ORCID Profile
0000-0001-7241-9044
Current Organisations
Universidad de La Laguna Departamento de Astrofísica
,
Universidad Complutense de Madrid Facultad de Ciencias Físicas
,
Consejo Superior de Investigaciones Científicas
,
Centro de Astrobiología
,
University of Toronto
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Publications
JWST NIRCam + NIRSpec: interstellar medium and stellar populations of young galaxies with rising star formation and evolving gas reservoirs
Publisher: Oxford University Press (OUP)
Date: 10-05-2023
Abstract: We present an interstellar medium and stellar population analysis of three spectroscopically confirmed z & 7 galaxies in the Early Release Observations JWST/NIRCam and JWST/NIRSpec data of the SMACS J0723.3−7327 cluster. We use the Bayesian spectral energy distribution-fitting code prospector with a flexible star formation history (SFH), a variable dust attenuation law, and a self-consistent model of nebular emission (continuum and emission lines). Importantly, we self-consistently fit both the emission line fluxes from JWST/NIRSpec and the broad-band photometry from JWST/NIRCam, taking into account slit-loss effects. We find that these three z=7.6–8.5 galaxies (M⋆ ≈ 108 M⊙) are young with rising SFHs and mass-weighted ages of 3–4 Myr, though we find indications for underlying older stellar populations. The inferred gas-phase metallicities broadly agree with the direct metallicity estimates from the auroral lines. The galaxy with the lowest gas-phase metallicity (Zgas= 0.06 Z⊙) has a steeply rising SFH, is very compact (& .2 kpc), and has a high star formation rate surface density (ΣSFR ≈ 22 M⊙ yr−1 kpc−2), consistent with rapid gas accretion. The two other objects with higher gas-phase metallicities show more complex multicomponent morphologies on kpc scales, indicating that their recent increase in star formation rate is driven by mergers or internal, gravitational instabilities. We discuss effects of assuming different SFH priors or only fitting the photometric data. Our analysis highlights the strength and importance of combining JWST imaging and spectroscopy for fully assessing the nature of galaxies at the earliest epochs.
Gβ 4 γ 1 as a modulator of M3 muscarinic receptor signalling and novel roles of Gβ 1 subunits in the modulation of cellular signalling
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.CELLSIG.2015.04.007
Abstract: Much is known about the how Gβγ subunits regulate effectors in response to G protein-coupled receptor stimulation. However, there is still a lot we don't know about how specific combinations of Gβ and Gγ are wired into different signalling pathways. Here, using an siRNA screen for different Gβ and Gγ subunits, we examined an endogenous M3 muscarinic receptor signalling pathway in HEK 293 cells. We observed that Gβ(4) subunits were critical for calcium signalling and a downstream surrogate measured as ERK1/2 MAP kinase activity. A number of Gγ subunits could partner with Gβ(4) but the best coupling was seen via Gβ(4)γ(1). Intriguingly, knocking down Gβ(1) actually increased signalling through the M3-mAChR most likely via an increase in Gβ(4) levels. We noted that Gβ(1) occupies the promoter of Gβ(4) and may participate in maturation of its mRNA. This highlights a new role for Gβγ signalling beyond their canonical roles in cellular signalling.
Novel, Gel-free Proteomics Approach Identifies RNF5 and JAMP as Modulators of GPCR Stability
Publisher: The Endocrine Society
Date: 08-2013
DOI: 10.1210/ME.2013-1091
JADES: Discovery of extremely high equivalent width Lyman-α emission from a faint galaxy within an ionized bubble at z = 7.3
Publisher: EDP Sciences
Date: 10-2202
ARGLU1 is a transcriptional coactivator and splicing regulator important for stress hormone signaling and development
Publisher: Oxford University Press (OUP)
Date: 30-01-2019
DOI: 10.1093/NAR/GKZ010
Genome-wide CRISPR screens reveal a Wnt–FZD5 signaling circuit as a druggable vulnerability of RNF43-mutant pancreatic tumors
Publisher: Springer Science and Business Media LLC
Date: 21-11-2016
DOI: 10.1038/NM.4219
Abstract: Forward genetic screens with CRISPR-Cas9 genome editing enable high-resolution detection of genetic vulnerabilities in cancer cells. We conducted genome-wide CRISPR-Cas9 screens in RNF43-mutant pancreatic ductal adenocarcinoma (PDAC) cells, which rely on Wnt signaling for proliferation. Through these screens, we discovered a unique requirement for a Wnt signaling circuit: engaging FZD5, one of the ten Frizzled receptors encoded in the human genome. Our results uncover an underappreciated level of context-dependent specificity at the Wnt receptor level. We further derived a panel of recombinant antibodies that reports the expression of nine FZD proteins and confirms that FZD5 functional specificity cannot be explained by protein expression patterns. Additionally, antibodies that specifically bind FZD5 and FZD8 robustly inhibited the growth of RNF43-mutant PDAC cells grown in vitro and as xenografts in vivo, providing orthogonal support for the functional specificity observed genetically. Proliferation of a patient-derived PDAC cell line harboring an RNF43 variant was also selectively inhibited by the FZD5 antibodies, further demonstrating their use as a potential targeted therapy. Tumor organoid cultures from colorectal carcinoma patients that carried RNF43 mutations were also sensitive to the FZD5 antibodies, highlighting the potential generalizability of these findings beyond PDAC. Our results show that CRIPSR-based genetic screens can be leveraged to identify and validate cell surface targets for antibody development and therapy.
