A5038350547- Bone Tumor Diagnosis and Treatments
- Sarcoma Diagnosis and Treatment
- Lung Cancer Treatments and Mutations
- interferon and immune responses
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- MicroRNA in disease regulation
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Lung Cancer Research Studies
- Cell Adhesion Molecules Research
- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
- Genomics and Chromatin Dynamics
- Genetics and Neurodevelopmental Disorders
- Fibroblast Growth Factor Research
- Peptidase Inhibition and Analysis
- Neuroendocrine Tumor Research Advances
- Ear and Head Tumors
- CRISPR and Genetic Engineering
- Cancer therapeutics and mechanisms
- RNA Research and Splicing
- Quinazolinone synthesis and applications
Broad Institute
2010-2023
Dana-Farber Cancer Institute
2011-2015
Harvard University
2010-2015
Massachusetts Institute of Technology
2010-2014
More complete knowledge of the molecular mechanisms underlying cancer will improve prevention, diagnosis and treatment. Efforts such as The Cancer Genome Atlas are systematically characterizing structural basis cancer, by identifying genomic mutations associated with each type. A powerful complementary approach is to characterize functional genes essential for growth related phenotypes in different cells. Such information would be particularly valuable potential drug targets. Here, we report...
Background Squamous cell lung carcinomas account for approximately 25% of new carcinoma cases and 40,000 deaths per year in the United States. Although there are multiple genomically targeted therapies adenocarcinoma, none has yet been reported squamous carcinoma. Methodology/Principal Findings Using SNP array analysis, we found that a region chromosome segment 8p11-12 containing three genes–WHSC1L1, LETM2, FGFR1–is amplified 3% adenocarcinomas 21% carcinomas. Furthermore, demonstrated...
Although recurrent somatic mutations in the splicing factor U2AF1 (also known as U2AF35) have been identified multiple cancer types, effects of these on transcriptome yet to be fully elucidated. Here, we alterations associated with across distinct cancers using DNA and RNA sequencing data from The Cancer Genome Atlas (TCGA). Using RNA-Seq 182 lung adenocarcinomas 167 acute myeloid leukemias (AML), which is somatically mutated 3-4% cases, 131 369 alterations, respectively, that were...
Abstract Identifying the spectrum of genes required for cancer cell survival can reveal essential circuitry and therapeutic targets, but such a map remains incomplete many types. We apply genome-scale CRISPR-Cas9 loss-of-function screens to landscape selectively in chordoma, bone with few validated targets. This approach confirms known chordoma dependency, TBXT ( T ; brachyury), identifies range additional dependencies, including PTPN11, ADAR, PRKRA, LUC7L2, SRRM2 , SLC2A1, SLC7A5, FANCM...
High-content screening for small-molecule inducers of insulin expression identified the compound BRD7389, which caused α-cells to adopt several morphological and gene features a β-cell state. Assay-performance profile analysis suggests kinase inhibition as mechanism action, we show that biochemical cellular RSK family by BRD7389 is likely related its ability induce β-cell-like also increases endocrine cell content function donor human pancreatic islets in culture.
Significance Non-small cell lung cancers (NSCLCs) harboring mutations in the epidermal growth factor receptor ( EGFR ) gene are often singularly reliant on activity for tumor survival, but genetic basis this dependence is not fully understood. In study, we have performed a screen to identify spectrum of kinase genes whose overexpression can overcome NSCLC cells’ reliance EGFR. Using both unbiased and targeted approaches, demonstrate that these commonly bypass through reactivation downstream...
Chordomas are rare spinal tumors addicted to expression of the developmental transcription factor brachyury. In chordomas, brachyury is super-enhancer associated and preferentially downregulated by pharmacologic transcriptional CDK inhibition, leading cell death. To understand underlying basis this sensitivity, we dissect regulatory network compare consequences degradation with inhibition. Brachyury defines chordoma landscape autoregulates through binding its super-enhancer, locus forms a...
Abstract Dysregulated gene programs are a hallmark of cancer, and oncogenic transcription factors (TFs) have emerged as key players that contribute to this cell state. Chordoma is rare cancer derived from deregulation the TF brachyury (encoded by T gene). While normally turned off in development minimally expressed healthy tissues, it remains highly required chordoma. TFs like been challenging drug directly, chordoma represents an ideal system for studying both biology behind transcriptional...
ABSTRACT Identifying the spectrum of genes required for cancer cell survival can reveal essential circuitry and therapeutic targets, but such a map remains incomplete many types. We applied genome-scale CRISPR-Cas9 loss-of-function screens to landscape selectively in chordoma, bone with few validated targets. This approach confirmed known chordoma dependency, TBXT ( T ; brachyury), identified range additional dependencies, including PTPN11, ADAR, PRKRA, LUC7L2, SRRM2, SLC2A1, SLC7A5, FANCM ,...
Abstract Chordomas are rare spinal tumors addicted to expression of the developmental transcription factor brachyury. In chordomas, brachyury is super-enhancer associated and preferentially downregulated by pharmacologic transcriptional CDK inhibition leading cell death. To understand underlying basis this sensitivity, we dissect regulatory network compare consequences degradation with inhibition. Brachyury defines chordoma landscape, autoregulates through binding its super-enhancer, locus...