A5090349098- Estrogen and related hormone effects
- Computational Drug Discovery Methods
- Bioinformatics and Genomic Networks
- Gene Regulatory Network Analysis
- Cancer Genomics and Diagnostics
- Genomics and Chromatin Dynamics
- Renal and related cancers
- Single-cell and spatial transcriptomics
- Steroid Chemistry and Biochemistry
- Particle accelerators and beam dynamics
- Gene expression and cancer classification
- 14-3-3 protein interactions
- Ubiquitin and proteasome pathways
- Protein Tyrosine Phosphatases
- Microtubule and mitosis dynamics
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- interferon and immune responses
- CRISPR and Genetic Engineering
- Cancer Mechanisms and Therapy
- Chromatin Remodeling and Cancer
- Renal cell carcinoma treatment
Novartis Institutes for BioMedical Research
2019-2024
Novartis (Switzerland)
2019-2024
Abstract Transcription factor networks shape the gene expression programs responsible for normal cell identity and pathogenic state. Using Core Regulatory Circuitry analysis (CRC), we identify PAX8 as a candidate oncogene in Renal Cell Carcinoma (RCC) cells. Validation of large-scale functional genomic screens confirms that silencing leads to decreased proliferation RCC lines. Epigenomic analyses PAX8-dependent cistrome demonstrate largely occupies active enhancer elements controlling genes...
Abstract The transcription factor PAX8 is critical for the development of thyroid and urogenital system. Comprehensive genomic screens furthermore indicate an additional oncogenic role in renal ovarian cancers. While a plethora PAX8-regulated genes different contexts have been proposed, we still lack mechanistic understanding how engages molecular complexes to drive disease-relevant transcriptional programs. Here show that protein isoforms originating from MECOM locus form complex with PAX8....
Abstract RAS–MAPK signalling is fundamental for cell proliferation and altered in most human cancers 1–3 . However, our mechanistic understanding of how RAS signals through RAF still incomplete. Although studies revealed snapshots autoinhibited active RAF–MEK1–14-3-3 complexes 4 , the intermediate steps that lead to activation remain unclear. The MRAS–SHOC2–PP1C holophosphatase dephosphorylates at serine 259, resulting partial displacement 14-3-3 RAF–RAS association 3,5,6 MRAS, SHOC2 PP1C...
Abstract ARID1B is a SWI/SNF subunit frequently mutated in human Coffin–Siris syndrome (CSS) and it necessary for proliferation of ARID1A mutant cancers. While most CSS aberrations introduce frameshifts or stop codons, the functional consequence missense mutations found unclear. We here perform saturated mutagenesis screens on demonstrate that protein destabilization main mechanism associated with pathogenic patients Syndrome.
Combination of functional epigenomics and single-cell CRISPR screens reveals that ER exerts its oncogenic role via downstream TFs.
Abstract Only a handful of somatic alterations have been linked to endocrine therapy resistance in hormone-dependent breast cancer, potentially explaining ∼40% relapses. If other mechanisms underlie the evolution cancer under adjuvant is currently unknown. In this work, we employ functional genomics dissect contribution cis-regulatory elements (CRE) by focusing on 12 megabases noncoding DNA, including clonal enhancers, gene promoters, and boundaries topologically associating domains....
<p>Supplementary Figure 8. SIDP identifies regulatory regions with context-dependent activity in MCF7 cells.</p>
<p>Supplementary Figure 9. SIDP identifies regulatory regions with context-dependent activity in MCF7 cells.</p>
<p>Supplementary Figure 3. Estrogen deprivation in MCF7 cells introduce stochastic selective pressure long-term CRISPRi screens.</p>
<p>Supplementary Figure 6. SIDP results are consistent across ER+ BC cell lines.</p>
<p>Supplementary Figure 17. Activation of TLR5 via paracrine signaling.</p>
<p>Supplementary Figure 16. Genes involved in TLR signaling are upregulated MCF7 during therapy induced dormancy.</p>
<p>Supplementary Figure 7. SIDP identifies regulatory regions with context-dependent activity in MCF7 cells.</p>
<p>Supplementary Figure 8. SIDP identifies regulatory regions with context-dependent activity in MCF7 cells.</p>