A5077812243- Cutaneous lymphoproliferative disorders research
- CAR-T cell therapy research
- Toxin Mechanisms and Immunotoxins
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- interferon and immune responses
- Cytokine Signaling Pathways and Interactions
- Colorectal Cancer Treatments and Studies
- Cancer, Hypoxia, and Metabolism
- NF-κB Signaling Pathways
- Cancer Research and Treatments
- Fungal Infections and Studies
- Cell death mechanisms and regulation
- Cancer-related Molecular Pathways
- Acute Myeloid Leukemia Research
- Lung Cancer Treatments and Mutations
- RNA modifications and cancer
- CNS Lymphoma Diagnosis and Treatment
- Lymphoma Diagnosis and Treatment
- Melanoma and MAPK Pathways
- RNA Interference and Gene Delivery
- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
- Heat shock proteins research
- Single-cell and spatial transcriptomics
Dana-Farber Cancer Institute
2016-2021
Harvard University
2016-2021
University of Pennsylvania
2013-2017
Universidad de Oviedo
2007-2014
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematologic malignancy with dismal outcomes for which no standard therapy exists. We found that primary BPDCN cells were dependent on the antiapoptotic protein BCL2 and uniformly sensitive to inhibitor venetoclax, as measured by direct cytotoxicity, apoptosis assays, dynamic BH3 profiling. Animals bearing patient-derived xenografts had disease responses improved survival after venetoclax treatment in vivo Finally, we...
Chromatin organization is a highly orchestrated process that influences gene expression, in part by modulating access of regulatory factors to DNA and nucleosomes. Here, we report the chromatin accessibility regulator HMGN1, target recurrent copy gains leukemia, controls myeloid differentiation. HMGN1 amplification associated with increased accessibility, histone H3K27 acetylation loci important for hematopoietic stem cells (HSCs) such as HoxA cluster genes. In vivo, overexpression linked...
Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive leukemia of cells (pDC). BPDCN occurs at least three times more frequently in men than women, but the reasons for this sex bias are unknown. Here, studying genomics primary and modeling disease-associated mutations, we link acquired alterations RNA splicing to abnormal pDC development inflammatory response through Toll-like receptors. Loss-of-function mutations ZRSR2, X chromosome gene encoding a factor, enriched...
Down syndrome (DS, trisomy 21) is associated with developmental abnormalities and increased leukemia risk. To reconcile chromatin alterations transcriptome changes, we performed paired exogenous spike-in normalized RNA immunoprecipitation sequencing in DS models. Absolute normalization unmasks global amplification of gene expression 21. Overexpression the nucleosome binding protein HMGN1 (encoded on chr21q22) recapitulates transcriptional changes seen triplication a critical region distal...
Abstract Hip fractures (HFx) are associated with a higher morbidity and mortality rates, leading to significant reduction in life quality limitation of patient´s mobility. The present study aimed obtain real-world evidence on the clinical characteristics patients an initial second hip fracture develop predictive model for HFx using artificial intelligence. Electronic health records from one hospital centre Spain January 2011 December 2019 were analysed EHRead® technology, based natural...
Tumor necrosis factor receptor 2 (TNFR2) activates transcription κB (NF-κB) and c-Jun N-terminal kinase (JNK). The mechanisms mediating these activations are dependent on the recruitment of TNF receptor-associated (TRAF2) to intracellular region receptor. TNFR2 also induces TRAF2 degradation. We show that in addition well characterized binding motif 402-SKEE-405, human contains another sequence located at C-terminal end (amino acids 425-439), which recruits NF-κB. In that, a conserved...
Tumor Necrosis Factor (TNF) interacts with two receptors known as TNFR1 and TNFR2. activation may result in either cell proliferation or death. TNFR2 activates Nuclear Factor-kappaB (NF-kB) c-Jun N-terminal kinase (JNK) which lead to transcriptional of genes related survival. This depends on the binding TNF Receptor Associated 2 (TRAF2) receptor. also induces TRAF2 degradation. In this work we have investigated structural features responsible for inducing degradation studied biological...
