- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- SARS-CoV-2 and COVID-19 Research
- Computational Drug Discovery Methods
- Receptor Mechanisms and Signaling
- COVID-19 Clinical Research Studies
- PARP inhibition in cancer therapy
- Viral Infections and Immunology Research
- Sirtuins and Resveratrol in Medicine
- Signaling Pathways in Disease
- Endoplasmic Reticulum Stress and Disease
- Viral gastroenteritis research and epidemiology
- CRISPR and Genetic Engineering
- Neuroscience and Neural Engineering
- Semiconductor materials and devices
- Potassium and Related Disorders
- Radiopharmaceutical Chemistry and Applications
- Immune Cell Function and Interaction
- Medical Imaging Techniques and Applications
- Nicotinic Acetylcholine Receptors Study
- Ion Transport and Channel Regulation
- HIV Research and Treatment
- Synthesis and Biological Evaluation
- Ubiquitin and proteasome pathways
- Autophagy in Disease and Therapy
Universitat de Barcelona
2013-2023
Gladstone Institutes
2020-2022
University of California, San Francisco
2020-2022
Institute for Biomedicine
2013
Brain Physiology Lab
2013
Abstract The novel SARS-CoV-2 virus emerged in December 2019 and has few effective treatments. We applied a computational drug repositioning pipeline to differential gene expression signatures derived from publicly available data. utilized three independent published studies acquire or generate lists of differentially expressed genes between control SARS-CoV-2-infected samples. Using rank-based pattern matching strategy based on the Kolmogorov–Smirnov Statistic, were queried against profiles...
The replication of SARS-CoV-2 and other coronaviruses depends on transcription negative-sense RNA intermediates that serve as the templates for synthesis positive-sense genomic (gRNA) multiple different subgenomic mRNAs (sgRNAs) encompassing fragments arising from discontinuous transcription. Recent studies have aimed to characterize expression transcripts in order investigate their clinical significance. Here, we describe a novel panel reverse droplet digital PCR (RT-ddPCR) assays designed...
SARS-CoV-2 non-structural protein Nsp14 is a highly conserved enzyme necessary for viral replication. forms stable complex with Nsp10 and exhibits exoribonuclease N7-methyltransferase activities. Protein-interactome studies identified human sirtuin 5 (SIRT5) as putative binding partner of Nsp14. SIRT5 an NAD-dependent deacylase critical cellular metabolism that removes succinyl malonyl groups from lysine residues. Here we investigated the nature this interaction role during infection. We...
Kv, which play a role in the immune system, are remodeled during carcinogenesis. Leukocytes present limited Kv repertoire, with Kv1.3 and Kv1.5 as isoforms that involved neoplastic processes, such proliferation migration. In this study, we identified B-lymphocytes, characterized its migration, analyzed expression human non-Hodgkin lymphomas. DLBCL, F, MCL, ALCL, T, along control N specimens, were analyzed. found to be differentially; whereas did not correlate state of dedifferentiation or...
A hallmark of coronavirus transcription is the generation negative-sense RNA intermediates that serve as templates for synthesis positive-sense genomic (gRNA) and an array subgenomic mRNAs (sgRNAs) encompassing sequences arising from discontinuous transcription. Existing PCR-based diagnostic assays SAR-CoV-2 are qualitative or semi-quantitative do not provide resolution needed to assess complex dynamics SARS-CoV-2 over course infection. We developed validated a novel panel sensitive,...
Impairment of Kv1.3 expression at the cell membrane in leukocytes and sensory neuron contributes to pathophysiology autoimmune diseases syndromes. Molecular mechanisms underlying channel trafficking plasma remain elusive. We report a novel non-canonical di-acidic signal (E483/484) C-terminus essential for anterograde transport surface expression. Notably, homologous motifs are conserved neuronal Kv1 Shaker channels. Biochemical analysis revealed interactions with Sec24 subunit coat protein...
Abstract The voltage-dependent potassium channel Kv1.3 plays essential physiological functions in the immune system. Kv1.3, regulating membrane potential, facilitates downstream Ca 2+ -dependent pathways and becomes concentrated specific microdomains that serve as signaling platforms. Increased and/or delocalized expression of is observed at onset several autoimmune diseases. In this work, we show adenosine (ADO), which a potent endogenous modulator, stimulates PKC, thereby causing...
