Claudio R Santos

Claudio R Santos
London Research Institute

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23
Publications
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10,088
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Publications

Publications (23)
Article
Full-text available
Background Candidate biomarkers have been identified for clear cell renal cell carcinoma (ccRCC) patients, but most have not been validated. Objective To validate published ccRCC prognostic biomarkers in an independent patient cohort and to assess intratumour heterogeneity (ITH) of the most promising markers to guide biomarker optimisation. Des...
Article
Full-text available
Clear cell renal carcinomas (ccRCCs) can display intratumor heterogeneity (ITH). We applied multiregion exome sequencing (M-seq) to resolve the genetic architecture and evolutionary histories of ten ccRCCs. Ultra-deep sequencing identified ITH in all cases. We found that 73-75% of identified ccRCC driver aberrations were subclonal, confounding esti...
Conference Paper
Background: Current efforts to define the genomic landscapes of solid tumours are based on the analysis of single tumour biopsies. We recently demonstrated through multi-region exome sequencing (M-seq) of 2 ccRCC that these cancers are genetically heterogeneous (Gerlinger et al. NEJM, 2012). Thus, single biopsy approaches are likely to underestimat...
Article
Full-text available
Clear cell renal cell carcinoma (ccRCC) is the most common pathological subtype of kidney cancer. Here, we integrated an unbiased genome-wide RNA interference screen for ccRCC survival regulators with an analysis of recurrently overexpressed genes in ccRCC to identify new therapeutic targets in this disease. One of the most potent survival regulato...
Article
Lipids form a diverse group of water-insoluble molecules that include triacylglycerides, phosphoglycerides, sterols and sphingolipids. They play several important roles at cellular and organismal levels. Fatty acids are the major building blocks for the synthesis of triacylglycerides, which are mainly used for energy storage. Phosphoglycerides, tog...
Article
Full-text available
Unlabelled: Alterations in metabolic activity contribute to the proliferation and survival of cancer cells. We investigated the effect of siRNA-mediated gene silencing of 222 metabolic enzymes, transporters, and regulators on the survival of 3 metastatic prostate cancer cell lines and a nonmalignant prostate epithelial cell line. This approach rev...
Article
Full-text available
Intratumor heterogeneity may foster tumor evolution and adaptation and hinder personalized-medicine strategies that depend on results from single tumor-biopsy samples. To examine intratumor heterogeneity, we performed exome sequencing, chromosome aberration analysis, and ploidy profiling on multiple spatially separated samples obtained from primary...
Article
Viral infections cause a major stress in host cells. The cellular responses to stress are mediated by p53, which by deregulation of cell cycle and apoptosis, may also be part of the host cell reaction to fight infections. Therefore, during evolutionary viral adaptation to host organisms, viruses have developed strategies to manipulate host cell p53...
Article
Full-text available
In recent years several reports have linked mTORC1 (mammalian target of rapamycin complex 1) to lipogenesis via the SREBPs (sterol-regulatory-element-binding proteins). SREBPs regulate the expression of genes encoding enzymes required for fatty acid and cholesterol biosynthesis. Lipid metabolism is perturbed in some diseases and SREBP target genes,...
Article
The SREBP family of transcription factors regulates the expression of genes involved in fatty acid and cholesterol biosynthesis. The activation of SREBP transcription factors requires proteolytic cleavage of the inactive precursor and nuclear translocation of the mature form of the protein. It has been shown that nuclear accumulation of the mature...
Article
Full-text available
Cell growth requires co-ordinated regulation of processes that provide metabolites for the synthesis of macromolecules such as proteins and membrane lipids. In recent years, a lot of emphasis has been placed on the activation of protein synthesis by mTORC1 (mammalian target of rapamycin complex 1). The contribution of anabolic pathways other than p...
Article
Full-text available
Cell growth (accumulation of mass) needs to be coordinated with metabolic processes that are required for the synthesis of macromolecules. The PI3-kinase/Akt signaling pathway induces cell growth via activation of complex 1 of the target of rapamycin (TORC1). Here we show that Akt-dependent lipogenesis requires mTORC1 activity. Furthermore, nuclear...
Article
Full-text available
Cellular biological responses to specific stimulation are determined by a balance among signaling pathways. Protein interactions are likely to modulate these pathways. Vaccinia-related kinase-2 (VRK2) is a novel human kinase that can modulate different signaling pathways. We report that in vivo, the activity of JIP1-JNK complexes is downregulated b...
Article
Full-text available
Viruses have to adjust to the host cell to guarantee their life cycle and survival. This aspect of the virus-host cell interaction is probably performed by viral proteins, such as serine-threonine kinases, that are present early during infection. Vaccinia virus has an early Ser-Thr kinase, B1R, which, although required for successful viral infectio...
Article
Full-text available
The vaccinia-related kinase (VRK) proteins are a new family with three members in the human kinome. The VRK1 protein phosphorylates several transcription factors and has been postulated to be involved in regulation of cell proliferation. In normal squamous epithelium, VRK1 is expressed in the proliferation area. Because VRK1 can stabilize p53, the...
Article
Full-text available
The VRK1 kinase is a novel Ser-Thr kinase in the human kinome that diverged from the casein kinase 1 branch. These kinases phosphorylate transcription factors related to stress responses, such as p53. In this report we have studied the phosphorylation of the transcription factor c-Jun in its N-terminal region. The VRK1 protein phosphorylates c-Jun...
Article
Poxvirus infection has a strong effect on cellular functions. To understand viral pathogenesis, it is necessary to know how viral proteins interact with host proteins. The B1R kinase is an early viral gene required for vaccinia virus DNA synthesis and replication, but no cellular substrate is known for this viral kinase. B1R is able to hyperphospho...
Article
Full-text available
In the human kinome, vaccinia-related kinase-1 (VRK1) is a new Ser-Thr kinase associated with proliferating tissues. VRK1 colocalizes with ATF2 in the nucleus and can form a stable complex. We have studied the phosphorylation of the transcription factor ATF2, which regulates gene expression by forming dimers with proteins with basic region-leucine...

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