A5074311334- Bacterial Genetics and Biotechnology
- Adipose Tissue and Metabolism
- RNA and protein synthesis mechanisms
- Antibiotic Resistance in Bacteria
- Tuberculosis Research and Epidemiology
- Escherichia coli research studies
- Mycobacterium research and diagnosis
- Cancer Immunotherapy and Biomarkers
- Adipokines, Inflammation, and Metabolic Diseases
- RNA Research and Splicing
- Immunotherapy and Immune Responses
- Photosynthetic Processes and Mechanisms
- Circadian rhythm and melatonin
- Light effects on plants
- Peroxisome Proliferator-Activated Receptors
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Muscle Physiology and Disorders
- Exercise and Physiological Responses
- Hormonal Regulation and Hypertension
- Cholesterol and Lipid Metabolism
- Ion Transport and Channel Regulation
- Ferroptosis and cancer prognosis
- Mitochondrial Function and Pathology
- Thyroid Disorders and Treatments
Bristol-Myers Squibb (United States)
2022-2025
Beth Israel Deaconess Medical Center
2016-2021
Harvard University
2017-2021
Broad Institute
2017-2020
Genocea (United States)
2019
Boston University
2012-2017
Lomonosov Moscow State University
2006
The chronic inflammatory state that accompanies obesity is a major contributor to insulin resistance and other dysfunctional adaptations in adipose tissue. Cellular secreted factors promote the milieu of obesity, but transcriptional pathways drive these processes are not well described. Although canonical transcription factor NF-κB considered be driver adipocyte inflammation, members interferon regulatory (IRF) family may also play role this process. Here, we determined IRF3 expression...
Enteric Escherichia coli survives the highly acidic environment of stomach through multiple acid resistance (AR) mechanisms. The most effective system, AR2, decarboxylates externally-derived glutamate to remove cytoplasmic protons and excrete GABA. first described AR1, does not require an external amino acid. Its mechanism has been determined. regulation AR systems their coordination with broader cellular metabolism fully explored.We utilized a combination ChIP-Seq gene expression analysis...
Epigenomic mechanisms direct distinct gene expression programs for different cell types. Various in vivo tissues have been subjected to epigenomic analysis; however, these studies limited by cellular heterogeneity, resulting composite and profiles. Here, we introduce "NuTRAP," a transgenic mouse that allows simultaneous isolation of cell-type-specific translating mRNA chromatin from complex tissues. Using NuTRAP, successfully characterize states various adipocyte populations vivo, revealing...
Insulin resistance results from an intricate interaction between genetic make-up and environment, thus may be orchestrated by epigenetic mechanisms like DNA methylation. Here, we demonstrate that methyltransferase 3a (Dnmt3a) is both necessary sufficient to mediate insulin in cultured mouse human adipocytes. Furthermore, adipose-specific Dnmt3a knock-out mice are protected diet-induced glucose intolerance without accompanying changes adiposity. Unbiased gene profiling studies revealed Fgf21...
The filamentous fungus Neurospora crassa responds to light in complex ways. To thoroughly study the transcriptional response of this organism light, RNA-seq was used analyze capped and polyadenylated mRNA prepared from mycelium grown for 24 hr dark then exposed 0 (control) 15, 60, 120, 240 min. More than three-quarters all defined protein coding genes (79%) were expressed these cells. increased sensitivity compared with previous microarray studies revealed that RNA levels 31% affected...
Obesity due to overnutrition causes adipose tissue dysfunction, which is a critical pathological step on the road type 2 diabetes (T2D) and other metabolic disorders. In this study, we conducted an unbiased investigation into fundamental molecular mechanisms by adipocytes transition unhealthy state during obesity.We used nuclear tagging translating ribosome affinity purification (NuTRAP) reporter mice crossed with Adipoq-Cre determine adipocyte-specific 1) transcriptional profiles (RNA-seq),...
