A5006068456- Acute Myeloid Leukemia Research
- Blood disorders and treatments
- Multiple Myeloma Research and Treatments
- Telomeres, Telomerase, and Senescence
- Wnt/β-catenin signaling in development and cancer
- Histone Deacetylase Inhibitors Research
- Erythrocyte Function and Pathophysiology
- Single-cell and spatial transcriptomics
- Immunodeficiency and Autoimmune Disorders
- Parvovirus B19 Infection Studies
- Metabolomics and Mass Spectrometry Studies
- Autophagy in Disease and Therapy
- Cancer, Hypoxia, and Metabolism
- interferon and immune responses
- Protein Degradation and Inhibitors
- RNA Interference and Gene Delivery
- Hematopoietic Stem Cell Transplantation
- Cancer therapeutics and mechanisms
- RNA Research and Splicing
- Sirtuins and Resveratrol in Medicine
- Curcumin's Biomedical Applications
- Cancer-related gene regulation
- Adipose Tissue and Metabolism
- Immune cells in cancer
- PARP inhibition in cancer therapy
The University of Texas MD Anderson Cancer Center
2019-2024
University of Trento
2015-2023
Mahidol University
2012-2021
Abstract Myelodysplastic syndromes (MDS) are heterogeneous neoplastic disorders of hematopoietic stem cells (HSCs). The current standard care for patients with MDS is hypomethylating agent (HMA)-based therapy; however, almost 50% fail HMA therapy and progress to acute myeloid leukemia, facing a dismal prognosis due lack approved second-line treatment options. As cancer the seeds disease progression, we investigated biological properties HSCs that drive evolution, seeking uncover...
Abstract Post-transcriptional regulation is an essential determinant of gene expression programs in physiological and pathological conditions. HuR a RNA-binding protein that orchestrates the stabilization translation mRNAs, critical inflammation tumor progression, including necrosis factor-alpha (TNF). We identified low molecular weight compound 15,16-dihydrotanshinone-I (DHTS), well known traditional Chinese medicine practice, through validated high throughput screening on set...
The human antigen R (HuR) is an RNA-binding protein known to modulate the expression of target mRNA coding for proteins involved in inflammation, tumorigenesis, and stress responses a valuable drug target. We previously found that dihydrotanshinone-I (DHTS, 1) prevents association HuR with its RNA substrate, thus imparing function. Herein, inspired by DHTS structure, we designed synthesized array ortho-quinones (tanshinone mimics) using function-oriented synthetic approach. Among others,...
RAS pathway mutations, which are present in 30% of patients with chronic myelomonocytic leukemia (CMML) at diagnosis, confer a high risk resistance to and progression after hypomethylating agent (HMA) therapy, the current standard care for disease. Here, using single-cell, multi-omics technologies, we seek dissect biological mechanisms underlying initiation pathway-mutated CMML. We identify that mutations induce transcriptional reprogramming hematopoietic stem progenitor cells (HSPCs)...
Inhibitors of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in NAD+ biosynthesis from nicotinamide, exhibit anticancer effects preclinical models. However, continuous exposure to NAMPT inhibitors, such as FK866, can induce acquired resistance. We developed FK866-resistant CCRF-CEM (T cell acute lymphoblastic leukemia) and MDA MB231 (breast cancer) models, by exploiting an integrated approach based on genetic, biochemical, genome wide analyses, we annotated drug...
Abstract The molecular mechanisms that drive hematopoietic stem cell functional decline under conditions of telomere shortening are not completely understood. In light recent advances in single-cell technologies, we sought to redefine the transcriptional and epigenetic landscape mouse human cells attrition, as induced by pathogenic germline variants telomerase complex genes. Here, show attrition maintains persistent metabolic activation differentiation towards megakaryocytic lineage through...
Abstract The molecular mechanisms of venetoclax-based therapy failure in patients with acute myeloid leukemia were recently clarified, but the by which myelodysplastic syndromes (MDS) acquire secondary resistance to venetoclax after an initial response remain be elucidated. Here, we show expansion MDS hematopoietic stem cells (HSCs) a granulo-monocytic-biased transcriptional differentiation state who initially responded eventually relapsed. While HSCs undifferentiated cellular are sensitive...
Diarylheptanoids from Curcuma comosa, of the Zingiberaceae family, exhibit diverse estrogenic activities. In this study we investigated activity a major hydroxyl diarylheptanoid, 7-(3,4 -dihydroxyphenyl)-5-hydroxy-1-phenyl-(1E)-1-heptene (compound 092) isolated C. comosa. The compound elicited different transcriptional activities estrogen agonist at low concentrations (0.1–1 μM) and antagonist high (10–50 using luciferase reporter gene assay in HEK-293T cells. human breast cancer (MCF-7)...
