A5056279051- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Cancer Immunotherapy and Biomarkers
- Gene Regulatory Network Analysis
- Pluripotent Stem Cells Research
- Pancreatic and Hepatic Oncology Research
- Phagocytosis and Immune Regulation
- Heat shock proteins research
- Single-cell and spatial transcriptomics
- Molecular Biology Techniques and Applications
- Mechanisms of cancer metastasis
- Peptidase Inhibition and Analysis
- CRISPR and Genetic Engineering
- Advanced Electron Microscopy Techniques and Applications
- thermodynamics and calorimetric analyses
- Adipose Tissue and Metabolism
- Genomics and Phylogenetic Studies
- Force Microscopy Techniques and Applications
- Cancer Genomics and Diagnostics
- Advanced Fluorescence Microscopy Techniques
- Plant Molecular Biology Research
- Genetics, Aging, and Longevity in Model Organisms
- Cancer Mechanisms and Therapy
Massachusetts Institute of Technology
2018-2024
Cornell University
2015-2021
Koch Institute for Integrative Cancer Research At MIT
2021
Allen Institute
2021
Pediatrics and Genetics
2019
Institute for Systems Biology
2019
University of Connecticut
2019
University of Maryland, Baltimore
2012
Abstract Transcription is the primary regulatory step in gene expression. Divergent transcription initiation from promoters and enhancers produces stable RNAs genes unstable 1,2 . Nascent RNA capture sequencing assays simultaneously measure enhancer activity cell populations 3 However, fundamental questions about temporal regulation of enhancer–gene coordination remain unanswered, primarily because absence a single-cell perspective on active transcription. In this study, we present...
Abstract Programs of gene expression are executed by a battery transcription factors that coordinate divergent from pair tightly linked core initiation regions promoters and enhancers. Here, to investigate how is reprogrammed upon stress, we measured nascent RNA synthesis at nucleotide-resolution, profiled histone H4 acetylation in human cells. Our results globally show the release promoter-proximal paused polymerase into elongation functions as critical switch which gene’s response stress...
The coordinated regulation of gene expression at the transcriptional level is fundamental to development and homeostasis. Inducible systems are invaluable when studying transcription because regulatory process can be triggered instantaneously, allowing tracking ordered mechanistic events. Here, we use precision run-on sequencing (PRO-seq) examine genome-wide heat shock (HS) response in Drosophila function two key factors on immediate activation or repression all genes regulated by HS. We...
Abstract Tracking active transcription with the nuclear run-on (NRO) assays has been instrumental in uncovering mechanisms of gene regulation. The coupling NROs high-throughput sequencing facilitated discovery previously unannotated or undetectable RNA classes genome-wide. Precision (PRO-seq) is a variant that maps polymerase sites nucleotide near-nucleotide resolution. One main drawback to this and many other nascent detection methods somewhat intimidating multi-day workflow associated...
Gene expression heterogeneity underlies cell states and contributes to developmental robustness. While can arise from stochastic transcriptional processes, the extent which it is regulated unclear. Here, we characterize regulatory program underlying in murine embryonic stem (mESC) states. We identify differentially active transcribed enhancers (DATEs) across DATEs regulate expressed genes are distinguished by co-binding of transcription factors Klf4 Zfp281. In contrast other that interact a...
Heat shock response (HSR) maintains and restores protein homeostasis when cells are exposed to proteotoxic heat stress. (HS) triggers a rapid robust change in genome-wide transcription, synthesis, chaperone activity; therefore, the HSR has been widely used as model system these studies. The conventional method of performing instantaneous HS laboratory uses heated fresh media induce added cells. However, addition may evoke additional cellular responses signaling pathways. Here, we compared...
The serine/threonine kinase Pim-1 directs selected signaling events that promote cell growth and survival is overexpressed in diverse human cancers. expression tightly controlled through multiple mechanisms, including regulation of mRNA turnover. In several cultured models, mitogenic stimulation rapidly induced stabilized PIM1 mRNA, however, vigorous destabilization 4-6 hours later helped restore basal levels. Acceleration turnover coincided with accumulation tristetraprolin (TTP), an...
