Daniel Álvarez‐Villanueva
A5076778474- Advanced Breast Cancer Therapies
- Cancer Treatment and Pharmacology
- Protein Degradation and Inhibitors
- NF-κB Signaling Pathways
- Cell Image Analysis Techniques
- Cancer, Hypoxia, and Metabolism
- CAR-T cell therapy research
- Cancer, Stress, Anesthesia, and Immune Response
- Chromatin Remodeling and Cancer
- Computational Drug Discovery Methods
- bioluminescence and chemiluminescence research
- Cancer Research and Treatments
- Ubiquitin and proteasome pathways
- Enzyme function and inhibition
- Immune Cell Function and Interaction
- 3D Printing in Biomedical Research
- interferon and immune responses
- Immune Response and Inflammation
- Genomics and Chromatin Dynamics
- Melanoma and MAPK Pathways
- Biological Research and Disease Studies
- T-cell and B-cell Immunology
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- Histone Deacetylase Inhibitors Research
Institut d'Investigació Biomédica de Bellvitge
2023-2025
Institut Català d'Oncologia
2023-2025
Centro de Investigación Biomédica en Red de Cáncer
2021-2025
Bellvitge University Hospital
2023-2025
Hospital Del Mar
2025
Hospital del Mar Research Institute
2021-2023
Abstract Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress response programs that counteract the inherent toxicity such aberrant signaling. Although inhibition signaling has been explored extensively, there is increasing evidence overactivation same can also disrupt cancer cause lethality. We show here protein phosphatase 2A (PP2A) hyperactivates multiple engages responses in colon cells. Genetic compound screens...
The DNA damage repair kinase ATM is phosphorylated by the NF-κB pathway IKKα, resulting in enhanced through nonhomologous end-joining pathway. Thus, inhibition of IKKα enhances efficacy cancer therapy based on inducing damage. Here, we found a role for IKK regulatory subunit NEMO mediated and IKKα. Exposure to damaging agents induced interaction with preformed ATM-IKKα complex, which was required target active chromatin efficient but not activating ATM. Recognition damaged IKKα-NEMO-ATM...
Abstract Current therapy against colorectal cancer (CRC) is based on DNA-damaging agents that remain ineffective in a proportion of patients. Whether and how non-curative DNA damage-based treatment affects tumor cell behavior patient outcome primarily unstudied. Using CRC patient-derived organoids (PDO)s, we show sublethal doses chemotherapy (CT) does not select previously resistant populations but induces quiescent state specifically to TP53 wildtype (WT) cells, which linked the acquisition...
Maintenance of pluripotency is a multifactorial process in which NF-κB negative regulator. Our previous work identified chromatin role for IκBα, the master regulator signaling, that critical proper regulation various tissue stem cells. Here, we found IκBα accumulates specifically fraction pluripotent embryonic depletion does not affect NF-kB-dependent transcription, but causes profound epigenetic rewiring cells, including alterations H3K27me3, histone mark catalyzed by Polycomb repression...
Maintenance of pluripotency is a multifactorial process in which NF-κB negative regulator. Our previous work identified chromatin role for IκBα, the master regulator signaling, that critical proper regulation various tissue stem cells. Here, we found IκBα accumulates specifically fraction pluripotent embryonic depletion does not affect NF-kB-dependent transcription, but causes profound epigenetic rewiring cells, including alterations H3K27me3, histone mark catalyzed by Polycomb repression...
<div>Abstract<p>Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress response programs that counteract the inherent toxicity such aberrant signaling. Although inhibition signaling has been explored extensively, there is increasing evidence overactivation same can also disrupt cancer cause lethality. We show here protein phosphatase 2A (PP2A) hyperactivates multiple engages responses in colon cells. Genetic...
Abstract We previously demonstrated that the NF-κB inhibitor IκBα binds chromatin together with PRC2 to regulate a subset of developmental- and stem cell-related genes. This alternative function has been elusive in both physiological disease conditions because predominant role as negative regulator NF-κB. here uniquely characterize specific residues allow generation separation-of-function (SOF) mutants are defective for either NF-κB-related (SOF ΔNF-κB ) or chromatin-related ΔH2A,H4...