A synthetic anti-Frizzled antibody engineered for broadened specificity exhibits enhanced anti-tumor properties
Publisher: Informa UK Limited
Date: 25-09-2018
Spectroscopic confirmation of four metal-poor galaxies at z = 10.3–13.2
Publisher: Springer Science and Business Media LLC
Date: 04-04-2023
Tandem Affinity Purification to Identify Cytosolic and Nuclear Gβγ-Interacting Proteins
Publisher: Springer New York
Date: 20-09-2014
DOI: 10.1007/978-1-4939-1755-6_14
Abstract: It has become clear in recent years that the Gβγ subunits of heterotrimeric proteins serve broad roles in the regulation of cellular activity and interact with many proteins in different subcellular locations including the nucleus. Protein affinity purification is a common method to identify and confirm protein interactions. When used in conjugation with mass spectrometry it can be used to identify novel protein interactions with a given bait protein. The tandem affinity purification (TAP) technique identifies partner proteins bound to tagged protein bait. Combined with protocols to enrich the nuclear fraction of whole cell lysate through sucrose cushions, TAP allows for purification of interacting proteins found specifically in the nucleus. Here we describe the use of the TAP technique on cytosolic and nuclear lysates to identify candidate proteins, through mass spectrometry, that bind to Gβ1 subunits.
Carbonaceous dust grains seen in the first billion years of cosmic time
Publisher: Springer Science and Business Media LLC
Date: 19-07-2023
YB-1 is elevated in medulloblastoma and drives proliferation in Sonic hedgehog-dependent cerebellar granule neuron progenitor cells and medulloblastoma cells
Publisher: Springer Science and Business Media LLC
Date: 04-01-2016
DOI: 10.1038/ONC.2015.491
Identification and properties of intense star-forming galaxies at redshifts z > 10
Publisher: Springer Science and Business Media LLC
Date: 04-04-2023
Copper bioavailability is a KRAS-specific vulnerability in colorectal cancer
Publisher: Springer Science and Business Media LLC
Date: 24-07-2020
DOI: 10.1038/S41467-020-17549-Y
Abstract: Despite its importance in human cancers, including colorectal cancers (CRC), oncogenic KRAS has been extremely challenging to target therapeutically. To identify potential vulnerabilities in KRAS-mutated CRC, we characterize the impact of oncogenic KRAS on the cell surface of intestinal epithelial cells. Here we show that oncogenic KRAS alters the expression of a myriad of cell-surface proteins implicated in erse biological functions, and identify many potential surface-accessible therapeutic targets. Cell surface-based loss-of-function screens reveal that ATP7A, a copper-exporter upregulated by mutant KRAS, is essential for neoplastic growth. ATP7A is upregulated at the surface of KRAS-mutated CRC, and protects cells from excess copper-ion toxicity. We find that KRAS-mutated cells acquire copper via a non-canonical mechanism involving macropinocytosis, which appears to be required to support their growth. Together, these results indicate that copper bioavailability is a KRAS-selective vulnerability that could be exploited for the treatment of KRAS-mutated neoplasms.
