A5101873101- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- RNA Research and Splicing
- RNA modifications and cancer
- Pluripotent Stem Cells Research
- Plant Disease Resistance and Genetics
- Zebrafish Biomedical Research Applications
- DNA Repair Mechanisms
- CAR-T cell therapy research
- Hematopoietic Stem Cell Transplantation
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Protein Degradation and Inhibitors
- Mesenchymal stem cell research
- CRISPR and Genetic Engineering
- Viral Infectious Diseases and Gene Expression in Insects
- Acute Lymphoblastic Leukemia research
- CNS Lymphoma Diagnosis and Treatment
- Histone Deacetylase Inhibitors Research
- Ubiquitin and proteasome pathways
- Fungal and yeast genetics research
- Lymphoma Diagnosis and Treatment
- Molecular Biology Techniques and Applications
- Mass Spectrometry Techniques and Applications
Boston Children's Hospital
2016-2025
Boston Children's Museum
2016-2025
Harvard University
2017-2021
Dana-Farber Cancer Institute
2017-2021
Family Research Institute
2018
University of North Carolina at Chapel Hill
2014-2017
Boston University
2017
Harvard Stem Cell Institute
2017
Segeberger Kliniken
2016
UNC Lineberger Comprehensive Cancer Center
2016
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 YEATS domain, found in a number of chromatin-associated proteins, has recently been shown to have the capacity bind histone lysine acetylation. Here, we show that domain Taf14, member key transcriptional and chromatin-modifying complexes yeast, is selective reader H3 Lys9 acetylation (H3K9ac). Structural analysis reveals acetylated sandwiched an aromatic cage formed by F62 W81. Disruption this binding cells impairs gene transcription DNA damage response. Our findings establish highly...
Co-transcriptional splicing takes place in the context of a highly dynamic chromatin architecture, yet role restructuring coordinating transcription with RNA has not been fully resolved. To further define contribution histone modifications to pre-mRNA Saccharomyces cerevisiae, we probed library point mutants using reporter monitor splicing. We found that mutation H3 lysine 36 (H3K36) – residue methylated by Set2 during elongation exhibited phenotypes similar those mutants. identified genetic...
ABSTRACT Genes involved in the regulation of chromatin structure are frequently disrupted cancer, contributing to an aberrant transcriptome and phenotypic plasticity. Yet, therapeutics targeting mutant forms chromatin-modifying enzymes have yielded only modest clinical utility, underscoring difficulty epigenomic underpinnings gene regulatory networks. Here, we sought identify novel epigenetic vulnerabilities diffuse large B-cell lymphoma (DLBCL). Through screens biochemical analysis,...
Leukemia phenotypes vary with age of onset. Delineating mechanisms specificity in leukemia could improve disease models and uncover new therapeutic approaches. Here, we used heterochronic transplantation driven by MLL/KMT2A translocations to investigate the contribution hematopoietic microenvironment age-specific phenotypes. When MLL-AF9, cells adult sustained a myeloid phenotype, whereas neonatal supported genesis mixed early B cell/myeloid leukemia. In MLL-ENL leukemia, potentiated...
High expression of LIN28B is associated with aggressive malignancy and poor survival. Here, probing MYCN-amplified neuroblastoma as a model system, we showed that was enhanced cell migration in vitro invasive metastatic behavior murine xenografts. Sequence analysis the polyribosome fraction LIN28B-expressing cells revealed let-7–independent enrichment transcripts encoding components translational ribosomal apparatus depletion neuronal developmental programs. We further observed utilizes both...
Methylation of histone H3 lysine 36 (H3K36me) by yeast Set2 is critical for the maintenance chromatin structure and transcriptional fidelity. However, we do not know full range Set2/H3K36me functions or scope mechanisms that regulate Set2-dependent H3K36 methylation. Here, show APC/CCDC20 complex regulates protein abundance during cell cycle. Significantly, absence Set2-mediated H3K36me causes a loss cycle control pronounced defects in fidelity regulatory genes, class genes are generally...
H2A.Z is a histone H2A variant that contributes to transcriptional regulation, DNA damage response and limits heterochromatin spreading. In Saccharomyces cerevisiae, deposited by the SWR-C complex, which relies on several chaperones including Nap1 Chz1 deliver H2A.Z-H2B dimers SWR-C. However, mechanisms cooperate bind their contribution deposition in chromatin not well understood. Using structural modeling molecular dynamics simulations, we identify series of residues form chaperone-specific...
Studies of hematopoietic stem cell (HSC) development from pre-HSC-producing hemogenic endothelial cells (HECs) are hampered by the rarity these and presence other types with overlapping marker expression profiles. We generated a Tg(Runx1-mKO2; Ly6a-GFP) dual reporter mouse to visualize commitment study pre-HSC emergence maturation. Runx1-mKO2 marked all intra-arterial HECs cluster (HCCs), including pre-HSCs, myeloid- lymphoid progenitors, HSCs themselves. However, HSC potential were almost...
Intravascular lymphoma (IVL) is a rare extra nodal variant of non Hodgkin's characterised by neoplastic lymphoid cells growing inside the lumina medium and small vessels. IVL limited to central nervous system (CNS) an extremely condition as usually found with systemic lesions. Most cases are not diagnosed until post mortem because variable clinical presentation non-specific laboratory findings. Even if early disease clinically aggressive fatal, even detection treatment. We present case...