RNA‐binding protein dysregulation and altered expression of proteins involved in the autophagy/proteasome pathway play a role many neurodegenerative disease onset/progression, including age‐related macular degeneration (AMD). HuR/ELAVL1 is master regulator gene human physiopathology. In ARPE‐19 cells exposed to proteasomal inhibitor MG132, HuR positively affects at posttranscriptional level p62 expression, stress response aggregate clearance with AMD. Here, we studied early effects...
Abstract SF3B1 mutations, which occur in 20% of patients with myelodysplastic syndromes (MDS), are the hallmarks a specific MDS subtype, ringed sideroblasts (MDS-RS), is characterized by accumulation erythroid precursors bone marrow and primarily affects elderly population. Here, using single-cell technologies functional validation studies primary SF3B1-mutant MDS-RS samples, we show that mutations lead to activation EIF2AK1 pathway response heme deficiency targeting this rescues aberrant...
Abstract DNA damage resistance is a major barrier to effective DNA-damaging therapy in multiple myeloma (MM). To discover mechanisms through which MM cells overcome damage, we investigate how become resistant antisense oligonucleotide (ASO) targeting Interleukin enhancer binding factor 2 (ILF2), regulator that overexpressed 70% of patients whose disease has progressed after standard therapies have failed. Here, show undergo adaptive metabolic rewiring restore energy balance and promote...
Nicotinamide phosphoribosyltransferase (NAMPT) is a key metabolic enzyme in NAD+ synthesis pathways and found upregulated several tumors, depicting NAD(H) lowering agents, like the NAMPT inhibitor FK866, as an appealing approach for anticancer therapy. Like other small molecules, FK866 triggers chemoresistance, observed cancer cellular models, which can prevent its clinical application. The molecular mechanisms sustaining acquired of resistance to were studied model triple negative breast...
// Natthakan Thongon 1, * , Ilaria Castiglioni 2, Chiara Zucal 1 Elisa Latorre Vito D'Agostino Inga Bauer 3 Michael Pancher 4 Alberto Ballestrero Georg Feldmann 5 Alessio Nencioni Alessandro Provenzani Laboratory of Genomic Screening, Centre for Integrative Biology, University Trento, Italy 2 Gene Expression and Muscular Dystrophy, San Raffaele Scientific Institute, Milan, Department Internal Medicine, Genoa, High Throughput Screening Facility, Pancreatic Cancer Translational Research,...
Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in NAD+ biosynthesis from nicotinamide, is one of major factors regulating cancer cells metabolism and considered a promising target for treating cancer. The prototypical NAMPT inhibitor FK866 effectively lowers levels cells, reducing activity NAD+-dependent enzymes, lowering intracellular ATP, promoting cell death. We show that induces translational arrest leukemia through inhibition MTOR/4EBP1 signaling initiation...
Gambogic acid (GA) has been reported to induce apoptosis in cholangiocarcinoma (CCA) cell lines. However, the molecular mechanisms underlying its anti-cancer activity remain poorly understood. This study was aimed investigate GA's effect on human CCA lines, KKU-M213 and HuCCA-1, associated Wnt/β-catenin signaling pathway.Cell viability, apoptosis, cycle analysis were conducted by MTT flow cytometry. The of GA mediated ER stress determined luciferase-reporter assay, qRT-PCR, western blot...
We investigated the effect of a phytoestrogen, (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (DPHD), from Curcuma comosa Roxb. (Zingiberaceae family) on adipogenic differentiation mesenchymal progenitors, human bone marrow-derived stem cells (hBMSCs). DPHD inhibited adipocyte hBMSCs by suppressing expression genes involved in adipogenesis. at concentrations 0.1, 1, and 10 μM significantly decreased triglyceride accumulation to 7.1 ± 0.2, 6.3 0.4, 4.9 0.2 mg/dL, respectively, compared...
Abstract The overexpression of the ecotropic viral integration site-1 gene ( EVI1/MECOM ) marks most lethal acute myeloid leukemia (AML) subgroup carrying chromosome 3q26 abnormalities. By taking advantage intersectionality high-throughput cell-based and expression screens selective pan-histone deacetylase inhibitors (HDACis) emerge as potent repressors EVI1 . To understand mechanism driving on-target anti-leukemia activity this compound class, here we dissect dynamics bone marrow cells...