Progesterone Receptor Membrane Component 1 Is a Functional Part of the Glucagon-like Peptide-1 (GLP-1) Receptor Complex in Pancreatic β Cells
Publisher: Elsevier BV
Date: 11-2014
Ubiquitination and activation of a Rab GTPase promoted by a β2-Adrenergic Receptor/HACE1 complex
Publisher: The Company of Biologists
Date: 2013
DOI: 10.1242/JCS.132944
Abstract: We and others have shown that trafficking of G protein-coupled receptors is regulated by Rab GTPases. Cargo-mediated regulation of vesicular transport has received great attention lately. Rab GTPases, forming the largest branch of the Ras GTPase superfamily, regulate almost every step of vesicle-mediated trafficking. Rab GTPases are well-recognized targets of human diseases but their regulation and the mechanisms connecting them to cargo proteins are still poorly understood. Herein, we show by overexpression/depletion studies that HACE1, a HECT domain-containing ubiquitin ligase, promotes the recycling of the β2-adrenergic receptor (β2AR), a prototypical G protein-coupled receptor, through a Rab11a-dependent mechanism. Interestingly, the β2AR in conjunction with HACE1 triggered ubiquitination of Rab11a, as observed by Western blot analysis. LC-MS/MS experiments determined that Rab11a is ubiquitnatied on Lys145. A Rab11a-K145R mutant failed to undergo β2AR/HACE1-induced ubiquitination and inhibited the HACE1-mediated recycling of the β2AR. Rab11a, but not Rab11a-K145R, was activated by β2AR/HACE1 indicating that ubiquitination of Lys145 is involved in Rab11a activation. β2AR/HACE1 co-expression also potentiated ubiquitination of Rab6a and Rab8a, but not of other Rab GTPases that were tested. We report a novel regulatory mechanism of Rab GTPases by their ubiquitination with associated functional effects demonstrated on Rab11a. This partakes into a new pathway whereby a cargo protein, like a G protein-coupled receptor, can regulate its own trafficking by inducing the ubiquitination and activation of a Rab GTPase.
Physics of ULIRGs with MUSE and ALMA: The PUMA project
Publisher: EDP Sciences
Date: 06-2022
DOI: 10.1051/0004-6361/202142659
Abstract: Context. A classical scenario suggests that ultra-luminous infrared galaxies (ULIRGs) transform colliding spiral galaxies into a spheroid-dominated early-type galaxy. Recent high-resolution simulations have instead shown that, under some circumstances, rotation disks can be preserved during the merging process or rapidly regrown after coalescence. Our goal is to analyse in detail the ionised gas kinematics in a s le of ULIRGs to infer the incidence of gas rotational dynamics in late-stage interacting galaxies and merger remnants. Aims. We analysed integral field spectrograph MUSE data of a s le of 20 nearby ( z 0.165) ULIRGs (with 29 in idual nuclei) as part of the Physics of ULIRGs with MUSE and ALMA (PUMA) project. We used multi-Gaussian fitting techniques to identify gaseous disk motions and the 3D-Barolo tool to model them. Methods. We found that 27% (8 out of 29) in idual nuclei are associated with kiloparsec-scale disk-like gas motions. The rest of the s le displays a plethora of gas kinematics, dominated by winds and merger-induced flows, which makes the detection of rotation signatures difficult. On the other hand, the incidence of stellar disk-like motions is ∼2 times larger than gaseous disks, as the former are probably less affected by winds and streams. The eight galaxies with a gaseous disk present relatively high intrinsic gas velocity dispersion ( σ 0 ∈ [30 − 85] km s −1 ), rotationally supported motions (with gas rotation velocity over velocity dispersion v rot / σ 0 ∼ 1 − 8), and dynamical masses in the range (2 − 7)×10 10 M ⊙ . By combining our results with those of local and high- z disk galaxies (up to z ∼ 2) from the literature, we found a significant correlation between σ 0 and the offset from the main sequence ( δ MS), after correcting for their evolutionary trends. Results. Our results confirm the presence of kiloparsec-scale rotating disks in interacting galaxies and merger remnants in the PUMA s le, with an incidence going from 27% (gas) to ≲50% (stars). Their gas σ 0 is up to a factor of ∼4 higher than in local normal main sequence galaxies, similar to high- z starbursts as presented in the literature this suggests that interactions and mergers enhance the star formation rate while simultaneously increasing the velocity dispersion in the interstellar medium.
