A5076644963- Acute Myeloid Leukemia Research
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- CAR-T cell therapy research
- Epigenetics and DNA Methylation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Retinoids in leukemia and cellular processes
- Ubiquitin and proteasome pathways
- CRISPR and Genetic Engineering
- Nuclear Structure and Function
- Cancer Genomics and Diagnostics
- Cancer therapeutics and mechanisms
- Acute Lymphoblastic Leukemia research
- Immune Cell Function and Interaction
- Chronic Myeloid Leukemia Treatments
- Cancer-related gene regulation
- Advanced biosensing and bioanalysis techniques
- Renal and related cancers
- T-cell and B-cell Immunology
- Diverse academic and cultural studies
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Elder Abuse and Neglect
- Virus-based gene therapy research
- Pluripotent Stem Cells Research
Imperial College London
2025
Campus Bio Medico University Hospital
2025
Azienda Ospedaliero Universitaria Ospedali Riuniti
2023-2024
University of Perugia
2010-2024
Marche Polytechnic University
2022-2023
Baylor College of Medicine
2016-2023
Assistance Publique – Hôpitaux de Paris
2021
Ospedale Santa Maria
2019-2021
Azienda Ospedaliera di Perugia
2020-2021
Hôpital Européen Georges-Pompidou
2021
Highlights•Gene knockout of primary murine HSPCs with efficiencies routinely higher than 60%•Gene human and T cells from 75% to 90%•CRISPR/Cas9 homology-directed repair in >20% HSPCsSummaryOur understanding the mechanisms that regulate hematopoietic stem/progenitor (HSPCs) has been advanced by ability genetically manipulate mice; however, germline modification is time consuming expensive. Here, we describe fast, efficient, cost-effective methods directly modify genomes mouse using...
DNA methylation has widespread effects on gene expression during development. However, our ability to assign specific function regions of is limited by the poor correlation between global patterns and expression.Here, we utilize nuclease-deactivated Cas9 protein fused repetitive peptide epitopes (SunTag) recruiting multiple copies antibody-fused de novo methyltransferase 3A (DNMT3A) (dCas9-SunTag-DNMT3A) amplify local DNMT3A concentration methylate genomic sites interest. We demonstrate that...
Abstract Chimeric antigen receptor (CAR) T-cells targeting CD19 demonstrate remarkable efficacy in treating B-lineage acute lymphoblastic leukemia (BL-ALL), yet up to 39% of treated patients relapse with CD19(−) disease. We report that escape is associated downregulation, but preservation, targetable expression CD20 and CD22. Accordingly, we reasoned broadening the spectrum CD19CAR include both CD22 would enable them target BL-ALL while preserving their upfront efficacy. created a...
Clonal hematopoiesis is a prevalent age-related condition associated with greatly increased risk of hematologic disease; mutations in DNA methyltransferase 3A (DNMT3A) are the most common driver this state. DNMT3A variants occur across gene some particularly malignancy, but functional relevance and mechanisms pathogenesis majority unknown. Here, we systematically investigated activity protein stability 253 disease-associated mutations, found that 74% were loss-of-function mutations. Half...
Abstract Acute myeloid leukemia (AML) pathogenesis often involves a mutation in the NPM1 nucleolar chaperone, but bases for its transforming properties and overall association with favorable therapeutic responses remain incompletely understood. Here we demonstrate that an oncogenic mutant form of (NPM1c) impairs mitochondrial function. NPM1c also hampers formation promyelocytic (PML) nuclear bodies (NB), which are regulators fitness key senescence effectors. Actinomycin D (ActD), antibiotic...
NPM 1-mutated acute myeloid leukemia (AML) shows unique features. However, the characteristics of "therapy-related" NPM1-mutated AML (t-NPM1 AML) are poorly understood. We compared genetics, transcriptional profile, and clinical outcomes t-NPM1 AML, de novo (dn-NPM1 AML), therapy-related (t-AML) with wild-type NPM1 (t-AML). Normal karyotype was more frequent in (n = 78/96, 88%) dn-NPM1 1986/2394, than t-AML 103/390, 28%; P < .001). DNMT3A TET2 were mutated 43% 40% 107), similar to 88, 48%...
Abstract It is well established that pluripotent stem cells in fetal and postnatal liver (LPCs) can differentiate into both hepatocytes cholangiocytes. However, the signaling pathways implicated differentiation of LPCs are still incompletely understood. Transcription Factor EB (TFEB), a master regulator lysosomal biogenesis autophagy, known to be involved osteoblast myeloid differentiation, but its role lineage commitment has not been investigated. Here we show during development upon...
NPM1 is the most frequently mutated gene in adults with acute myeloid leukemia (AML). The interaction between mutant (NPM1c) and exportin-1 (XPO1) causes aberrant cytoplasmic dislocation of NPM1c promotes high expression homeobox (HOX) genes, which critical for maintaining leukemic state NPM1-mutated cells. Although there a rationale using XPO1 inhibitors AML, selinexor administered once or twice per week did not translate into clinical benefit patients mutations. Here, we show that this...
Capicua (CIC) regulates a transcriptional network downstream of the RAS/MAPK signaling cascade. In Drosophila , CIC is important for many developmental processes, including embryonic patterning and specification wing veins. humans, has been implicated in neurological diseases, spinocerebellar ataxia type 1 (SCA1) neurodevelopmental syndrome. Additionally, we others have reported mutations several cancers. However, whether tumor suppressor remains to be formally tested. this study, found that...