SH3 Abl at novel, approximately 10 amino acid sites just carboxy-terminal to domain occurs vitro mammalian cells. There a nearby site specific binding another...
The human Kv1.5 potassium channel (hKv1.5) contains proline-rich sequences identical to those that bind Src homology 3 (SH3) domains. Direct association of the tyrosine kinase with cloned hKv1.5 and native in myocardium was observed. This interaction mediated by motif SH3 domain Src. Furthermore, phosphorylated, current suppressed, cells coexpressing v-Src. These results provide direct biochemical evidence for a signaling complex composed protein kinase.
Src homology 2 (SH2) domains provide specificity to intracellular signaling by binding specific phosphotyrosine (phospho-Tyr)-containing sequences. We recently developed a technique using degenerate phosphopeptide library predict the of individual SH2 (src family members, Abl, Nck, Sem5, phospholipase C-gamma, p85 subunit phosphatidylinositol-3-kinase, and SHPTP2 (Z. Songyang, S. E. Shoelson, M. Chaudhuri, G. Gish, T. Pawson, W. Haser, F. King, Roberts, Ratnofsky, R. J. Lechleider, B. Neel,...
Acquisition of additional genetic and/or epigenetic abnormalities other than the BCR / ABL fusion gene is believed to cause disease progression in chronic myeloid leukemia (CML) from phase blast crisis (BC). To gain insights into underlying mechanisms BC, we screened DNA samples CML patients during transformation for mutations a number transcription factor genes that are critical myeloid–lymphoid development. In 85 cases transformation, identified two new coding region GATA-2 , negative...
Imatinib-insensitive leukemia stem cells (LSCs) are believed to be responsible for resistance BCR-ABL tyrosine kinase inhibitors and relapse of chronic myelogenous (CML). Identifying therapeutic targets eradicate CML LSCs may a strategy cure CML. In the present study, we discovered positive feedback loop between protein arginine methyltransferase 5 (PRMT5) in cells. Overexpression PRMT5 was observed human LSCs. Silencing with shRNA or blocking activity small-molecule inhibitor PJ-68 reduced...
The full-length AML1-ETO ( AE ) fusion gene resulting from t(8;21)(q22;q22) in human acute myeloid leukemia (AML) is not sufficient to induce animals, suggesting that additional mutations are required for leukemogenesis. We and others have identified activating of C-KIT nearly half patients with t(8;21) AML. To test the hypothesis cooperate cause overt AML, we generated a murine transduction transplantation model both mutated . overcome intracellular transport block cells, engineered hybrid...
Significance To get more insights into the disease mechanism of T-cell acute lymphoblastic leukemia (T-ALL), particularly in an adult group, we addressed genomic landscape 130 patients, including 61 cases T-ALL. A number new genetic aberrations were identified using integrated transcriptome and analysis. Distinct T-ALL subgroups defined according to interplay among different abnormalities gene transcription patterns. Characterization features is valuable not only for a better understanding...
Abstract Backgrounds Immune checkpoint blockade (ICB) is widely considered to exert long-term treatment benefits by activating antitumor immunity. However, many cancer patients show poor clinical responses ICB due in part the lack of an immunogenic niche. Focal adhesion kinase (FAK) frequently amplified and acts as immune modulator across types. evidence illustrates that targeting FAK most effective combination therapy rather than monotherapy. Methods Here, we used drug screening, vitro vivo...
Clonal hematopoiesis (CH) represents the clonal expansion of hematopoietic stem cells and their progeny driven by somatic mutations. Accurate risk assessment CH is critical for disease prevention clinical decision-making. The size has been showed to associate with higher risk, yet, factors influencing are unknown. In addition, characteristics in long-lived individuals not well documented. Here, we report an in-depth analysis longevous (≥90 y old) common (60~89 elderly groups. Utilizing...
The poliovirus P2/P712 strain is an attenuated virus that closely related to the type 2 Sabin vaccine strain. By using a mouse model for poliomyelitis, sequences responsible attenuation of were previously mapped 5' noncoding region genome and central encoding VP1, 2Apro, 2B, part 2C. To identify specific determinants attenuate strain, recombinants between this mouse-adapted P2/Lansing constructed their neurovirulence in mice was determined. approach, determinant capsid protein VP1. Candidate...
A transgenic mouse model was used to address an unsolved question in the pathogenesis of poliomyelitis: how poliovirus invades central nervous system (CNS). LD50 values for intramuscular and intracerebral inoculation mice expressing receptors (TgPVR mice) were similar. After with poliovirus, paralysis observed first inoculated limb. In contrast, localization initial limb not normal intramuscularly mouse-adapted P2/Lansing strain. inoculation, infectious detected inferior segment spinal cord,...
Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder resulting from the neoplastic transformation of hematopoietic stem cell. The majority cases CML are associated with (9;22) chromosome translocation that generates bcr-abl chimeric gene. Alpha interferon (IFN-alpha) treatment induces hematological remission and prolongs life in 75% patients chronic phase. It has been shown mice deficient consensus sequence binding protein (ICSBP), member regulatory factor family,...
Expression of the human poliovirus receptor (PVR) in transgenic mice results susceptibility to infection. In primate host, infection is characterized by restricted tissue tropism. To determine pattern tropism PVR mice, gene expression and were examined situ hybridization. RNA expressed at high levels neurons central peripheral nervous system, developing T lymphocytes thymus, epithelial cells Bowman's capsule tubules kidney, alveolar lung, endocrine adrenal cortex, it low intestine, spleen,...