Steven M. Corsello
A5082563631- Cancer Genomics and Diagnostics
- Colorectal Cancer Treatments and Studies
- HER2/EGFR in Cancer Research
- Genetic factors in colorectal cancer
- Monoclonal and Polyclonal Antibodies Research
- Computational Drug Discovery Methods
- Protein Degradation and Inhibitors
- Cancer Immunotherapy and Biomarkers
- Gastric Cancer Management and Outcomes
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Bioinformatics and Genomic Networks
- RNA modifications and cancer
- Genomics and Rare Diseases
- Cell Image Analysis Techniques
- Molecular Biology Techniques and Applications
- Trace Elements in Health
- Lung Cancer Treatments and Mutations
- Renal and related cancers
- Acute Myeloid Leukemia Research
- Histone Deacetylase Inhibitors Research
- Cancer Cells and Metastasis
- Advanced Fluorescence Microscopy Techniques
- Ferroptosis and cancer prognosis
Stanford University
2023-2025
Stanford Medicine
2024-2025
Cancer Prevention Institute of California
2024
Stanford Cancer Institute
2024
Harvard University
2005-2023
Dana-Farber Cancer Institute
2009-2023
Broad Institute
2005-2023
Harvard University Press
2007
Howard Hughes Medical Institute
2005
Massachusetts Institute of Technology
2005
Copper is an essential cofactor for all organisms, and yet it becomes toxic if concentrations exceed a threshold maintained by evolutionarily conserved homeostatic mechanisms. How excess copper induces cell death, however, unknown. Here, we show in human cells that copper-dependent, regulated death distinct from known mechanisms dependent on mitochondrial respiration. We copper-dependent occurs means of direct binding to lipoylated components the tricarboxylic acid (TCA) cycle. This results...
Cancer genome characterization efforts now provide an initial view of the somatic alterations in primary tumors. However, most point mutations occur at low frequency, and function these alleles remains undefined. We have developed a scalable systematic approach to interrogate cancer-associated gene variants. subjected 474 mutant curated from 5,338 tumors pooled vivo tumor formation assays expression profiling. identified 12 transforming alleles, including two genes (PIK3CB, POT1) that not...
Abstract The RNF43 _p.G659fs mutation occurs frequently in colorectal cancer, but its function remains poorly understood and there are no specific therapies directed against this alteration. In study, we find that promotes cell growth independent of Wnt signaling. We perform a drug repurposing library screen discover cells with _p.G659 mutations selectively killed by inhibition PI3K PI3K/mTOR inhibitors yield promising antitumor activity 659mut isogenic lines xenograft models, as well...
SUMMARY We previously piloted the concept of a Connectivity Map (CMap), whereby genes, drugs and disease states are connected by virtue common gene-expression signatures. Here, we report more than 1,000-fold scale-up CMap as part NIH LINCS Consortium, made possible new, low-cost, high throughput reduced representation expression profiling method that term L1000. show L1000 is highly reproducible, comparable to RNA sequencing, suitable for computational inference levels 81% non-measured...
Immunotherapy with checkpoint inhibitors, such as the programmed death-1 (PD-1) antibodies pembrolizumab and nivolumab, are effective in a variety of tumors, yet not all patients respond. Tumor microsatellite instability-high (MSI-H) has emerged biomarker response to blockade, leading tissue agnostic approval MSI-H cancers. Here we describe patient colorectal cancer that was treated this immune inhibitor exhibited progression disease. We examined intrinsic resistance through genomic,...
Identifying the chemical regulators of biological pathways is a time-consuming bottleneck in developing therapeutics and research compounds. Typically, thousands to millions candidate small molecules are tested target-based biochemical screens or phenotypic cell-based screens, both expensive experiments customized each disease. Here, our uncustomized, virtual, profile-based screening approach instead identifies compounds that match based on information public cell image data, created using...
