A5013992863- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Renal and related cancers
- Pluripotent Stem Cells Research
- Ovarian cancer diagnosis and treatment
- Cancer Treatment and Pharmacology
- Cancer-related gene regulation
- Cancer-related molecular mechanisms research
- Breast Cancer Treatment Studies
- HER2/EGFR in Cancer Research
- TGF-β signaling in diseases
- Empathy and Medical Education
- Protein Degradation and Inhibitors
- Film in Education and Therapy
- Cancer Genomics and Diagnostics
- CRISPR and Genetic Engineering
- Chemical Reactions and Isotopes
- Advanced Breast Cancer Therapies
- Gene expression and cancer classification
- Fungal and yeast genetics research
- Genetics and Neurodevelopmental Disorders
- 3D Printing in Biomedical Research
- Respiratory and Cough-Related Research
Cedars-Sinai Medical Center
2019-2023
Dana-Farber Cancer Institute
1994-2023
Eli and Edythe Broad Foundation
2023
Broad Institute
2023
University of Pennsylvania
2023
Cancer Research Center
2023
Johns Hopkins Medicine
2023
Johns Hopkins University
2023
Massachusetts Institute of Technology
2011-2022
University of Colorado Boulder
2022
Oncogenes are activated through well-known chromosomal alterations such as gene fusion, translocation, and focal amplification. In light of recent evidence that the control key genes depends on chromosome structures called insulated neighborhoods, we investigated whether proto-oncogenes occur within these oncogene activation can via disruption neighborhood boundaries in cancer cells. We mapped neighborhoods T cell acute lymphoblastic leukemia (T-ALL) found tumor genomes contain recurrent...
Embryonic stem cells (ESCs) of mice and humans have distinct molecular biological characteristics, raising the question whether an earlier, "naive" state pluripotency may exist in humans. Here we took a systematic approach to identify small molecules that support self-renewal naive human ESCs based on maintenance endogenous OCT4 distal enhancer activity, signature ground pluripotency. Iterative chemical screening identified combination five kinase inhibitors induces maintains activity when...
A small set of core transcription factors (TFs) dominates control the gene expression program in embryonic stem cells and other well-studied cellular models. These TFs collectively regulate their own expression, thus forming an interconnected auto-regulatory loop that can be considered transcriptional regulatory circuitry (CRC) for cell type. There is limited knowledge TFs, models circuitry, most types. We recently discovered genes encoding known CRCs are driven by super-enhancers, which...
(Cell Stem Cell 15, 471–487; October 2, 2014) We have identified two errors in the data presentation version of this paper originally published online on July 24, 2014. Neither them affects results or conclusions presented any significant way. The issues are as follows: Figure 3. chemical structure shown 3C did not represent WH-4-023, but instead a closely related LCK/SRC inhibitor called WH-4-025. To correct figure we replaced with for WH-4-023 and, completeness, added citation to legend...
Abstract The functional consequences of somatic non-coding mutations in ovarian cancer (OC) are unknown. To identify regulatory elements (RE) and genes perturbed by acquired variants, here we establish epigenomic transcriptomic landscapes primary OCs using H3K27ac ChIP-seq RNA-seq, then integrate these with whole genome sequencing data from 232 OCs. We 25 frequently mutated elements, including an enhancer at 6p22.1 which associates differential expression ZSCAN16 (P = 6.6 × 10-4) ZSCAN12...
PAX8 is a master transcription factor that essential during embryogenesis and promotes neoplastic growth. It expressed by the secretory cells lining female reproductive tract, its deletion development results in atresia of tract organs. Nearly all ovarian carcinomas express PAX8, knockdown apoptosis cancer cells. To explore role these tissues, we purified protein complex from nonmalignant fallopian tube high-grade serous carcinoma cell lines. We found was member large chromatin remodeling...
The CaCTS algorithm nominates cancer cell master transcription factors and guides a model of ovarian regulatory circuitry.
We previously demonstrated that the Drosophila Krüppel protein is a transcriptional repressor with separable DNA-binding and repression activities. In this study, minimal amino (N)-terminal region of was defined by transferring regions to heterologous protein, lacI protein. Fusion predicted alpha-helical from acids 62 92 in N terminus sufficient transfer activity. This putative alpha-helix has several hydrophobic surfaces, as well glutamine-rich surface. Mutants containing multiple acid...
The function of critical developmental regulators can be subverted by cancer cells to control expression oncogenic transcriptional programs. These "master transcription factors" (MTFs) are often essential for cell survival and represent vulnerabilities that exploited therapeutically. current approaches identify candidate MTFs examine super-enhancer associated factor-encoding genes with high connectivity in network models. This relies on chromatin immunoprecipitation-sequencing (ChIP-seq)...
ABSTRACT Worldwide, the number of new ovarian cancer cases approaches 300,000 with more than 180,000 deaths every year. The low survival-rate reflects limitations current therapies and highlights importance identifying therapeutic targets. Despite significant recent efforts to identify novel vulnerabilities in cancer, none have led effective durable improvement overall survival. PAX8, a lineage-transcription factor, whose expression is major molecular feature carcinomas, represents target....
ABSTRACT The transcription factors MECOM, PAX8, SOX17 and WT1 are candidate master regulators of high-grade serous ‘ovarian’ cancer (HGSC), yet their cooperative role in the hypothesized tissue origin, fallopian tube secretory epithelium (FTSEC) is unknown. We generated 26 epigenome (CUT&TAG, CUT&RUN, ATAC-seq HiC) data sets 24 profiles RNA-seq factor knock-down followed by RNA sequencing FTSEC HGSC models to define binding sites gene regulated these cis trans . This revealed that...
ABSTRACT Transcriptional regulation is highly disease and cell-type specific. We performed H3K27ac chromatin immunoprecipitation transcriptomic sequencing in primary tumors for the four different subtypes of invasive epithelial ovarian cancer (OC). Histotype-specific regulatory elements (REs) were enriched enhancers (P<0.001). In silico prediction putative target genes histotype-specific REs identified ( WFDC2 , P=5.5×10 -5 ) pathways (PI3K-Akt signaling, P<0.002) known to be involved...
9580 Background: Trastuzumab (Herceptin®, H) is a humanized monoclonal antibody which showed significant survival benefit in randomized trial comparing chemotherapy plus H vs. alone patients (pts) with MBC whose HER2 status was determined by immunohistochemistry (IHC). Retrospective analysis of this that the limited to pts who tested HER2+ fluorescence situ hybridization (FISH). We report concordance results between local lab (LL) and central (CL) testing from phase IV study taxane MBC....
The transcription factors MECOM, PAX8, SOX17 and WT1 are candidate master regulators of high-grade serous ‘ovarian’ cancer (HGSC), yet their cooperative role in the hypothesized tissue origin, fallopian tube secretory epithelium (FTSEC) is unknown. We generated 26 epigenome (CUT&TAG, CUT&RUN, ATAC-seq HiC) data sets 24 profiles RNA-seq factor knock-down followed by RNA sequencing FTSEC HGSC models to define binding sites gene regulated these cis trans . This revealed that...