Felipe Beckedorff
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View article: Co-targeting menin and LSD1 dismantles oncogenic programs and restores differentiation in MLL-rearranged AML
Co-targeting menin and LSD1 dismantles oncogenic programs and restores differentiation in MLL-rearranged AML Open
Acute myeloid leukemia (AML) harboring MLL ( MLL1, KMT2A ) rearrangement ( MLL-r ) remains a lethal subtype with limited durable responses to single-agent menin inhibition. To define rational combination strategies, we performed a high-thr…
View article: Balancing Activation and Repression: CoREST-p300 Antagonism Controls Retinoic Acid-Driven Differentiation in AML
Balancing Activation and Repression: CoREST-p300 Antagonism Controls Retinoic Acid-Driven Differentiation in AML Open
The histone demethylase KDM1A (LSD1), a component of the CoREST corepressor complex, is highly expressed in hematologic malignancies and regulates hematopoietic differentiation. Despite its essential developmental role, LSD1 inhibition has…
View article: Retinoic acid and ascorbate synergize to suppress myeloid leukemia via TET2 activation
Retinoic acid and ascorbate synergize to suppress myeloid leukemia via TET2 activation Open
Enhancing ten-eleven translocation 2 (TET2) activity through genetic or pharmacologic approaches, such as ascorbate supplementation, can slow myeloid malignancy progression. However, ascorbate alone may be insufficient to fully activate TE…
View article: The MLLT3 YEATS domain is a dual reader of histone marks (H3K9/18/27ac/cr) and ncRNA (7SK), linking epigenetic and RNA signaling to regulate hematopoiesis
The MLLT3 YEATS domain is a dual reader of histone marks (H3K9/18/27ac/cr) and ncRNA (7SK), linking epigenetic and RNA signaling to regulate hematopoiesis Open
Summary The protein MLLT3 (AF9) is a critical regulator of hematopoiesis. The N-terminal YEATS domain of MLLT3 is an epigenetic reader that binds to acetylated as well as crotonylated lysine. Using PAR-CLIP, biochemical assays, and NMR bas…
View article: B12 promotes gut dysbiosis and an inflammatory microenvironment that potentiates <i>Tet2</i>-deficient hematopoiesis
B12 promotes gut dysbiosis and an inflammatory microenvironment that potentiates <i>Tet2</i>-deficient hematopoiesis Open
Recent studies have linked elevated vitamin B12 serum levels with the presence of clonal hematopoiesis (CH) and an increased risk of developing myeloid malignancy. High B12 supplementation increases serum levels, alters gut microbial compo…
View article: TAF1 is required for fetal but not adult hematopoiesis in mice
TAF1 is required for fetal but not adult hematopoiesis in mice Open
While many sequence-specific transcription factors (TFs) have been identified as key regulators of hematopoietic stem cell (HSC) lineage determination, the function of general TFs in HSC behavior is poorly understood. To evaluate the funct…
View article: Bypass of Blocking Lesions by RNAPII Impairs the Transcriptional DNA Damage Response
Bypass of Blocking Lesions by RNAPII Impairs the Transcriptional DNA Damage Response Open
Ultraviolet (UV) irradiation and platinum-based drugs generate bulky DNA lesions that impede transcription elongation by RNA Polymerase II (RNAPII). This transcriptional block triggers a coordinated stress response involving transcription-…
View article: Tetrameric INTS6-SOSS1 complex facilitates DNA:RNA hybrid autoregulation at double-strand breaks
Tetrameric INTS6-SOSS1 complex facilitates DNA:RNA hybrid autoregulation at double-strand breaks Open
DNA double-strand breaks (DSBs) represent a lethal form of DNA damage that can trigger cell death or initiate oncogenesis. The activity of RNA polymerase II (RNAPII) at the break site is required for efficient DSB repair. However, the regu…
View article: Altered RNA export by SF3B1 mutants confers sensitivity to nuclear export inhibition
Altered RNA export by SF3B1 mutants confers sensitivity to nuclear export inhibition Open
View article: Enhancing Transcriptome Mapping with Rapid PRO-seq Profiling of Nascent RNA
Enhancing Transcriptome Mapping with Rapid PRO-seq Profiling of Nascent RNA Open
Precision nuclear run-on (PRO) sequencing (PRO-seq) is a powerful technique for mapping polymerase active sites with nucleotide resolution and measuring newly synthesized transcripts at both promoters and enhancer elements. The current PRO…
