A5023457020- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- DNA Repair Mechanisms
- Cancer-related gene regulation
- CRISPR and Genetic Engineering
- Single-cell and spatial transcriptomics
- RNA Research and Splicing
- Congenital heart defects research
- Atherosclerosis and Cardiovascular Diseases
- RNA and protein synthesis mechanisms
- Chromosomal and Genetic Variations
- Prostate Cancer Treatment and Research
- Cancer-related molecular mechanisms research
- Immune cells in cancer
- Adipose Tissue and Metabolism
- Zebrafish Biomedical Research Applications
- Fungal and yeast genetics research
- Cancer Genomics and Diagnostics
- Phagocytosis and Immune Regulation
- Genetics and Neurodevelopmental Disorders
- Histone Deacetylase Inhibitors Research
- Lung Cancer Treatments and Mutations
- Ubiquitin and proteasome pathways
- Angiogenesis and VEGF in Cancer
Harvard University
2021-2025
Boston Children's Hospital
2021-2025
Houston Methodist
2016-2025
Cornell University
1990-2025
Methodist Hospital
2016-2025
Dana-Farber/Harvard Cancer Center
2022-2024
Broad Institute
2022-2024
Weill Cornell Medicine
1990-2024
Boston Children's Museum
2022-2024
Lemuel Shattuck Hospital
2024
Recent developments in next-generation sequencing have enabled whole-genome profiling of nucleosome organizations. Although several algorithms for inferring position from a single experimental condition been available, it remains challenge to accurately define dynamic nucleosomes associated with environmental changes. Here, we report comprehensive bioinformatics pipeline, DANPOS, explicitly designed analysis at single-nucleotide resolution. Using both simulated and real data, demonstrated...
Background Date palm (Phoenix dactylifera L.), a member of Arecaceae family, is one the three major economically important woody palms—the two other palms being oil and coconut tree—and its fruit staple food among Middle East North African nations, as well many tropical subtropical regions. Here we report complete sequence data chloroplast (cp) genome based on pyrosequencing. Methodology/Principal Findings After extracting 369,022 cp sequencing reads from our whole-genome-shotgun data, put...
All eukaryotic cells divide a finite number of times, although the mechanistic basis this replicative aging remains unclear. Replicative is accompanied by reduction in histone protein levels, and cause budding yeast. Here we show that nucleosome occupancy decreased 50% across whole genome during using spike-in controlled micrococcal nuclease digestion followed sequencing. Furthermore, nucleosomes became less well positioned or moved to sequences predicted better accommodate octamers. The...
Date palm (Phoenix dactylifera L.) is a cultivated woody plant species with agricultural and economic importance. Here we report genome assembly for an elite variety (Khalas), which 605.4 Mb in size covers >90% of the (~671 Mb) >96% its genes (~41,660 genes). Genomic sequence analysis demonstrates that P. experienced clear genome-wide duplication after either ancient whole duplications or massive segmental duplications. Genetic diversity indicates stress resistance sugar metabolism-related...
Significance Decades of research have not deciphered the mechanism by which methyl-CpG binding protein 2 (MeCP2) regulates transcription and why Rett symptoms manifest 1 to y after birth. We hypothesized that temporal dynamics MeCP2 might provide an answer. developed mice with EGFP-tagged allele identify high-resolution profiles in adult mouse brain. Using genomic profiles, methylation maps, mRNA deep-sequencing data, we found binds non-CG (mCH, mCG) regulate expression genes altered models...
Genome-wide analyses of changes in gene expression, transcription factor occupancy on DNA, histone modification patterns chromatin, genomic copy number variation, and nucleosome positioning have become popular many modern laboratories, yielding a wealth information during health disease states. However, most these studies overlooked an inherent normalization problem that must be corrected with spike-in controls. Here we describe the reason why controls are so important explain how to...
Smooth muscle cell (SMC) phenotypic switching has been increasingly detected in aortic aneurysm and dissection (AAD) tissues. However, the diverse SMC phenotypes AAD tissues mechanisms driving alterations remain to be identified.
Cancers have long been recognized to be not only genetically but also epigenetically distinct from their tissues of origin. Although genetic alterations underlying oncogene upregulation well studied, what extent epigenetic mechanisms, such as DNA methylation, can induce expression remains unknown.
Hypercholesterolemia, the driving force of atherosclerosis, accelerates expansion and mobilization hematopoietic stem progenitor cells (HSPCs). The molecular determinants connecting hypercholesterolemia with hematopoiesis are unclear. Here, we report that a somite-derived prohematopoietic cue, AIBP, orchestrates HSPC emergence from hemogenic endothelium, type specialized endothelium manifesting potential. Mechanistically, AIBP-mediated cholesterol efflux activates endothelial Srebp2, master...
Naive CD4+ T cells can be converted to Foxp3+ regulatory (Tregs) in the periphery (iTregs), where induction of Foxp3 gene expression is central Treg differentiation. OX40 signaling known inhibit and induction, but underlying mechanisms remain poorly defined. Here, we found that costimulation activates two distinct molecular pathways suppress freshly activated naive cells. Specifically, upregulates BATF3 BATF, which produce a closed chromatin configuration repress Sirt1/7-dependent manner....
DNA replication-coupled nucleosome assembly is essential to maintain genome integrity and retain epigenetic information. Multiple involved histone chaperones have been identified, but how coupled replication remains elusive. Here we show that protein A (RPA), an replisome component binds single-stranded DNA, has a role in assembly. RPA directly free H3-H4. Assays using synthetic sequence mimics freshly unwound at fork showed promotes DNA-(H3-H4) complex formation immediately adjacent...
Epsin endocytic adaptor proteins are implicated in the progression of atherosclerosis; however, underlying molecular mechanisms have not yet been fully defined. In this study, we determined how epsins enhance endothelial-to-mesenchymal transition (EndoMT) atherosclerosis and assessed efficacy a therapeutic peptide preclinical model disease.
Understanding the role of a given transcription factor (TF) in regulating gene expression requires precise mapping its binding sites genome. Chromatin immunoprecipitation-exo, an emerging technique using λ exonuclease to digest TF unbound DNA after ChIP, is designed reveal site (TFBS) boundaries with near-single nucleotide resolution. Although ChIP-exo promises deeper insights into regulation, no dedicated bioinformatics tool exists leverage advantages. Most ChIP-seq and ChIP-chip analytic...
BMI1, a polycomb group (PcG) protein, plays critical role in epigenetic regulation of cell differentiation and proliferation, cancer stem self-renewal. BMI1 is upregulated multiple types cancer, including prostate cancer. As key component repressive complex 1 (PRC1), exerts its oncogenic functions by enhancing the enzymatic activities RING1B to ubiquitinate histone H2A at lysine 119 repress gene transcription. Here, we report PRC1-independent that for castration-resistant (CRPC) progression....
Translational efficiency correlates with longevity, yet its role in lifespan determination remains unclear. Using ribosome profiling, translation is globally reduced during replicative aging budding yeast by at least two mechanisms: Firstly, Ssd1 induced aging, sequestering mRNAs to P-bodies. Furthermore, overexpression young cells and extended lifespan, while loss of the translational deficit old shortened lifespan. Secondly, phosphorylation eIF2α, mediated stress kinase Gcn2, was elevated...