<p>Figure S9: Single-cell RNAseq identify transcriptional signatures downregulated in CRC cells after acquired resistance to the combination of LB-100 and adavosertib UMAP representations HT-29 (A) SW-480 (B) colored by activity scores for indicated pathways. UMAPs sample origin from both cell lines are present left reference. The boxen plots show pathway parental (red) resistant (blue) cells.</p>
<p>Supplementary table 6: Stress-focused drug screens AUC differences in SW-480 cells Area Under the Curve (AUC) from each compound of stress-focused screen presence or absence LB-100. Compounds are ranked by difference between LB-100-treated and untreated samples.</p>
<p>Supplementary table 3: Full list of genes whose knockout attenuated LB-100 toxicity in SW-480 cells the CRISPR-KO screen FDR smaller or equal to 0.25 and log2 fold change greater 1 treated/untreated comparison were criteria for hit selection.</p>
<p>Supplementary table 1: Cancer cell lines with oncogenic drivers The mutational status of the was compiled from ATCC, Catalogue Somatic Mutations in (COSMIC) and Cell Model Passport, Wellcome Trust Sanger Institute, Depmap portal databases.</p>
<p>Supplementary table 4: The composition of the stress-focused drug library Compounds comprising with their respective targets.</p>
<p>Supplementary table 4: The composition of the stress-focused drug library Compounds comprising with their respective targets.</p>
<p>Figure S7: Normal tissues from the orthotopic CRC PDXs are not affected by LB-100, adavosertib, or combination. Representative Hematoxylin & Eosin (H&E) stainings of heart, liver, lung, and spleen PDOX1 treated as indicated. Original magnifications indicated.</p>
<p>Supplementary table 5: Stress-focused drug screens AUC differences in HT-29 cells Area Under the Curve (AUC) from each compound of stress-focused screen presence or absence LB-100. Compounds are ranked by difference between LB-100-treated and untreated samples.</p>
<p>Figure S9: Single-cell RNAseq identify transcriptional signatures downregulated in CRC cells after acquired resistance to the combination of LB-100 and adavosertib UMAP representations HT-29 (A) SW-480 (B) colored by activity scores for indicated pathways. UMAPs sample origin from both cell lines are present left reference. The boxen plots show pathway parental (red) resistant (blue) cells.</p>
<p>Figure S8: Acquired resistance to the combination of LB-100 and adavosertib suppressed malignant traits in CRC models (A) IncuCyte-based proliferation assays from HT-29 SW-480 parental resistant cells absence or presence (LB-100 4 µM + 400 nM). (B) Chromosome counting representative chromosome spreads cells. Nocodazole was added for 3h block mitosis. Cells were harvested by mitotic shake-off spreading. Over 40 (HT-29 HT-29-R) 50 (SW-480 SW-480-R) counted per cell line. Asterisks...
<p>Figure S7: Normal tissues from the orthotopic CRC PDXs are not affected by LB-100, adavosertib, or combination. Representative Hematoxylin & Eosin (H&E) stainings of heart, liver, lung, and spleen PDOX1 treated as indicated. Original magnifications indicated.</p>
<p>Supplementary table 7: Full list of genes whose knockout was selectively toxic in the presence LB-100 SW-480 cells CRISPR-KO screen FDR smaller or equal to 0.25 and log2 fold change -1 treated/untreated comparison were criteria for hit selection.</p>
<p>Supplementary table 2: Full list of genes whose overexpression was selectively toxic in the presence LB-100 HT-29 cells CRISPRa screen FDR smaller or equal to 0.25 and log2 fold change -1 treated/untreated comparison were criteria for hit selection.</p>
<p>Supplementary table 1: Cancer cell lines with oncogenic drivers The mutational status of the was compiled from ATCC, Catalogue Somatic Mutations in (COSMIC) and Cell Model Passport, Wellcome Trust Sanger Institute, Depmap portal databases.</p>
<p>Supplementary table 2: Full list of genes whose overexpression was selectively toxic in the presence LB-100 HT-29 cells CRISPRa screen FDR smaller or equal to 0.25 and log2 fold change -1 treated/untreated comparison were criteria for hit selection.</p>