Transcriptional enhanced associate domain (TEAD) proteins together with their transcriptional coactivator yes-associated protein (YAP) and the PDZ-binding motif (TAZ) are important transcription factors cofactors that regulate gene expression in Hippo pathway. In mammals, TEAD families have four homologues: TEAD1 (TEF-1), TEAD2 (TEF-4), TEAD3 (TEF-5), TEAD4 (TEF-3). Aberrant hyperactivation of TEAD/YAP signaling been implicated a variety malignancies. Recently, TEADs were recognized as being...
Implementing cancer precision medicine in the clinic requires assessing therapeutic relevance of genomic alterations. A main challenge is systematic interpretation whole-exome sequencing (WES) data for clinical care.One hundred sixty-five adults with metastatic colorectal and lung adenocarcinomas were prospectively enrolled CanSeq study. WES was performed on DNA extracted from formalin-fixed paraffin-embedded tumor biopsy samples matched blood samples. Somatic germ-line alterations ranked...
Molecular glue degraders (MGDs) are small molecules that facilitate proximity between a target protein and an E3 ubiquitin ligase, thereby inducing degradation. Glutarimide-containing compounds MGDs bind cereblon (CRBN) recruit neosubstrates. Through explorative synthesis of glutarimide-based library, we discovered series induce casein kinase 1 alpha (CK1α) By scaffold hopping rational modification the chemical scaffold, identified imidazo[1,2-a]pyrimidine compound induces potent selective...
ABSTRACT Anti-cancer uses of non-oncology drugs have been found on occasion, but such discoveries serendipitous and rare. We sought to create a public resource containing the growth inhibitory activity 4,518 tested across 578 human cancer cell lines. To accomplish this, we used PRISM, which involves drug treatment molecularly barcoded lines in pools. Relative barcode abundance following thus reflects line viability. that an unexpectedly large number selectively inhibited subsets Moreover,...
Abstract Purpose: ERBB2-amplified colorectal cancer is a distinct molecular subtype with expanding treatments. Implications of concurrent oncogenic RAS/RAF alterations are not known. Experimental Design: Dana-Farber and Foundation Medicine Inc. Colorectal cohorts genomic profiling were used to identify cases [Dana-Farber, n = 47/2,729 (1.7%); FMI, 1857/49,839 (3.7%)]. Outcomes patients receiving HER2-directed therapies reported (Dana-Farber, 9; Flatiron Health-Foundation clinicogenomic...
Over the past three decades, high-throughput phenotypic cancer cell line screens have revealed unanticipated small-molecule activities and illuminated connections between tumor genotypes anticancer efficacy. Founded in 1984, National Cancer Institute's "NCI60" screen laid conceptual groundwork for contemporary landscape of drug discovery. NCI60 first operated as a primary bioactivity screen, but molecular characterization panel development sensitivity pattern recognition algorithm (called...
Chemical probes are essential tools for understanding biological systems and credentialing potential biomedical targets. Programmed cell death 2 (PDCD2) is a member of the B-cell lymphoma (Bcl-2) family proteins, which critical regulators apoptosis. Here we report discovery characterization 10 e, first-in-class small molecule degrader PDCD2. We discovered this PDCD2 by serendipity using chemical proteomics approach, in contrast to conventional approach making bivalent degraders starting from...
Abstract Identifying chemical regulators of biological pathways is a time-consuming bottleneck in developing therapeutics and research compounds. Typically, thousands to millions candidate small molecules are tested target-based biochemical screens or phenotypic cell-based screens, both expensive experiments customized each disease. Here, our uncustomized, virtual profile-based screening approach instead identifies compounds that match based on information public cell image data, created...
<p>Supplementary Figure 6. Generation of HER2 overexpressing CRC cell lines with endogenous KRAS mutations.</p>
<div>AbstractPurpose:<p><i>ERBB2</i>-amplified colorectal cancer is a distinct molecular subtype with expanding treatments. Implications of concurrent oncogenic <i>RAS/RAF</i> alterations are not known.</p>Experimental Design:<p>Dana-Farber and Foundation Medicine Inc. Colorectal cohorts genomic profiling were used to identify <i>ERBB2</i>-amplified cases [Dana-Farber, <i>n</i> = 47/2,729 (1.7%); FMI, 1857/49,839...