A5022005632- CRISPR and Genetic Engineering
- Immunotherapy and Immune Responses
- Renal and related cancers
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Ubiquitin and proteasome pathways
- RNA Interference and Gene Delivery
- Diet and metabolism studies
- Epigenetics and DNA Methylation
- Acute Lymphoblastic Leukemia research
- Tryptophan and brain disorders
- Single-cell and spatial transcriptomics
- Virus-based gene therapy research
- Immune Cell Function and Interaction
- Renal cell carcinoma treatment
- Immune cells in cancer
- Cancer Genomics and Diagnostics
- Genomics and Chromatin Dynamics
Novartis Institutes for BioMedical Research
2016-2021
Novartis (Switzerland)
2016-2021
When SUCNR1/GPR91-expressing macrophages are activated by inflammatory signals, they change their metabolism and accumulate succinate. In this study, we show that during activation, release succinate into the extracellular milieu. They simultaneously up-regulate GPR91, which functions as an autocrine paracrine sensor for to enhance IL-1β production. GPR91-deficient mice lack metabolic reduced macrophage activation production of antigen-induced arthritis. Succinate is abundant in synovial...
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....
Combination of functional epigenomics and single-cell CRISPR screens reveals that ER exerts its oncogenic role via downstream TFs.
Asparagine deprivation by l-asparaginase (L-ASNase) is an effective therapeutic strategy in acute lymphoblastic leukemia, with resistance occurring due to upregulation of ASNS, the only human enzyme synthetizing asparagine (Annu. Rev. Biochem.2006, 75 (1), 629-654). l-Asparaginase efficacy solid tumors limited dose-related toxicities (OncoTargets and Therapy 2017, pp 1413-1422). Large-scale loss function genetic vitro screens identified ASNS as a cancer dependency several malignancies...
Abstract Asparagine deprivation by L-Asparaginase (L-ASNase) is an effective therapeutic strategy in Acute Lymphoblastic Leukemia, with resistance occurring due to upregulation of ASNS, the only human enzyme synthetizing 1 . efficacy solid tumors limited dose-related toxicities 2 Large-scale loss function genetic vitro screens identified ASNS as a cancer dependency several malignancies 3,4 Here we evaluate potential targeting melanoma cells. While confirm in-vitro on silencing, this largely...