Thomas F. Westbrook
A5041015197- 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...
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...
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...
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,...
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....
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...
Precision medicine relies on identifying reliable biomarkers for gene dependencies to tailor individualized therapeutic strategies. The advent of high-throughput technologies presents unprecedented opportunities explore molecular disease mechanisms but also challenges due high dimensionality and collinearity among features. Traditional statistical methods often fall short in this context, necessitating novel computational approaches that harness the full potential big data bioinformatics....
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...