A5047856714- Ubiquitin and proteasome pathways
- Endoplasmic Reticulum Stress and Disease
- Ferroptosis and cancer prognosis
- CRISPR and Genetic Engineering
- Hippo pathway signaling and YAP/TAZ
- Microtubule and mitosis dynamics
- Brain Metastases and Treatment
- Cancer-related Molecular Pathways
- DNA Repair Mechanisms
- Cancer-related gene regulation
- Genetic factors in colorectal cancer
- Genetics, Bioinformatics, and Biomedical Research
- Eosinophilic Esophagitis
- Autophagy in Disease and Therapy
- Virus-based gene therapy research
- RNA modifications and cancer
- Lung Cancer Treatments and Mutations
- Epigenetics and DNA Methylation
- PARP inhibition in cancer therapy
- BRCA gene mutations in cancer
- Lung Cancer Research Studies
- IL-33, ST2, and ILC Pathways
- Nuclear Structure and Function
Cornell University
2025
Memorial Sloan Kettering Cancer Center
2025
Broad Institute
2018-2022
Harvard Stem Cell Institute
2019
Harvard University
2019
Eli and Edythe Broad Foundation
2018
Abstract Systematic identification of signaling pathways required for the fitness cancer cells will facilitate development new therapies. We used gene essentiality measurements in 1,086 cell lines to identify selective coessentiality modules and found that a ubiquitin ligase complex composed UBA6, BIRC6, KCMF1, UBR4 is survival subset epithelial tumors exhibit high degree aneuploidy. Suppressing BIRC6 are dependent on this led substantial reduction vitro potent tumor regression vivo....
Microsatellite instability (MSI), a class of genetic hypermutability that arises from impaired DNA mismatch repair (MMR), contributes to the development many malignancies including colon, endometrial, gastric, and ovarian cancers. While immune checkpoint blockade (ICB) has been an effective therapy for patients with MSI cancers, numerous do not respond ICB or use these agents are limited by their toxicity. Hence, there is still pressing need develop further therapies against One approach...
Synthetic lethality, an interaction whereby the co-occurrence of two or more genetic events lead to cell death but one event alone does not, can be exploited develop novel cancer therapeutics. DNA repair processes represent attractive synthetic lethal targets since many cancers exhibit impaired pathway, which these cells become dependent on specific proteins. The success poly (ADP-ribose) polymerase 1 (PARP-1) inhibitors in homologous recombination-deficient highlights potential this...
<div>Abstract<p>Systematic identification of signaling pathways required for the fitness cancer cells will facilitate development new therapies. We used gene essentiality measurements in 1,086 cell lines to identify selective coessentiality modules and found that a ubiquitin ligase complex composed <i>UBA6</i>, <i>BIRC6</i>, <i>KCMF1</i>, <i>UBR4</i> is survival subset epithelial tumors exhibit high degree aneuploidy. Suppressing...
<p>Supplementary Figure S1 shows the strategy and result of co-essentiality module identificationfrom DepMap CRISPR screen dataset further characterization BIRC6 module. Supplementary S2 viability effect depletion in BIRC6-dependent -nondependent cancer cells lines as well asin nontransformed cells. S3 vitro confirmations inducible (by RNAi CRISPR) systems on metastasis xenograft models. S4 detailed results for allele competition assay to evaluate role BIR UBC domains evidence physical...
<div>Abstract<p>Systematic identification of signaling pathways required for the fitness cancer cells will facilitate development new therapies. We used gene essentiality measurements in 1,086 cell lines to identify selective coessentiality modules and found that a ubiquitin ligase complex composed <i>UBA6</i>, <i>BIRC6</i>, <i>KCMF1</i>, <i>UBR4</i> is survival subset epithelial tumors exhibit high degree aneuploidy. Suppressing...
<p>Supplementary Figure S1 shows the strategy and result of co-essentiality module identificationfrom DepMap CRISPR screen dataset further characterization BIRC6 module. Supplementary S2 viability effect depletion in BIRC6-dependent -nondependent cancer cells lines as well asin nontransformed cells. S3 vitro confirmations inducible (by RNAi CRISPR) systems on metastasis xenograft models. S4 detailed results for allele competition assay to evaluate role BIR UBC domains evidence physical...
Abstract BACKGROUND The prognosis for patients with brain metastasis (BM) is devastating, while the underlying biology of BM development remains poorly understood. Identification genomic biomarkers can offer promising opportunities prediction and guidance in personalized treatment. In this study we evaluate alterations present a large cohort resected BM. METHODS Upon retrospective review, identified 868 diagnosis solid primary cancers who had undergone standard care craniotomy at Memorial...
Abstract Microsatellite instability (MSI), a class of genetic hypermutability that arises from impaired DNA mismatch repair (MMR), contributes to the development many malignancies including colon, endometrial, gastric, and ovarian cancers. While immune checkpoint blockade (ICB) has been an effective therapy for patients with MSI cancers, numerous do not respond ICB or use these agents are limited by their toxicity. Hence, there is still pressing need develop further therapies against One...
Abstract Despite its increasing success and revolutionary impact on clinical oncology, Precision Cancer Medicine still has major roadblocks before it becomes applicable to a large proportion of patients. One such roadblock is the limited number therapeutic targets available. Indeed, for vast majority cancer patients, we either do not know what their specific vulnerabilities are or have strategies precisely target vulnerabilities. In Dependency Map Project (DepMap) at Broad Institute, aim...
Abstract Targeting of mutated oncogenes has led to the identification new targeted therapies. However, druggable do not occur in most cancers. Systematic signaling pathways required for fitness cancer cells will facilitate development We used gene essentiality measurements 793 cell lines identify selective co-essentiality modules and found that a ubiquitination ligase complex composed UBA6, BIRC6, KCMF1 UBR4, which encode an E1, E2 two heterodimeric E3 subunits, respectively, is survival...
Abstract Targeting of mutated oncogenes has led to the identification new targeted therapies. However, druggable do not occur in most cancers. Systematic signaling pathways required for fitness cancer cells will facilitate development We used gene essentiality measurements 793 cell lines identify selective co-essentiality modules and found that a ubiquitination ligase complex composed UBA6, BIRC6, KCMF1 UBR4, which encode an E1, E2 two heterodimeric E3 subunits, respectively, is survival...
Abstract Systematic identification of signaling pathways required for the viability cancer cells will facilitate development novel therapies. We used gene essentiality measurements in 726 cell lines to identify selective co-essentiality modules and found a functional ubiquitination cascade containing UBA6, BIRC6, KCMF1 UBR4, which encode an E1, E2, two heterodimeric E3 subunits, respectively, as vulnerability subset epithelial tumors. Suppressing BIRC6 that are dependent on this led strong...