View article: Tetrameric INTS6-SOSS1 complex facilitates DNA:RNA hybrid autoregulation at double-strand breaks
Tetrameric INTS6-SOSS1 complex facilitates DNA:RNA hybrid autoregulation at double-strand breaks Open
DNA double strand breaks (DSBs) represent a lethal form of DNA damage that can trigger cell death and initiate oncogenesis. The activity of RNA polymerase II (RNAPII) at the break site is required for efficient DSB repair. However, the reg…
View article: Ecto-CD38-NADase inhibition modulates cardiac metabolism and protects mice against doxorubicin-induced cardiotoxicity
Ecto-CD38-NADase inhibition modulates cardiac metabolism and protects mice against doxorubicin-induced cardiotoxicity Open
Aims Doxorubicin (DXR) is a chemotherapeutic agent that causes dose-dependent cardiotoxicity. Recently, it has been proposed that the NADase CD38 may play a role in doxorubicin-induced cardiotoxicity (DIC). CD38 is the main NAD+-catabolizi…
View article: Single-nucleus RNA sequencing of developing superior colliculus identifies neuronal diversity and candidate mediators of circuit assembly
Single-nucleus RNA sequencing of developing superior colliculus identifies neuronal diversity and candidate mediators of circuit assembly Open
View article: Single-Nucleus RNA Sequencing of Developing and Mature Superior Colliculus Identifies Neuronal Diversity and Candidate Mediators of Circuit Assembly
Single-Nucleus RNA Sequencing of Developing and Mature Superior Colliculus Identifies Neuronal Diversity and Candidate Mediators of Circuit Assembly Open
The superior colliculus (SC) is a sensorimotor structure in the midbrain that integrates input from multiple sensory modalities to initiate motor commands. It undergoes well-characterized steps of circuit assembly during development, rende…
View article: The SWI/SNF chromatin-remodeling subunit DPF2 facilitates NRF2-dependent antiinflammatory and antioxidant gene expression
The SWI/SNF chromatin-remodeling subunit DPF2 facilitates NRF2-dependent antiinflammatory and antioxidant gene expression Open
During emergency hematopoiesis, hematopoietic stem cells (HSCs) rapidly proliferate to produce myeloid and lymphoid effector cells, a response that is critical against infection or tissue injury. If unresolved, this process leads to sustai…
View article: Data from Protein Kinase D–Dependent Downregulation of Immediate Early Genes through Class IIA Histone Deacetylases in Acute Lymphoblastic Leukemia
Data from Protein Kinase D–Dependent Downregulation of Immediate Early Genes through Class IIA Histone Deacetylases in Acute Lymphoblastic Leukemia Open
Acute lymphoblastic leukemia (ALL) is a leading cause of cancer-related death in children and adolescents, and cure rates for relapsed/refractory ALL remain dismal, highlighting the need for novel targeted therapies. To identify genome-wid…
View article: Data from Protein Kinase D–Dependent Downregulation of Immediate Early Genes through Class IIA Histone Deacetylases in Acute Lymphoblastic Leukemia
Data from Protein Kinase D–Dependent Downregulation of Immediate Early Genes through Class IIA Histone Deacetylases in Acute Lymphoblastic Leukemia Open
Acute lymphoblastic leukemia (ALL) is a leading cause of cancer-related death in children and adolescents, and cure rates for relapsed/refractory ALL remain dismal, highlighting the need for novel targeted therapies. To identify genome-wid…
View article: Supplementary Table 1, Supplemental Figures 1-5 from Protein Kinase D–Dependent Downregulation of Immediate Early Genes through Class IIA Histone Deacetylases in Acute Lymphoblastic Leukemia
Supplementary Table 1, Supplemental Figures 1-5 from Protein Kinase D–Dependent Downregulation of Immediate Early Genes through Class IIA Histone Deacetylases in Acute Lymphoblastic Leukemia Open
Supplementary Table 1. Antibodies used in the study Figure S1. AICAR-induced downregulation of IEGs mRNA expression in ALL cells. Figure S2. The mechanism of AICAR-induced IEGs downregulation is AMPK-independent. Figure S3. The PKC inhibit…
View article: Supplementary Table 1, Supplemental Figures 1-5 from Protein Kinase D–Dependent Downregulation of Immediate Early Genes through Class IIA Histone Deacetylases in Acute Lymphoblastic Leukemia
Supplementary Table 1, Supplemental Figures 1-5 from Protein Kinase D–Dependent Downregulation of Immediate Early Genes through Class IIA Histone Deacetylases in Acute Lymphoblastic Leukemia Open
