A5011679479- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- Cancer Genomics and Diagnostics
- Chemokine receptors and signaling
- Glycosylation and Glycoproteins Research
- T-cell and B-cell Immunology
- HIV/AIDS drug development and treatment
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Cancer Treatment and Pharmacology
- Peptidase Inhibition and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Cancer therapeutics and mechanisms
- Acute Myeloid Leukemia Research
- Epigenetics and DNA Methylation
- Immune Cell Function and Interaction
- Hematological disorders and diagnostics
- Cancer Immunotherapy and Biomarkers
- Single-cell and spatial transcriptomics
- Ubiquitin and proteasome pathways
- Pharmacological Effects and Toxicity Studies
- Cancer Mechanisms and Therapy
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- CRISPR and Genetic Engineering
- Synthesis and Biological Evaluation
Harvard University
2021-2025
Broad Institute
2021-2025
Dana-Farber Cancer Institute
2021-2025
Nantes Université
2019-2023
Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes Angers
2022-2023
Inserm
2019-2023
Centre National de la Recherche Scientifique
2019-2023
Heidelberg University
2023
German Cancer Research Center
2023
Massachusetts Institute of Technology
2023
Abstract Multiple myeloma is a plasma cell malignancy almost always preceded by precursor conditions, but low tumor burden of these early stages has hindered the study their molecular programs through bulk sequencing technologies. Here, we generate and analyze single RNA-sequencing cells from 26 patients at varying disease 9 healthy donors. In silico dissection comparison normal transformed same bone marrow biopsy enables discovery patient-specific transcriptional changes. Using Non-Negative...
Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition multiple myeloma with few known risk factors. The emergence mass spectrometry (MS) for the detection MGUS has provided new opportunities to evaluate its In total, 2628 individuals at elevated were enrolled in screening study and completed an exposure survey (PROMISE trial). Participant samples screened by MS, monoclonal proteins (M-proteins) concentrations ≥0.2 g/L categorized as MS-MGUS. Multivariable...
The translocation t(11;14) occurs in 20% of patients with multiple myeloma (MM) and results the upregulation CCND1. Nearly two-thirds MM cells are BCL2 primed highly responsive to oral inhibitor venetoclax. Although it is evident that this unique sensitivity venetoclax depends on Bcl-2 homology domain 3- proapoptotic protein priming BCL2, biology underlying dependency poorly defined. Importantly, epigenetic regulation transcriptomes its impact gene clinical response remain elusive. In study,...
Structural variants (SVs) can drive tumorigenesis, yet discovering SV cancer drivers remains challenging. Here, we present SVelfie (Structural Variants enriched with likely functional/impactful events), a statistical method to infer driver genes from SVs detected across cohort of genomes, based on enrichment functional events. When testing lymphoma samples the Pan-Cancer Analysis Whole Genomes (PCAWG), it corroborates known tumor suppressor and also yields novel candidates.
Abstract BACKGROUND: Large-scale genomic studies such as The Cancer Genome Atlas (TCGA) and Pan-Cancer Analysis of Whole Genomes (PCAWG) show that the breast cancer (BrCa) genome is dominated by structural variation (SV) rather than single base pair mutations, producing a fertile environment for gene fusions. In this study, we implement rigorous, expression-based approach to create comprehensive landscape fusion RNAs in metastatic (MBC). We find RNAs—many which are novel involving known...
Multiple myeloma (MM) develops from well-defined precursor stages; however, invasive bone marrow (BM) biopsy limits screening and monitoring strategies for patients. We enumerated circulating tumor cells (CTC) 261 patients (84 monoclonal gammopathy of undetermined significance, 155 smoldering multiple myeloma, 22 MM), with neoplastic detected in 84%. developed a novel approach, MinimuMM-seq, which enables the detection translocations copy-number abnormalities through whole-genome sequencing...
Background Genome editing offers unique perspectives for optimizing the functional properties of T cells adoptive cell transfer purposes. So far, PDCD1 has been successfully tested mainly in chimeric antigen receptor (CAR-T) and human primary cells. Nonetheless, patients with solid tumors, effector memory specific tumor antigens remains a relevant option, use high avidity deficient programmed death-1 (PD-1) expression is susceptible to improve therapeutic benefit these treatments. Methods...
The International Myeloma Working Group recently fully incorporated <sup>18</sup>F-FDG PET into multiple myeloma (MM) diagnosis and response evaluation. Moreover, a few studies demonstrated the prognostic value of several biomarkers extracted from this imaging at baseline. Before these could be endorsed as risk classifiers by hematologist community, further characterization underlying molecular aspects was necessary. <b>Methods:</b> Reported (<sup>18</sup>F-FDG avidity, SUV<sub>max</sub>,...
Abstract Background Multiple myeloma (MM) is a heterogeneous plasma cell malignancy that remains challenging to cure. Global hypomethylation correlates with an aggressive phenotype of the disease, while hypermethylation observed at particular regions such as B cell-specific enhancers. The recently discovered active epigenetic mark 5-hydroxymethylCytosine (5hmC) may also play role in tumor biology; however, little known about its level and distribution myeloma. In this study, we investigated...
Among glucocorticoids (GCs), dexamethasone (Dex) is widely used in treatment of multiple myelomas. However, despite a definite benefit, all patients relapse. Moreover, the molecular basis glucocorticoid efficacy remains elusive. To determine genomic response to Dex myeloma cells, we generated bulk and single-cell multi-omics data high-resolution contact maps active enhancers target genes. We show that minority receptor-binding sites are associated with enhancer activity gains, increased...
SUMMARY The development of targeted therapy for patients with Multiple Myeloma (MM) is hampered by the low frequency actionable genetic abnormalities. Gain or amplification chr1q (Amp1q) most frequent arm-level copy number gain in MM, and it associated higher risk progression death despite recent advances therapeutics. Thus, developing MM Amp1q stands to benefit a large portion need more effective management. Here, we employed large-scale dependency screens drug systematically characterize...
Abstract Multiple myeloma is a plasma cell malignancy almost always preceded by precursor conditions, but low tumor burden of these early stages has hindered the study their molecular programs through bulk sequencing technologies. Here, we generated and analyzed single RNA-sequencing cells from 26 patients at varying disease 9 healthy donors. In silico dissection comparison normal transformed same bone marrow biopsy enabled discovery novel, patient-specific transcriptional changes. Using...
MYC deregulation occurs in the majority of multiple myeloma (MM) cases and is associated with progression worse prognosis. Enhanced expression about 70% MM patients, but it known to be driven by translocation or amplification events only ~40% myelomas. Here, we used CRISPR interference (CRISPRi) uncover an epigenetic mechanism regulation whereby increased accessibility a plasma cell-type specific enhancer leads expression. This native activity was not hijacking led binding c-MAF, IRF4, SPIB...