Abstract Transcription is the primary regulatory step in gene expression. Divergent transcription initiation from promoters and enhancers produces stable RNAs genes unstable 1–5 . Nascent RNA capture sequencing assays simultaneously measure enhancer activity cell populations 6–9 However, fundamental questions temporal regulation of enhancer-gene synchrony remain unanswered primarily due to absence a single-cell perspective on active transcription. In this study, we present scGRO-seq - novel...
Abstract The coordinated regulation of gene expression at the transcriptional level is fundamental to organismal development and homeostasis. Inducible systems are invaluable when studying transcription because regulatory process can be triggered instantaneously, allowing tracking ordered mechanistic events. Here, we use Precision Run-On sequencing (PRO-seq) examine genome-wide Heat Shock (HS) response in Drosophila function two key factors on immediate activation or repression all genes...
Abstract Pancreatic ductal Adenocarcinoma (PDAC) is an aggressive malignancy complicated by poor early diagnosis and a lack of response to traditional treatments. It characterized desmoplastic stroma, infiltration activation T cells, low mutational burden. The genetic landscape PDAC defined activating KRAS mutations (~90%) p53 alterations (~70%), but the molecular switches perturbed these aberrations remain unclear. missense mutations, unlike resulting in loss p53, are considered acquire...
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer without effective treatments. It characterized by activating KRAS mutations and p53 alterations. However, how these dysregulate cancer-cell-intrinsic gene programs to influence the immune landscape of tumor microenvironment (TME) remains poorly understood. Here, we show that
Summary Heat shock triggers an instant reprogramming of gene and enhancer transcription, but whether cells encode a memory to stress, at the level nascent has remained unknown. Here, we measured transcriptional response acute heat stress in unconditioned daughters that had been exposed single or multiple shocks. Tracking RNA Polymerase II (Pol II) genome-wide nucleotide-resolution revealed precisely remember their identity throughout restoring Pol distribution bodies enhancers upon recovery....
Heat shock instantly reprograms gene and enhancer transcription. Yet, it has remained unknown whether cells encode a memory to stress, at the level of nascent Here, we measured transcriptional response acute heat stress in unconditioned daughters that had been exposed single or multiple shocks. Tracking RNA Polymerase II (Pol II) genome-wide nucleotide-resolution revealed precisely remember their identity throughout restoring Pol distribution bodies enhancers upon recovery. However, primed...
Promoters and enhancers have been conventionally regarded as structurally functionally distinct genomic entities. Nonetheless, in mammals, they share many features, including divergent transcription common factors. Here, we examine the architecture of initiation through comprehensive mapping start sites (TSSs) human cell lines. Using a nuclear run‐on protocol called GRO‐cap, which captures TSSs for both stable unstable transcripts, conduct detailed comparisons thousands promoters enhancers....
Abstract RNA Polymerase II (Pol II) is the molecular machine that transcribes all protein-encoding mRNAs as well a spectrum of non-coding regulatory RNAs. The distribution Pol reveals not only location and levels transcription these transcribed genes, but also, distinctive patterns divergent can be used to identify active promoters enhancers regulate genes. Moreover, by monitoring changes in across genomes response either signals directed perturbations factors, distinct steps are regulated...
<h3>Background</h3> Myeloid cells, unlike other immune cells such as T or NK are known residents in the solid tumor microenvironment (TME). In absence of checkpoints and proinflammatory conditions, M1 macrophages to be capable direct phagocytosis can present tumor-associated antigens host system. However, immunosuppressive conditions within TME restrict limit anti-tumor response associated (TAMs), including their ability recruit activate against tumor. Engineered CAR-Monocytes serve a unique...
SummaryIn embryonic stem cells (ESCs), heterogeneous gene expression impacts cell-fate decision making and pluripotency. Cell-to-cell variation in is a key feature of cell systems, yet its origins remain unknown. Here we identify coherent regulatory program enhancers that are dynamically transcribed across ESCs. Variable drive developmental genes transcription factors (TFs). Systematic analysis enhancer transcription, accessibility, function demonstrates variable regulate state-specific...