Thomas F. Westbrook

ORCID: 0009-0006-9711-5710
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About
Contact & Profiles
Research Areas
  • RNA modifications and cancer
  • Glioma Diagnosis and Treatment
  • Cancer-related molecular mechanisms research
  • Epigenetics and DNA Methylation
  • PARP inhibition in cancer therapy
  • DNA Repair Mechanisms
  • Ferroptosis and cancer prognosis
  • Circular RNAs in diseases
  • Ubiquitin and proteasome pathways
  • MicroRNA in disease regulation
  • Cancer-related Molecular Pathways
  • RNA Research and Splicing
  • Cancer-related gene regulation
  • Microtubule and mitosis dynamics
  • Cancer Cells and Metastasis
  • Protein Degradation and Inhibitors
  • Cancer, Hypoxia, and Metabolism
  • Protein Tyrosine Phosphatases
  • CRISPR and Genetic Engineering
  • Galectins and Cancer Biology
  • PI3K/AKT/mTOR signaling in cancer
  • interferon and immune responses
  • Neuroblastoma Research and Treatments
  • Cancer Genomics and Diagnostics
  • GDF15 and Related Biomarkers

Baylor College of Medicine
2016-2025

Children's Cancer Center
2011-2021

Dan L Duncan Comprehensive Cancer Center
2012-2021

University of North Carolina at Chapel Hill
2012

Pediatrics and Genetics
2011

Howard Hughes Medical Institute
2005-2008

Brigham and Women's Hospital
2008

Massachusetts General Hospital
2008

Cold Spring Harbor Laboratory
2008

Harvard University
2004-2008

The discovery of RNAi has revolutionized loss-of-function genetic studies in mammalian systems. However, significant challenges still remain to fully exploit for genetics. For instance, screens and vivo could be broadly improved by methods that allow inducible uniform gene expression control. To achieve this, we built the lentiviral pINDUCER series vehicles vivo. Using a multicistronic design, enable tracking viral transduction shRNA or cDNA induction broad spectrum cell types They this...

10.1073/pnas.1019736108 article EN Proceedings of the National Academy of Sciences 2011-02-09

Myc is an oncogenic transcription factor frequently dysregulated in human cancer. To identify pathways supporting the program, we used a genome-wide RNA interference screen to search for Myc-synthetic lethal genes and uncovered role SUMO-activating enzyme (SAE1/2). Loss of SAE1/2 enzymatic activity drives synthetic lethality with Myc. Inactivation SAE2 leads mitotic catastrophe cell death upon hyperactivation. Mechanistically, inhibition switches transcriptional subprogram from activated...

10.1126/science.1212728 article EN Science 2011-12-09

The integration of mass spectrometry-based proteomics with next-generation DNA and RNA sequencing profiles tumors more comprehensively. Here this "proteogenomics" approach was applied to 122 treatment-naive primary breast cancers accrued preserve post-translational modifications, including protein phosphorylation acetylation. Proteogenomics challenged standard cancer diagnoses, provided detailed analysis the ERBB2 amplicon, defined tumor subsets that could benefit from immune checkpoint...

10.1016/j.cell.2020.10.036 article EN cc-by-nc-nd Cell 2020-11-01

Metabolic profiling of cancer cells has recently been established as a promising tool for the development therapies and identification biomarkers. Here we characterized metabolomic profile human breast tumors uncovered intrinsic metabolite signatures in these using an untargeted discovery approach validation key metabolites. The oncometabolite 2-hydroxyglutarate (2HG) accumulated at high levels subset cell lines. We discovered association between increased 2HG MYC pathway activation cancer,...

10.1172/jci71180 article EN Journal of Clinical Investigation 2013-12-08

Retroviral short hairpin RNA (shRNA)-mediated genetic screens in mammalian cells are powerful tools for discovering loss-of-function phenotypes. We describe a highly parallel multiplex methodology screening large pools of shRNAs using half-hairpin barcodes microarray deconvolution. carried out dropout that affect cell proliferation and viability cancer normal cells. identified many to be antiproliferative target core cellular processes, such as the cycle protein translation, all examined....

10.1126/science.1149200 article EN Science 2008-02-01

RNA-binding proteins (RBPs) are critical regulators of post-transcriptional gene expression, and aberrant RBP-RNA interactions can promote cancer progression. Here, we interrogate the function RBPs in using pooled CRISPR-Cas9 screening identify 57 RBP candidates with distinct roles supporting MYC-driven oncogenic pathways. We find that disrupting YTHDF2-dependent mRNA degradation triggers apoptosis triple-negative breast (TNBC) cells tumors. eCLIP m6A sequencing reveal YTHDF2 interacts mRNAs...

10.1016/j.molcel.2021.06.014 article EN cc-by Molecular Cell 2021-07-02

Localization to sites of DNA damage is a hallmark response (DDR) proteins. To identify DDR factors, we screened epitope-tagged proteins for localization chromatin damaged by UV laser microirradiation and found >120 that localize chromatin. These include the BAF tumor suppressor complex amyotrophic lateral sclerosis (ALS) candidate protein TAF15. TAF15 contains multiple domains bind in poly-(ADP-ribose) polymerase (PARP)-dependent manner, suggesting possible role as glue tethers PAR chains...

10.1016/j.celrep.2015.04.053 article EN cc-by-nc-nd Cell Reports 2015-05-21
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