A5084152812- Acute Myeloid Leukemia Research
- MicroRNA in disease regulation
- Acute Lymphoblastic Leukemia research
- Lung Cancer Treatments and Mutations
- CAR-T cell therapy research
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Lymphoma Diagnosis and Treatment
- RNA Interference and Gene Delivery
- Mesenchymal stem cell research
- Protein Tyrosine Phosphatases
- Cytokine Signaling Pathways and Interactions
- Extracellular vesicles in disease
- Epigenetics and DNA Methylation
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- RNA Research and Splicing
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Chronic Lymphocytic Leukemia Research
- Single-cell and spatial transcriptomics
- Occupational and environmental lung diseases
- Chronic Myeloid Leukemia Treatments
- Cancer Genomics and Diagnostics
- Chromosomal and Genetic Variations
- Hematological disorders and diagnostics
New York University
2016-2025
Candiolo Cancer Institute
2024-2025
NYU Langone Health
2019-2022
NYU Langone’s Laura and Isaac Perlmutter Cancer Center
2021
The San Raffaele Telethon Institute for Gene Therapy
2012-2017
Vita-Salute San Raffaele University
2010-2016
University of Turin
2006-2013
San Raffaele University of Rome
2013
Investigating how chromatin organization determines cell-type-specific gene expression remains challenging. Experimental methods for measuring three-dimensional organization, such as Hi-C, are costly and have technical limitations, restricting their broad application particularly in high-throughput genetic perturbations. We present C.Origami, a multimodal deep neural network that performs de novo prediction of using DNA sequence two genomic features-CTCF binding accessibility. C.Origami...
Lifelong blood cell production is governed through the poorly understood integration of cell-intrinsic and -extrinsic control hematopoietic stem (HSC) quiescence activation. MicroRNAs (miRNAs) coordinately regulate multiple targets within signaling networks, making them attractive candidate HSC regulators. We report that miR-126, a miRNA expressed in early progenitors, plays pivotal role restraining cell-cycle progression vitro vivo. miR-126 knockdown by using lentiviral sponges increased...
Anaplastic large cell lymphomas (ALCLs) represent a subset of in which the anaplastic lymphoma kinase (ALK) gene is frequently fused to nucleophosmin (NPM) gene. We previously demonstrated that constitutive phosphorylation ALK chimeric proteins sufficient induce cellular transformation vitro and vivo activity strictly required for survival ALK-positive ALCL cells. To elucidate signaling pathways ALK-mediated tumor maintenance, we analyzed transcriptomes multiple lines, abrogating their by...
Abstract Anaplastic large cell lymphomas (ALCL) are mainly characterized by the reciprocal translocation t(2;5)(p23;q35) that involves anaplastic lymphoma kinase (ALK) gene and generates fusion protein NPM-ALK with intrinsic tyrosine activity. triggers several signaling cascades, leading to increased growth, resistance apoptosis, changes in morphology migration of transformed cells. To search for new interacting molecules, we developed a mass spectrometry–based proteomic approach HEK293...
Abstract Pulmonary disease increases the risk of developing abdominal aortic aneurysms (AAA). However, mechanism underlying pathological dialogue between lungs and aorta is undefined. Here, we find that inflicting acute lung injury (ALI) to mice doubles their incidence AAA accelerates macrophage-driven proteolytic damage wall. ALI-induced HMGB1 leaks captured by arterial macrophages thereby altering mitochondrial metabolism through RIPK3. RIPK3 promotes fission leading elevated oxidative...
While the mutational landscape across early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) and ETP-like is known, establishing a unified framework that activates stem cell genes characteristic of these tumors remains elusive. Using complementary mouse human models, chromatin mapping, enhancer profiling, we show coactivator ZMIZ1 promotes normal malignant ETP population growth by inducing transcription factor MYB in feedforward circuits to convergently activate oncogenes (MEF2C,...
Abstract Timed degradation of the cyclin-dependent kinase inhibitor p27 Kip1 by E3 ubiquitin ligase F-box protein SKP2 is critical for T-cell progression into cell cycle, coordinating proliferation and differentiation processes. expression regulated mitogenic stimuli Notch signaling, a key pathway in development acute lymphoblastic leukemia (T-ALL); however, it not known whether plays role T-ALL. Here, we determined that function relevant T-ALL leukemogenesis, whereas dispensable...
In non-small cell lung cancer (NSCLC), receptor tyrosine kinases (RTKs) stand out among causal dominant oncogenes, and the ablation of RTK signaling has emerged as a novel tailored therapeutic strategy. Nonetheless, long-term inhibition leads invariably to acquired resistance, tumor recurrence metastatic dissemination. ALK+ lines, ALK was associated with coactivation several RTKs, whose pharmacological suppression reverted partial resistance blockade. Remarkably, ERBB2 synergized contributed...
Abstract T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive and often incurable disease. To uncover therapeutic vulnerabilities, we first developed T-ALL patient–derived tumor xenografts (PDXs) exposed PDX cells to a library of 433 clinical-stage compounds in vitro. We identified 39 broadly active drugs with antileukemia activity. Because endothelial (ECs) can alter drug responses T-ALL, EC/T-ALL coculture system. found that ECs provide protumorigenic signals mitigate PDXs. Whereas...
Abstract The mammalian genome is spatially organized in the nucleus to enable cell type-specific gene expression. Investigating how chromatin organization determines this specificity remains a challenge. Methods for measuring 3D organization, such as Hi-C, are costly and bear strong technical limitations, restricting their broad application particularly high-throughput genetic perturbations. In study, we present C.Origami, deep neural network model that performs de novo prediction of...
ABSTRACT Three-dimensional (3D) chromatin architectural changes can alter the integrity of topologically associated domains (TADs) and rewire specific enhancer-promoter interactions impacting gene expression. Recently, such alterations have been implicated in human disease, highlighting need for a deeper understanding their role. Here, we investigate reorganization architecture T cell acute lymphoblastic leukemia (T-ALL) using primary specimens its dynamic responses to pharmacological...
223Ra is a bone-seeking, α-particle-emitting radionuclide approved for the treatment of patients with metastatic prostate cancer and currently being tested in variety clinical trials primary cancers to bone. Clinical evaluation hematologic safety showed significantly increased rate neutropenia thrombocytopenia patients, hinting at myelosuppression as side effect. Methods: In this study, we investigated consequences on bone marrow biology by combining flow cytometry, single-cell RNA...
Blood homeostasis requires the daily production of millions terminally differentiated effector cells that all originate from hematopoietic stem (HSCs). HSCs are rare and exhibit unique self-renewal multipotent properties, which depend on their ability to maintain quiescence through ill-defined processes. Defective control cell cycle progression can eventually lead bone marrow failure or malignancy. In particular, molecular mechanisms tying re-entry fate commitment in remain elusive. Previous...
Abstract/Summary To maintain blood homeostasis, millions of terminally differentiated effector cells are produced every day. At the apex this massive and constant production lie hematopoietic stem (HSCs), a rare cell type harboring unique self-renewal multipotent properties. A key feature HSCs is their ability to temporarily exit cycle in state termed quiescence. Defective control progression can eventually lead bone marrow failure or malignant transformation. It thought that must re-enter...