A5041250508- Zebrafish Biomedical Research Applications
- Epigenetics and DNA Methylation
- Acute Myeloid Leukemia Research
- Hematopoietic Stem Cell Transplantation
- Immune Cell Function and Interaction
- Single-cell and spatial transcriptomics
- Immune cells in cancer
- Pancreatic function and diabetes
- Pregnancy and preeclampsia studies
- Pluripotent Stem Cells Research
- Mesenchymal stem cell research
- CAR-T cell therapy research
- Erythrocyte Function and Pathophysiology
- Aquaculture disease management and microbiota
- Cancer Genomics and Diagnostics
- Cancer, Hypoxia, and Metabolism
- Phagocytosis and Immune Regulation
- Liver physiology and pathology
- Reproductive System and Pregnancy
- CRISPR and Genetic Engineering
- Cancer-related gene regulation
- Renal and related cancers
- Hippo pathway signaling and YAP/TAZ
- Neonatal Respiratory Health Research
- Congenital heart defects research
Boston Children's Hospital
2007-2025
Boston Children's Museum
2018-2025
Children's Hospital
2025
Harvard University
2015-2024
Harvard Stem Cell Institute
2013-2023
Dana-Farber Cancer Institute
2007-2023
Beth Israel Deaconess Medical Center
2010-2020
Broad Institute
2020
Beth Israel Deaconess Hospital
2010-2015
Massachusetts General Hospital
2007-2012
Leukemia stem cells (LSCs) are capable of limitless self-renewal and responsible for the maintenance leukemia. Because selective eradication LSCs could offer substantial therapeutic benefit, there is interest in identifying signaling pathways that control their development. We studied mouse models acute myelogenous leukemia (AML) induced either by coexpression Hoxa9 Meis1a oncogenes or fusion oncoprotein MLL-AF9. show Wnt/beta-catenin pathway required derived from hematopoietic (HSC) more...
ABSTRACT Cbfa2 (AML1) encodes the DNA-binding subunit of a transcription factor in small family core-binding factors (CBFs). is required for differentiation all definitive hematopoietic cells, but not primitive erythropoiesis. Here we show that expressed progenitor and endothelial cells sites from which these are thought to emerge. Endothelial expressing yolk sac, vitelline umbilical arteries, ventral aspect dorsal aorta aorta/genital ridge/mesonephros (AGM) region. lining aorta, elsewhere...
Identifying signaling pathways that regulate hematopoietic stem and progenitor cell (HSPC) formation in the embryo will guide efforts to produce expand HSPCs ex vivo. Here we show sterile tonic inflammatory regulates embryonic HSPC formation. Expression profiling of progenitors with lymphoid potential cells (HSCs) from aorta/gonad/mesonephros (AGM) regions midgestation mouse embryos revealed a robust innate immune/inflammatory signature. Mouse lacking interferon γ (IFN-γ) or IFN-α zebrafish...
Polycomb repressive complex 2 (PRC2) silences genes through trimethylation of histone H3K27. PRC2 associates with numerous precursor messenger RNAs (pre-mRNAs) and long noncoding (lncRNAs) a binding preference for G-quadruplex RNA. In this work, we present 3.3-Å-resolution cryo–electron microscopy structure bound to Notably, RNA mediates the dimerization by both protomers inducing protein interface composed two copies catalytic subunit EZH2, thereby blocking nucleosome DNA interaction H3...
Acetaminophen (APAP) toxicity is the most common drug-induced cause of acute liver failure in United States. The only available treatment, N-acetylcysteine (NAC), has a limited time window efficacy, indicating need for additional therapeutic options. Zebrafish have emerged as powerful tool drug discovery. Here, we developed clinically relevant zebrafish model APAP toxicity. depleted glutathione stores, elevated aminotransferase levels, increased apoptosis, and caused dose-dependent...
Genetic mapping of mutations in model systems has facilitated the identification genes contributing to fundamental biological processes including human diseases. However, this approach historically required prior characterization informative markers. Here we report a fast and cost-effective method for genetic using next-generation sequencing that combines single nucleotide polymorphism discovery, mutation localization, potential causal sequence variants. In contrast approaches, have...
Vitamin D insufficiency is a worldwide epidemic affecting billions of individuals, including pregnant women and children. Despite its high incidence, the impact active vitamin D3 (1,25(OH)D3) on embryonic development beyond osteo-regulation remains largely undefined. Here, we demonstrate that 1,25(OH)D3 availability modulates zebrafish hematopoietic stem progenitor cell (HSPC) production. Loss Cyp27b1-mediated biosynthesis or receptor (VDR) function by gene knockdown resulted in...
Abstract A better understanding of the cell-fate transitions that occur in complex cellular ecosystems normal development and disease could inform cell engineering efforts lead to improved therapies. However, a major challenge is simultaneously identify new states, their transitions, elucidate gene expression dynamics governing cell-type diversification. Here, we present CellRouter, multifaceted single-cell analysis platform identifies cell-state transition trajectories by using flow...
The transcription factor Runx1 marks all functional hematopoietic stem cells (HSCs) in the embryo and is required for their generation. Mutations are found approximately 25% of acute leukemias familial platelet disorder, suggesting a role adult hematopoiesis as well. A comprehensive analysis expression lacking. Here we show that expressed HSCs mouse, well with spleen colony‐forming unit (CFU) culture CFU capacities. Additionally, document lineages at single cell level. majority myeloid...
The incidence of human papillary thyroid cancer (PTC) is increasing and an aggressive subtype this disease resistant to treatment with vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor. VEGFR2 promotes angiogenesis by triggering cell proliferation migration. However, the molecular mechanisms governing stability in vivo remain unknown. Additionally, whether influences PTC migration not clear. We show that ubiquitin E3 ligase SCFβ-TRCP ubiquitination destruction a casein kinase...