ABSTRACT The voltage-dependent K+ channel Kv1.3 (also known as KCNA3), which plays crucial roles in leukocytes, physically interacts with KCNE4. This interaction inhibits the currents because is retained within intracellular compartments. Thus, KCNE subunits are regulators of channels immune system. Although canonical interactions Kv7 under intensive investigation, molecular determinants governing important Kv1.3– KCNE4 association system unknown. Our results suggest that tertiary structure...
Abstract SARS-CoV-2 non-structural protein Nsp14 is a highly conserved enzyme necessary for viral replication. forms stable complex with Nsp10 and exhibits exoribonuclease N7-methyltransferase activities. Protein-interactome studies identified human sirtuin 5 (SIRT5) as putative binding partner of Nsp14. SIRT5 an NAD-dependent deacylase critical cellular metabolism that removes succinyl malonyl groups from lysine residues. Here we investigated the nature this interaction role during...
Abstract The voltage-dependent potassium channel Kv1.3 plays essential roles in the immune system, participating leukocyte activation, proliferation and apoptosis. regulatory subunit KCNE4 acts as an ancillary peptide of Kv1.3, modulates K + currents controls abundance at cell surface. KCNE4-dependent regulation oligomeric complex fine-tunes physiological role Kv1.3. Thus, is crucial for Ca 2+ -dependent Kv1.3-related functions. To better understand we manipulated its expression various...
Voltage-dependent K (+) (Kv) channels are tightly regulated during the immune system response. Leukocytes have a limited repertoire of Kv channels, whose physiological role is under intense investigation. A functional channel an oligomeric complex composed pore-forming and ancillary subunits. The KCNE gene family novel group modulatory elements in leukocytes. Here, we characterized expression KCNEs (1-5) leukocytes investigated their regulation leukocyte proliferation mode activation. Murine...
The voltage-dependent potassium (Kv) channel Kv1.3 regulates leukocyte proliferation, activation, and apoptosis, altered expression of this is linked to autoimmune diseases. Thus, the fine-tuning function crucial for immune system response. accessory protein, voltage-gated subfamily E (KCNE) subunit 4, acts as a dominant negative regulatory both enhance inactivation induce intracellular retention Kv1.3. Mutations in KCNE4 also cause dysfunction. Although formation Kv1.3-KCNE4 complexes has...
The voltage-gated potassium channel Kv1.3 plays a crucial role during the immune response. forms oligomeric complexes by associating with several modulatory subunits. KCNE4, one of five members KCNE family, binds to Kv1.3, altering activity and membrane expression. association KCNEs Kv channels is subject numerous studies, stoichiometry such associations has led an ongoing debate. number KCNE4 subunits that can interact modulate unknown. transfers important elements channelosome negatively...
Abstract The novel SARS-CoV-2 virus emerged in December 2019 and has few effective treatments. We applied a computational drug repositioning pipeline to differential gene expression signatures derived from publicly available data. utilized three independent published studies acquire or generate lists of differentially expressed genes between control SARS-CoV-2-infected samples. Using rank-based pattern matching strategy based on the Kolmogorov-Smirnov Statistic, were queried against profiles...
Abstract Quiescence is a hallmark of CD4 + T cells latently infected with HIV-1. While reversing this quiescence an effective approach to reactivate latent HIV from in culture, it can cause deleterious cytokine dysregulation patients. Here we report that FOXO1, key regulator T-cell quiescence, promotes latency and suppresses productive infection. In resting cells, FOXO1 inhibition induces ER stress activates two associated transcription factors: activating factor 4 (ATF4) nuclear activated...
The novel SARS-CoV-2 virus emerged in December 2019 and has few effective treatments. We applied a computational drug repositioning pipeline to differential gene expression signatures derived from publicly available data. utilized three independent published studies acquire or generate lists of differentially expressed genes between control SARS-CoV-2-infected samples. Using rank-based pattern matching strategy based on the Kolmogorov-Smirnov Statistic, were queried against profiles...
Abstract The exact mechanism of coronavirus replication and transcription is not fully understood; however, a hallmark the generation negative-sense RNA intermediates that serve as templates for synthesis positive-sense genomic (gRNA) an array subgenomic mRNAs (sgRNAs) encompassing sequences arising from discontinuous transcription. Existing PCR-based diagnostic assays SAR-CoV-2 are qualitative or semi-quantitative do provide resolution needed to assess complex dynamics SARS-CoV-2 over...