Supplementary Table 1. Antibodies used in the study Figure S1. AICAR-induced downregulation of IEGs mRNA expression in ALL cells. Figure S2. The mechanism of AICAR-induced IEGs downregulation is AMPK-independent. Figure S3. The PKC inhibit…
View article: The Integrator complex regulates microRNA abundance through RISC loading
The Integrator complex regulates microRNA abundance through RISC loading Open
MicroRNA (miRNA) homeostasis is crucial for the posttranscriptional regulation of their target genes during development and in disease states. miRNAs are derived from primary transcripts and are processed from a hairpin precursor intermedi…
View article: Single-Nucleus RNA Sequencing of Developing and Mature Superior Colliculus Identifies Neuronal Diversity and Candidate Mediators of Circuit Assembly
Single-Nucleus RNA Sequencing of Developing and Mature Superior Colliculus Identifies Neuronal Diversity and Candidate Mediators of Circuit Assembly Open
Summary The superior colliculus (SC) is a sensorimotor structure in the midbrain that integrates input from multiple sensory modalities to initiate motor commands. It undergoes well-characterized steps of circuit assembly during developmen…
View article: Endogenous metabolism in endothelial and immune cells generates most of the tissue vitamin B3 (nicotinamide)
Endogenous metabolism in endothelial and immune cells generates most of the tissue vitamin B3 (nicotinamide) Open
View article: Retinal ganglion cell expression of cytokine enhances occupancy of NG2 cell-derived astrocytes at the nerve injury site: Implication for axon regeneration
Retinal ganglion cell expression of cytokine enhances occupancy of NG2 cell-derived astrocytes at the nerve injury site: Implication for axon regeneration Open
View article: Integrator enforces the fidelity of transcriptional termination at protein-coding genes
Integrator enforces the fidelity of transcriptional termination at protein-coding genes Open
Integrator directly binds and terminates protein-coding transcripts enriched in alternative polyadenylation sequences.
View article: Identification of long noncoding RNAs in injury-resilient and injury-susceptible mouse retinal ganglion cells
Identification of long noncoding RNAs in injury-resilient and injury-susceptible mouse retinal ganglion cells Open
View article: The Integrator complex regulates microRNA abundance through RISC loading
The Integrator complex regulates microRNA abundance through RISC loading Open
MicroRNA (miRNA) homeostasis is crucial for the post-transcriptional regulation of their target genes and miRNA dysregulation has been linked to multiple diseases, including cancer. The molecular mechanisms underlying miRNA biogenesis from…
View article: Protein Kinase D–Dependent Downregulation of Immediate Early Genes through Class IIA Histone Deacetylases in Acute Lymphoblastic Leukemia
Protein Kinase D–Dependent Downregulation of Immediate Early Genes through Class IIA Histone Deacetylases in Acute Lymphoblastic Leukemia Open
Acute lymphoblastic leukemia (ALL) is a leading cause of cancer-related death in children and adolescents, and cure rates for relapsed/refractory ALL remain dismal, highlighting the need for novel targeted therapies. To identify genome-wid…
View article: Identification of Long Noncoding RNAs in Distinct Subtypes of Mouse Retinal Ganglion Cells&nbsp;
Identification of Long Noncoding RNAs in Distinct Subtypes of Mouse Retinal Ganglion Cells Open
Background : Emerging evidence indicates that long noncoding RNAs (lncRNAs) are important regulators of various biological processes, and their expression can be altered following certain pathological conditions, including central nervous …
View article: PVT1 signals an androgen-dependent transcriptional repression program in prostate cancer cells and a set of the repressed genes predicts high-risk tumors
PVT1 signals an androgen-dependent transcriptional repression program in prostate cancer cells and a set of the repressed genes predicts high-risk tumors Open
View article: Additional file 2 of Identification of long noncoding RNAs in injury-resilient and injury-susceptible mouse retinal ganglion cells
Additional file 2 of Identification of long noncoding RNAs in injury-resilient and injury-susceptible mouse retinal ganglion cells Open
Additional file 2: Table S2. List of lncRNAs detected in ipRGCs and ooDSGCs.