Hubble Space TelescopeHα imaging of star-forming galaxies atz≃ 1–1.5: evolution in the size and luminosity of giant H ii regions
Publisher: Oxford University Press (OUP)
Date: 02-11-2012
Monitoring of Ligand-independent Dimerization and Ligand-induced Conformational Changes of Melatonin Receptors in Living Cells by Bioluminescence Resonance Energy Transfer
Publisher: Elsevier BV
Date: 06-2002
Metabolic Regulation of the Epigenome Drives Lethal Infantile Ependymoma
Publisher: Elsevier BV
Date: 06-2020
DOI: 10.1016/J.CELL.2020.04.047
Abstract: Posterior fossa A (PFA) ependymomas are lethal malignancies of the hindbrain in infants and toddlers. Lacking highly recurrent somatic mutations, PFA ependymomas are proposed to be epigenetically driven tumors for which model systems are lacking. Here we demonstrate that PFA ependymomas are maintained under hypoxia, associated with restricted availability of specific metabolites to diminish histone methylation, and increase histone demethylation and acetylation at histone 3 lysine 27 (H3K27). PFA ependymomas initiate from a cell lineage in the first trimester of human development that resides in restricted oxygen. Unlike other ependymomas, transient exposure of PFA cells to ambient oxygen induces irreversible cellular toxicity. PFA tumors exhibit a low basal level of H3K27me3, and, paradoxically, inhibition of H3K27 methylation specifically disrupts PFA tumor growth. Targeting metabolism and/or the epigenome presents a unique opportunity for rational therapy for infants with PFA ependymoma.
JADES Initial Data Release for the Hubble Ultra Deep Field: Revealing the Faint Infrared Sky with Deep JWST NIRCam Imaging
Publisher: American Astronomical Society
Date: 27-10-2023
The Identification of Novel Protein-Protein Interactions in Liver that Affect Glucagon Receptor Activity
Publisher: Public Library of Science (PLoS)
Date: 15-06-2015
SAPCD2 Controls Spindle Orientation and Asymmetric Divisions by Negatively Regulating the Gαi-LGN-NuMA Ternary Complex
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.DEVCEL.2015.12.016
Abstract: Control of cell- ision orientation is integral to epithelial morphogenesis and asymmetric cell ision. Proper spatiotemporal localization of the evolutionarily conserved Gαi-LGN-NuMA protein complex is critical for mitotic spindle orientation, but how this is achieved remains unclear. Here we identify Suppressor APC domain containing 2 (SAPCD2) as a previously unreported LGN-interacting protein. We show that SAPCD2 is essential to instruct planar mitotic spindle orientation in both epithelial cell cultures and mouse retinal progenitor cells in vivo. Loss of SAPCD2 randomizes spindle orientation, which in turn disrupts cyst morphogenesis in three-dimensional cultures, and triples the number of terminal asymmetric cell isions in the developing retina. Mechanistically, we show that SAPCD2 negatively regulates the localization of LGN at the cell cortex, likely by competing with NuMA for its binding. These results uncover SAPCD2 as a key regulator of the ternary complex controlling spindle orientation during morphogenesis and asymmetric cell isions.
BioID-based Identification of Skp Cullin F-box (SCF)β-TrCP1/2 E3 Ligase Substrates*
Publisher: Elsevier BV
Date: 07-2015
In-orbit Performance of the Near-infrared Spectrograph NIRSpec on the James Webb Space Telescope
Publisher: IOP Publishing
Date: 03-2023
Abstract: The Near-Infrared Spectrograph (NIRSpec) is one of the four focal plane instruments on the James Webb Space Telescope. In this paper, we summarize the in-orbit performance of NIRSpec, as derived from data collected during its commissioning c aign and the first few months of nominal science operations. More specifically, we discuss the performance of some critical hardware components such as the two NIRSpec Hawaii-2RG detectors, wheel mechanisms, and the microshutter array. We also summarize the accuracy of the two target acquisition procedures used to accurately place science targets into the slit apertures, discuss the current status of the spectrophotometric and wavelength calibration of NIRSpec spectra, and provide the “as measured” sensitivity in all NIRSpec science modes. Finally, we point out a few important considerations for the preparation of NIRSpec science programs.
Outflows of hot molecular gas in ultra-luminous infrared galaxies mapped with VLT-SINFONI
Publisher: EDP Sciences
Date: 11-2017
Related Organisations
Universidad Complutense De Madrid Facultad De Ciencias Físicas
Location: Spain
Related Funding Activities
No related grants have been discovered for Stephane Angers.