A5048333738- MicroRNA in disease regulation
- Acute Myeloid Leukemia Research
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Mitochondrial Function and Pathology
- Autophagy in Disease and Therapy
- RNA modifications and cancer
- ATP Synthase and ATPases Research
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Cancer-related Molecular Pathways
- Metal complexes synthesis and properties
- DNA Repair Mechanisms
- Cancer Treatment and Pharmacology
- Photosynthetic Processes and Mechanisms
- Nitric Oxide and Endothelin Effects
- Animal Genetics and Reproduction
- Cancer, Hypoxia, and Metabolism
- CRISPR and Genetic Engineering
- Metabolomics and Mass Spectrometry Studies
- Metabolism and Genetic Disorders
- RNA Interference and Gene Delivery
- Cytokine Signaling Pathways and Interactions
- HIV/AIDS drug development and treatment
- RNA Research and Splicing
Rutgers, The State University of New Jersey
2023-2025
Veneto Institute of Molecular Medicine
2016-2025
Johnson University
2024
New York University
2019-2023
NYU Langone Health
2019-2023
University of Padua
2016-2022
NYU Langone’s Laura and Isaac Perlmutter Cancer Center
2020
Fondazione Santa Lucia
2016
Istituti di Ricovero e Cura a Carattere Scientifico
2016
Dulbecco Telethon Institute
2016
Abstract The BCL2 family plays important roles in acute myeloid leukemia (AML). Venetoclax, a selective inhibitor, has received FDA approval for the treatment of AML. However, drug resistance ensues after prolonged treatment, highlighting need greater understanding underlying mechanisms. Using genome-wide CRISPR/Cas9 screen human AML, we identified genes whose inactivation sensitizes AML blasts to venetoclax. Genes involved mitochondrial organization and function were significantly depleted...
The mitochondrial contact site and cristae organizing system (MICOS) Optic atrophy 1 (OPA1) control shape, thus affecting function apoptosis. Whether how they physically functionally interact is unclear. Here, we provide evidence that OPA1 epistatic to MICOS in the regulation of shape. Proteomic analysis identifies multiple components native OPA1-containing high molecular weight complexes disrupted during remodeling. MIC60, a core protein, interacts with OPA1, together, junction number...
Abstract It is unclear how the mitochondrial fusion protein Optic atrophy 1 (OPA1), which inhibits cristae remodeling, protects from dysfunction. Here we identify F o -ATP synthase as effector of OPA1 in protection. In overexpressing cells, loss proton electrochemical gradient caused by respiratory chain complex III inhibition blunted and this protection abolished ATP inhibitor oligomycin. Mechanistically, can interact, but recombinant fails to promote oligomerization purified reconstituted...
Abstract BH3 mimetics are used as an efficient strategy to induce cell death in several blood malignancies, including acute myeloid leukemia (AML). Venetoclax, a potent BCL-2 antagonist, is clinically combination with hypomethylating agents for the treatment of AML. Moreover, MCL1 or dual BCL-2/BCL-xL antagonists under investigation. Yet, resistance single combinatorial BH3-mimetic therapies eventually ensues. Integration multiple genome-wide CRISPR/Cas9 screens revealed that loss mitophagy...
Abstract Background Genomic instability promotes evolution and heterogeneity of tumors. Unraveling its mechanistic basis is essential for the design appropriate therapeutic strategies. In a previous study, we reported an unexpected oncogenic property p21 WAF1/Cip1 , showing that chronic expression in p53-deficient environment causes genomic by deregulation replication licensing machinery. Results We now demonstrate can further fuel suppressing repair capacity low- high-fidelity pathways deal...
Telomeres are composed of TTAGGG repeats and located at the ends chromosomes. protect chromosomes from instability in mammals, including mice humans. Repetitive sequences also found intrachromosomal sites, where they named as interstitial telomeric (ITSs). Aberrant ITSs implicated chromosomal cancer cells. Interestingly, pigs, vertebrate telomere (vITSs) localized centromeric region chromosome 6, addition to end all Surprisingly, we that botanic sequences, TTTAGGG (bITSs), localize with...
<p>Supplementary Methods, Tables, and References</p>
<p>Supplementary Methods, Tables, and References</p>
<div>Abstract<p>BH3-mimetics are used as an efficient strategy to induce cell death in several blood malignancies, including acute myeloid leukemia (AML). Venetoclax, a potent BCL-2 antagonist, is clinically combination with hypomethylating agents for the treatment of AML. Moreover, MCL-1 or dual BCL-2/BCL-xL antagonists under investigation. Yet, resistance single combinatorial BH3-mimetics therapies eventually ensues. Integration multiple genome-wide CRISPR/Cas9 screens revealed...
<p>Supplemental Figure S1 shows the integration of CRISPR/Cas9 loss-of-function screens to identify dependencies and liabilities in BH3-mimetics treatments. Supplemental S2 demonstrates that increased mitochondria-ER interactions contribute resistance. S3 mitophagy affects responsiveness AML cells BH3-mimetics. S4 reveals enhanced autophagic clearance mitochondria as a mechanism resistance AML. S5 exhibits synergism between macroautophagy inhibition human S6 deletion MFN2 or MARCH5...
<p>Supplemental Figure S1 shows the integration of CRISPR/Cas9 loss-of-function screens to identify dependencies and liabilities in BH3-mimetics treatments. Supplemental S2 demonstrates that increased mitochondria-ER interactions contribute resistance. S3 mitophagy affects responsiveness AML cells BH3-mimetics. S4 reveals enhanced autophagic clearance mitochondria as a mechanism resistance AML. S5 exhibits synergism between macroautophagy inhibition human S6 deletion MFN2 or MARCH5...