A5033610151- Multiple Myeloma Research and Treatments
- Chemokine receptors and signaling
- Chronic Lymphocytic Leukemia Research
- Cancer, Hypoxia, and Metabolism
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Protein Degradation and Inhibitors
- CAR-T cell therapy research
- Ubiquitin and proteasome pathways
- Monoclonal and Polyclonal Antibodies Research
- Peptidase Inhibition and Analysis
- Glycosylation and Glycoproteins Research
- Boron Compounds in Chemistry
- Phagocytosis and Immune Regulation
- Calcium signaling and nucleotide metabolism
- Cancer-related molecular mechanisms research
- Angiogenesis and VEGF in Cancer
- Cell Adhesion Molecules Research
- Radiopharmaceutical Chemistry and Applications
- Nanoplatforms for cancer theranostics
- Nanoparticle-Based Drug Delivery
- Immune cells in cancer
- Cancer Mechanisms and Therapy
- Hematopoietic Stem Cell Transplantation
- Cancer-related Molecular Pathways
Washington University in St. Louis
2015-2024
Imperial College London
2012
Institute of Rheumatology
2008
Multiple myeloma (MM) remains to be incurable despite recent therapeutic advances. CD47, an immune checkpoint known as the “don’t eat me” signal, is highly expressed on surface of various cancers, allowing cancer cells send inhibitory signals macrophages and impede phagocytosis response. In this study, we hypothesized that blocking signaling using anti-CD47 monoclonal antibody will induce killing MM cells. We report CD47 expression was directly correlated with stage disease, from normal MGUS...
Abstract Drug resistance and dose-limiting toxicities are significant barriers for treatment of multiple myeloma (MM). Bone marrow microenvironment (BMME) plays a major role in drug MM. delivery with targeted nanoparticles have been shown to improve specificity efficacy reduce toxicity. We aim treatments MM by (1) using nanoparticle enhance toxicity; (2) targeting the tumor-associated endothelium specific cargo tumor area, (3) synchronizing chemotherapy (bortezomib; BTZ) BMME-disrupting...
T-cell-based immunotherapy, such as CAR-T cells and bispecific T-cell engagers (BiTEs), has shown promising clinical outcomes in many cancers; however, these therapies have significant limitations, poor pharmacokinetics the ability to target only one antigen on cancer cells. In multiclonal diseases, confer development of antigen-less clones, causing tumor escape relapse. this study, we developed nanoparticle-based (nanoBiTEs), which are liposomes decorated with anti-CD3 monoclonal antibodies...
Bromodomain-containing protein 9 (BRD9), an essential component of the SWI/SNF chromatin remodeling complex termed ncBAF, has been established as a therapeutic target in subset sarcomas and leukemias. Here, we used novel small molecule inhibitors degraders along with RNA interference to assess dependency on BRD9 context diverse hematological malignancies, including acute myeloid leukemia (AML), lymphoblastic (ALL), multiple myeloma (MM) model systems. Following depletion protein, AML cells...
Multiple myeloma (MM) is the cancer of plasma cells within bone marrow and remains incurable. Tumor-associated macrophages (TAMs) tumor microenvironment often display a pro-tumor phenotype correlate with proliferation, survival, therapy resistance. IL-10 key immunosuppressive cytokine that leads to recruitment development TAMs. In this study, we investigated role in MM TAM as well therapeutic application IL-10/IL-10R/STAT3 signaling inhibition. We demonstrated overexpressed BM mediates...
Hypoxia and T-helper cell 1 (Th1) cytokine-driven inflammation are key features of rheumatoid arthritis (RA) contribute to disease pathogenesis by promoting angiogenesis. The objective our study was characterise the angiogenic gene signature RA fibroblast-like synoviocytes (FLS) in response hypoxia, as well Th1 2 (Th2) cytokines, particular dissect out effects combined hypoxia cytokines on inducible transcription factors (HIFs) Human angiogenesis PCR arrays were used screen cDNA from FLS...
The phosphatidylinositide 3-kinase (PI3K) pathway is activated and correlated with drug resistance in multiple myeloma (MM). In the present study we investigated role of PI3KCA (PI3K-α) progression MM. We showed that gene expression isoform was higher MM compared to normal subjects. BYL719, a novel specific inhibitor inhibited survival primary cells cell lines but not peripheral blood mononuclear cells. BYL719 induced apoptosis their cycle by causing G1 arrest. PI3K signalling, decreased...
Abstract Objective Rheumatoid arthritis (RA) is characterized by hypoxia and the expression of hypoxia‐inducible transcription factors (HIFs), which coordinate cellular responses to hypoxia. The objective this study was analyze regulation prolyl hydroxylase domain (PHD) enzymes factor‐inhibiting HIF‐1α (FIH‐1), regulate HIF levels, roles these in RA fibroblast‐like synoviocytes (RA FLS). Methods PHD FIH downstream target genes assessed quantitative polymerase chain reaction Western blotting....
Multiple myeloma (MM) presents a poor prognosis and high lethality of patients due to development drug resistance. P-glycoprotein (P-gp), drug-efflux transporter, is upregulated in MM post-chemotherapy involved the resistance since many anti-myeloma drugs (including proteasome inhibitors) are P-gp substrates. Hypoxia develops bone marrow niche during progression has long been linked chemoresistance. Additionally, hypoxia-inducible transcription factor (HIF-1α) was demonstrated directly...
Waldenström macroglobulinemia, a rare and indolent type of non-Hodgkin lymphoma, is characterized by widespread lymphoplasmacytic B cells in the bone marrow. Previous studies have shown that hypoxic conditions play key role dissemination other hematologic malignancies. In this study, effect hypoxia was tested on progression spread macroglobulinemia. Interestingly, tumor correlated with levels macroglobulinemia marrow number circulating vivo. Mechanistic demonstrated decreased cell cycle, did...
Multiple myeloma (MM) is a plasma cell malignancy localized in the bone marrow. Despite introduction of novel therapies majority MM patients relapse. We have previously shown that inhibition P-selectin and glycoprotein ligand-1 (PSGL-1) play key role proliferation using small-molecule inhibitors P-selectin/PSGL-1 sensitized cells to therapy. However, these had low specificity showed poor pharmacokinetics. Therefore, we tested blocking PSGL-1 functional monoclonal antibodies order sensitize...