We showed previously that in HT29 colon cancer cells, modulation of hypoxia-induced stress signaling affects oxaliplatin cytotoxicity. To further study the significance through JNK, we set out to investigate how kinase activities influences cellular responses hypoxic cells cytotoxic drugs.In a panel cell lines, investigated effects pharmacologic and molecular inhibition JNK on sensitivity oxaliplatin, SN-38, 5-FU. Combination studies for drugs inhibitor CC-401 were carried vitro...
Abstract Elucidation of TNF-directed mechanisms for cell death induction and maintenance tumor growth has revealed a role receptor-interacting protein kinases 1 3 (RIPK1/RIP1 RIPK3/RIP3), components the necrosome complex, as determinants fate. Here, participation TNF signaling was analyzed with regard to cytotoxic action different DNA-damaging agents in panel colon cancer cells. While most these lines were insensitive TNF, combination drugs increased sensitivity by inducing DNA damage,...
ABSTRACT Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive leukemia of cells (pDCs). BPDCN occurs at least three times more frequently in men than women, but the reasons for this sex bias are unknown. Here, studying genomics primary and modeling disease-associated mutations, we link acquired alterations RNA splicing to abnormal pDC development inflammatory response through Toll-like receptors. Loss-of-function mutations ZRSR2, X chromosome gene encoding a factor, enriched...
Microtubule interfering agents (MIAs) are antitumor drugs that inhibit microtubule dynamics, while kinesin spindle protein (KSP) inhibitors substances block the formation of bipolar during mitosis. All these compounds cause accumulation mitotic cells and subsequently cell death. We used two-dimensional gel electrophoresis (2DE) followed by MALDI-MS analysis to demonstrate MIAs vinblastine (Velban) paclitaxel (Taxol), as well KSP inhibitor S-tritil-L-cysteine, induce phosphorylation annexin...
Paclitaxel (Ptx) is an antitumoural drug that inhibits microtubule dynamics, causes G2/M arrest and induces cell death. 2-D PAGE MALDI-TOF-MS analysis of HeLa cells extracts revealed Ptx up-regulates a form the eukaryotic elongation factor 1Bgamma (eEF1Bgamma) down-regulates another one. This event, linked to lack effect over eEF1Bgamma mRNA or protein levels suggested PTM this factor. Further followed by phosphospecific staining with PRO-Q Diamond showed up-regulated only. Moreover,...
Abstract BACKGROUND: We have shown that hypoxia induces signaling through stress pathways in the HT29 colon adenocarcinoma cell line, and modulation of MKK4/MKK7 exerts opposite effects on oxaliplatin cytotoxicity under hypoxic conditions: higher sensitivity when MKK4 function is impaired resistance MKK7 down- regulated. also observed differential JNK1 JNK2 cells to treatment which implied a pro-survival for JNK1. PURPOSE: Here we investigate how modulating JNK influences oxaliplatin, SN-38...
Abstract BACKGROUND: TNF is a dual role cytokine involved both in cell death and survival that expressed the tumor microenvironment. However, little known about molecular events mark biological outcomes of such opposite events. Recently, protein kinase RIP1 has been identified as new intermediate responses activated after DNA damage induction. PURPOSE: In this study we investigated how modulates sensitivity to SN38 colon cancer lines. We focused further on HT29- HCT116-derived lines which or...
<div>Abstract<p><b>Purpose:</b> We showed previously that in HT29 colon cancer cells, modulation of hypoxia-induced stress signaling affects oxaliplatin cytotoxicity. To further study the significance through JNK, we set out to investigate how kinase activities influences cellular responses hypoxic cells cytotoxic drugs.</p><p><b>Experimental Design:</b> In a panel cell lines, investigated effects pharmacologic and molecular inhibition JNK on...
<div>Abstract<p><b>Purpose:</b> We showed previously that in HT29 colon cancer cells, modulation of hypoxia-induced stress signaling affects oxaliplatin cytotoxicity. To further study the significance through JNK, we set out to investigate how kinase activities influences cellular responses hypoxic cells cytotoxic drugs.</p><p><b>Experimental Design:</b> In a panel cell lines, investigated effects pharmacologic and molecular inhibition JNK on...