A5024567417- Nuclear Structure and Function
- RNA Research and Splicing
- Mechanisms of cancer metastasis
- Plant Virus Research Studies
- DNA Repair Mechanisms
- PARP inhibition in cancer therapy
- Erythrocyte Function and Pathophysiology
- Enzyme Structure and Function
- Transgenic Plants and Applications
- Mitochondrial Function and Pathology
- interferon and immune responses
- Immunodeficiency and Autoimmune Disorders
- Cancer-related molecular mechanisms research
- Polyamine Metabolism and Applications
- Cancer-related Molecular Pathways
- Peptidase Inhibition and Analysis
- Trace Elements in Health
- Ubiquitin and proteasome pathways
- Chronic Myeloid Leukemia Treatments
- Vector-Borne Animal Diseases
- Acute Myeloid Leukemia Research
- Chronic Lymphocytic Leukemia Research
- SARS-CoV-2 and COVID-19 Research
- Retinal Development and Disorders
- Enzyme function and inhibition
Universidad Europea
2018-2023
Centro de Investigación en Red en Enfermedades Cardiovasculares
2019-2022
Spanish National Centre for Cardiovascular Research
2010-2022
Centro de Investigación Biomédica en Red
2020
Centro Nacional de Epidemiología
2009-2014
Achillion Pharmaceuticals (United States)
2014
Hospital General de México
2013
Universidad de Oviedo
2013
Spanish National Cancer Research Centre
2007-2011
Instituto de Biomedicina de Valencia
2010
Hutchinson-Gilford progeria syndrome (HGPS) is caused by a point mutation in the LMNA gene that activates cryptic donor splice site and yields truncated form of prelamin A called progerin. Small amounts progerin are also produced during normal aging. Studies with mouse models HGPS have allowed recent development first therapeutic approaches for this disease. However, none these earlier works addressed aberrant pathogenic splicing observed patients because lack an appropriate model. Here, we...
Hematopoietic stem cells (HSCs) residing in the bone marrow (BM) accumulate during aging but are functionally impaired. However, role of HSC-intrinsic and -extrinsic mechanisms remains debated. Megakaryocytes promote quiescence neighboring HSCs. Nonetheless, whether megakaryocyte-HSC interactions change pathological/natural is unclear. Premature Hutchinson-Gilford progeria syndrome recapitulates physiological features, these arise from altered or niche unknown. Here, we show that BM...
Progerin is a mutant form of lamin A responsible for Hutchinson-Gilford progeria syndrome (HGPS), premature aging disorder characterized by excessive atherosclerosis and vascular calcification that leads to death, predominantly myocardial infarction or stroke. The goal this study was investigate mechanisms cause in HGPS.We performed expression functional studies wild-type mice knock-in Lmna(G609G/+) expressing progerin, which mimic the main clinical manifestations HGPS. showed aortic...
Abstract The identification of novel approaches to specifically target the DNA-damage checkpoint response in chemotherapy-resistant cancer stem cells (CSC) solid tumors has recently attracted great interest. We show here colon cell lines and primary that inhibition checkpoint-modulating phosphoinositide 3-kinase-related (PIK) kinases preferentially depletes chemoresistant exclusively tumorigenic CD133+ fraction. observed a time- dose-dependent disproportionally pronounced loss consecutive...
A cDNA corresponding to the coding region of VP1, putative RNA-dependent RNA polymerase, infectious bursal disease virus (IBDV) was cloned and inserted into genome a vaccinia inducible expression vector. The molecular mass antigenic reactivity VP1 expressed in mammalian cells are identical those its counterpart IBDV-infected cells. results presented here demonstrate that is efficiently incorporated IBDV virus-like particles (VLPs) produced coexpressing polyprotein VP1. Incorporation VLPs...
Significance Defective prelamin A processing causes cardiovascular alterations and premature death in Hutchinson–Gilford progeria syndrome (HGPS) patients also occurs during physiological aging. We found overt repolarization abnormalities HGPS at advanced disease stages. Similar were present progeroid Zmpste24 −/− mice, which had cardiomyocytes that exhibited prolonged calcium transient duration reduced sarcoplasmic reticulum loading capacity release, consistent with absence of...
Abstract Changes in gene expression are produced cells as a consequence of virus infections. In the present work, we used proteomic technology to globally examine African swine fever (ASFV)‐infected Vero searching for infection‐associated proteins order determine target pathogenesis studies. We studied alterations cellular protein profile after ASFV infection by two‐dimensional electrophoresis, identifying modified matrix‐assisted laser desorption/ionization peptide mass fingerprinting. A...