Tumor heterogeneity is a major challenge for oncology drug discovery and development. Understanding of the spatial tumor landscape key to identifying new targets impactful model systems. Here, we test utility transcriptomics (ST) by profiling 40 tissue sections 80,024 capture spots across diverse set types, sample formats, RNA chemistries. We verify accuracy fidelity ST leveraging matched pathology analysis, which provides ground truth section composition. then use data demonstrate depth...
Expression of SigH, one 12 Mycobacterium tuberculosis alternative sigma factors, is induced by heat, oxidative and nitric oxide stresses. SigH activation has been shown to increase expression several genes, including genes involved in maintaining redox equilibrium protein degradation. However, few these are known be directly regulated SigH. The goal this project comprehensively define the operons that controlled order gain insight into role regulating M. physiology. We used ChIP-Seq identify...
Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape across multiple cancer types achieving durable responses for a significant number of patients. Despite their success, many patients still fail to respond ICIs or develop resistance soon after treatment. We sought identify early features associated with ICI outcome. leveraged MC38 syngeneic tumor model because it has variable response therapy driven by intrinsic heterogeneity. was assessed based on level immune cell...
Bacterial pathogens adapt to changing environments within their hosts, and the signaling molecule adenosine 3′, 5′-cyclic monophosphate (cAMP) facilitates this process. In study, we characterized in vivo DNA binding gene regulation by cAMP-responsive protein CRP M. bovis BCG as a model for tuberculosis (TB)-complex bacteria. Chromatin immunoprecipitation followed deep-sequencing (ChIP-seq) showed that associates with ∼900 regions, most of which occur genes. The highly enriched region was...
Mycobacterium tuberculosis (Mtb) Cmr (Rv1675c) is a CRP/FNR family transcription factor known to be responsive cAMP levels and during macrophage infections. However, Cmr's DNA binding properties, cellular targets overall role in (TB) complex bacteria have not been characterized. In this study, we used experimental computational approaches characterize properties identify putative regulon. binds 16-bp palindromic site that includes four highly conserved nucleotides are required for binding. A...
The transcription factor ChREBP mediates lipid accumulation in the liver response to thyroid hormone.
Abstract Light and the circadian clock have a profound effect on biology of organisms through regulation large sets genes. Toward understanding how light regulate gene expression, we used genome-wide approaches to identify direct indirect targets light-responsive clock-controlled transcription factor ADV-1 in Neurospora crassa. A proportion were found be light- and/or clock-controlled, enriched for genes involved development, metabolism, cell growth, fusion. We show that is necessary...
Significance Thyroid hormone receptors (TRs) mediate the genomic actions of thyroid hormones. In absence T3 (3,3′,5-triiodothyronine), TR recruits a multiprotein repressor complex that decreases histone acetylation in vicinity target genes. Nuclear receptor corepressor 1 (NCoR1) is hypothesized to be main interacts with TR. Here we report deletion NCoR1 does not prevent all gene repression and deacetylation across variety mouse models, whereas only lack was able overturn effects...
The comprehension of protein and DNA binding in vivo is essential to understand gene regulation. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) provides a global map the regulatory network. Most ChIP-seq analysis tools focus on identifying regions from coverage enrichment. However, less work has been performed infer physical details inside enriched regions. This research extends previous blind-deconvolution approach develop post-peak-calling algorithm that improves site...
Abstract Background: Transcriptomic profiles of primary high grade prostate cancer (hgPCa) have been extensively studied and prognostic gene expression signatures to classify patients for risk identified. However, such studies employed bulk genomic techniques that blur the contributions different cell types. Indeed, tumor microenvironment (TME) cells can significantly contribute these transcriptomic thereby confounding lineage potential therapeutic targets. These challenges underscore...
Abstract Pancreatic Ductal Adenocarcinoma (PDAC) is heterogeneous with low tumor purity, prominent microenvironment and complex architecture, which preclude identification of shared intrinsic biology within across patients. We overcame these challenges by applying complementary spatial omics approaches – providing necessary resolution context to primary untreated PDAC tumors from 39 patients capturing 341,949 low-bulk 531,718 single-cell transcriptomes. Of these, 59,403 profiles 205,665...