A5013639146- Epigenetics and DNA Methylation
- Acute Myeloid Leukemia Research
- Acute Lymphoblastic Leukemia research
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- Cancer Genomics and Diagnostics
- Pancreatic function and diabetes
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Metabolism and Genetic Disorders
- Single-cell and spatial transcriptomics
- Genetics and Neurodevelopmental Disorders
- Erythrocyte Function and Pathophysiology
- Renal and related cancers
- Hemoglobinopathies and Related Disorders
- 3D Printing in Biomedical Research
- Chromosomal and Genetic Variations
- CRISPR and Genetic Engineering
- Hippo pathway signaling and YAP/TAZ
- HER2/EGFR in Cancer Research
- Immune cells in cancer
- Protein purification and stability
- Plant Molecular Biology Research
- Hematopoietic Stem Cell Transplantation
- Monoclonal and Polyclonal Antibodies Research
- Neonatal Health and Biochemistry
St. Jude Children's Research Hospital
2024-2025
Children's Medical Center
2019-2023
The University of Texas Southwestern Medical Center
2019-2023
Abstract Epigenetic gene regulation and metabolism are highly intertwined, yet little is known about whether altered epigenetics influence cellular during cancer progression. Here, we show that EZH2 NRASG12D mutations cooperatively induce progression of myeloproliferative neoplasms to penetrant, transplantable, lethal myeloid leukemias in mice. EZH1, an homolog, indispensable for EZH2-deficient leukemia-initiating cells constitutes epigenetic vulnerability. BCAT1, which catalyzes the...
Biomolecular condensates participate in the regulation of gene transcription, yet relationship between nuclear condensation and transcriptional activation remains elusive. Here, we devised a biotinylated CRISPR-dCas9-based optogenetic method, light-activated macromolecular phase separation (LAMPS), to enable inducible formation, affinity purification, multiomic dissection at targeted genomic loci. LAMPS-induced enhancers promoters activates endogenous transcription by chromatin...
The formation of new red blood cells (RBC) (erythropoiesis) has served as a paradigm for understanding cellular differentiation and developmental control gene expression. metabolic regulation this complex, coordinated process remains poorly understood. Each step erythropoiesis, including lineage specification hematopoietic stem cells, proliferation, differentiation, terminal maturation into highly specialized oxygen-carrying unique requirements. Developing erythrocytes in mammals are also...
Metabolic requirements vary during development, and our understanding of how metabolic activity influences cell specialization is incomplete. Here, we describe a switch from glutamine catabolism to synthesis required for erythroid maturation. Glutamine synthetase (GS), one the oldest functioning genes in evolution, activated maturation detoxify ammonium generated heme biosynthesis, which up-regulated support hemoglobin production. Loss GS mouse precursors caused accumulation oxidative...
Recurrent IDH mutations catalyze NADPH-dependent production of oncometabolite R-2HG for tumorigenesis. inhibition provides clinical response in a subset acute myeloid leukemia (AML) cases; however, most patients develop resistance, highlighting the need more effective IDH-targeting therapies. By comparing transcriptomic alterations isogenic cells harboring CRISPR base-edited mutations, we identify activation adhesion molecules including CD44, transmembrane glycoprotein, as shared feature...
Mutations in IDH genes occur frequently acute myeloid leukemia (AML) and other human cancers to generate the oncometabolite R-2HG. Allosteric inhibition of mutant suppresses R-2HG production a subset patients with AML; however, acquired resistance emerges as new challenge, underlying mechanisms remain incompletely understood. Here we establish isogenic cells containing common oncogenic mutations by CRISPR base editing. By mutational scanning single amino acid variants base-edited cells,...
Osteolectin is a recently identified osteogenic growth factor that binds to Integrin α11 (encoded by Itga11), promoting Wnt pathway activation and differentiation bone marrow stromal cells. While Itga11 are not required for the formation of skeleton during fetal development, they maintenance adult mass. Genome-wide association studies in humans reported single-nucleotide variant (rs182722517) 16 kb downstream associated with reduced height plasma levels. In this study, we tested whether...
Abstract Cancers develop from the accumulation of somatic mutations, yet it remains unclear how oncogenic lesions cooperate to drive cancer progression. Using a mouse model harboring NRas G12D and EZH2 mutations that recapitulates leukemic progression, we employ single-cell transcriptomic profiling map cellular composition gene expression alterations in healthy or diseased bone marrows during leukemogenesis. At level, induces myeloid lineage-biased differentiation EZH2-deficiency impairs...
<p>Table S2 shows differentially expressed genes by RNA-seq</p>
<p>Table S4 shows key reagents and resources</p>
<p>Table S1 shows the list of genomic datasets</p>
<p>Table S5 shows transitions and parameters used for LC-MS</p>
<div>Abstract<p>Epigenetic gene regulation and metabolism are highly intertwined, yet little is known about whether altered epigenetics influence cellular during cancer progression. Here, we show that EZH2 NRAS<sup>G12D</sup> mutations cooperatively induce progression of myeloproliferative neoplasms to penetrant, transplantable, lethal myeloid leukemias in mice. EZH1, an homolog, indispensable for EZH2-deficient leukemia-initiating cells constitutes epigenetic...
<p>Supplementary Figures and Legends combined file contains 14 supplementary figures</p>
<p>Table S1 shows the list of genomic datasets</p>
<p>Table S3 shows sequences of primers and shRNAs</p>
<p>Table S3 shows sequences of primers and shRNAs</p>
<p>Table S5 shows transitions and parameters used for LC-MS</p>
<div>Abstract<p>Epigenetic gene regulation and metabolism are highly intertwined, yet little is known about whether altered epigenetics influence cellular during cancer progression. Here, we show that EZH2 NRAS<sup>G12D</sup> mutations cooperatively induce progression of myeloproliferative neoplasms to penetrant, transplantable, lethal myeloid leukemias in mice. EZH1, an homolog, indispensable for EZH2-deficient leukemia-initiating cells constitutes epigenetic...
<p>Table S2 shows differentially expressed genes by RNA-seq</p>