ABSTRACT The DP71L protein of African swine fever virus (ASFV) shares sequence similarity with the herpes simplex ICP34.5 over a C-terminal domain. We showed that catalytic subunit phosphatase 1 (PP1) interacts specifically ASFV in yeast two-hybrid screen. chimeric full-length protein, from strain Badajoz 71 (BA71V), fused to glutathione S -transferase (DP71L-GST) was expressed Escherichia coli and shown bind PP1-α as histidine fusion (6×His-PP1α) E. . functional effects this interaction...
The breast cancer metastasis suppressor 1 (BRMS1) gene has been shown to suppress without affecting the growth of primary tumor in mouse models. It also tumors derived from breast, melanoma, and, more recently, ovarian carcinoma (see ref 1). However, how BRMS1 exerts its function remains unknown. To shed light into metastatic mechanism action, sensitive 2D-DIGE analysis coupled with MS used identify proteins differentially expressed by either overexpressing (Mel-BRMS1) or silencing (sh635) a...
A large body of evidence supports the hypothesis that proteasomal degradation growth suppressor p27Kip1 (p27) facilitates mammalian cell cycle progression. However, very few studies have addressed possibility proteasome-independent mechanisms p27 proteolysis. Here we provide for a novel pathway via lysosome is mediated by its interaction with endosomal protein sorting nexin 6 (SNX6), member family vesicular trafficking regulators. and SNX6 interact in vitro vivo cells, partially colocalize...
Breast cancer metastasis suppressor 1 (BRMS1) reduces the number and size of secondary tumours in a mouse model without affecting growth primary foci upon its re-expression. Knockdown BRMS1 expression associates with metastasis. The molecular details on mechanism action include ability to function as transcriptional co-repressor consistently has been described predominantly nuclear protein. Since cellular distribution could represent potential regulation, we wanted characterize sequence...
Sorting nexin 6 (SNX6), a predominantly cytoplasmic protein involved in intracellular trafficking of membrane receptors, was identified as TGF-β family interactor. However, apart from being component the Retromer, little is known about SNX6 cellular functions. Pim-1-dependent nuclear translocation has been reported suggesting putative role for SNX6. Here, we describe previously non-reported association with breast cancer metastasis suppressor 1 (BRMS1) detected by yeast two-hybrid screening....
BCR-ABL is an aberrant tyrosine kinase responsible for chronic myeloid leukemia (CML). Tyrosine inhibitors (TKIs) induce a potent antileukemic response mostly based on the inhibition of BCR-ABL, but they also increase activity Natural Killer (NK) and CD8+ T cells. After several years, patients may interrupt treatment due to sustained, deep molecular response. By unknown reasons, half relapse during interruption, whereas others maintain control residual leukemic cells years. In this study,...
The continuous relationship between blood pressure (BP) and cardiovascular events makes the distinction elevated BP hypertension based on arbitrary cut-off values for BP. Even mild elevations manifesting as high-normal have been associated with risk. We hypothesize that persistent increases atherosclerotic plaque development. To evaluate this causal link, we developed a new mouse model of adeno-associated virus (AAV) gene transfer. constructed AAV vectors to support transfer
Aging is the main risk factor for cardiovascular and metabolic diseases, which have become a global concern as world population ages. These diseases aging process are exacerbated in Hutchinson-Gilford progeria syndrome (HGPS or progeria). Here, we evaluated cardiometabolic disease animal models of premature normal with aim identifying alterations that shared specific to each condition. Despite differences body composition markers, prematurely normally mice developed heart failure similar...
Selenium nanoparticles (SeNPs) have been receiving special attention in recent years due to their antioxidant capacity and antitumor properties. However, the mechanisms associated with these properties remain be elucidated. For this reason, a global transcriptome analysis has designed work it was carried out using human hepatocarcinoma cells chitosan-stabilized SeNPs (Ch-SeNPs) identify new targets pathways related Ch-SeNPs. The results obtained confirm alteration of cell cycle effect...
The Notch pathway has been linked to pulmonary hypertension, but its role in systemic hypertension and, particular left ventricular hypertrophy (LVH), remains poorly understood. main objective of this work was analyse the effect inhibiting on establishment and maintenance angiotensin II (Ang-II)-induced arterial LVH adult mice with inducible genetic deletion γ-secretase, test preclinically therapeutic efficacy γ-secretase inhibitors (GSIs).We analysed Ang-II responses primary cultures...