ORCID Profile
0000-0003-1763-8433
Current Organisations
KU Leuven
,
University of Aveiro
,
Universidade de Aveiro
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Publisher: Rockefeller University Press
Date: 21-07-2021
DOI: 10.1084/JEM.20210571
Abstract: The ability to adapt to environmental stress, including therapeutic insult, contributes to tumor evolution and drug resistance. In suboptimal conditions, the integrated stress response (ISR) promotes survival by d ening cytosolic translation. We show that ISR-dependent survival also relies on a concomitant up-regulation of mitochondrial protein synthesis, a vulnerability that can be exploited using mitoribosome-targeting antibiotics. Accordingly, such agents sensitized to MAPK inhibition, thus preventing the development of resistance in BRAFV600E melanoma models. Additionally, this treatment compromised the growth of melanomas that exhibited elevated ISR activity and resistance to both immunotherapy and targeted therapy. In keeping with this, pharmacological inactivation of ISR, or silencing of ATF4, rescued the antitumoral response to the tetracyclines. Moreover, a melanoma patient exposed to doxycycline experienced complete and long-lasting response of a treatment-resistant lesion. Our study indicates that the repurposing of mitoribosome-targeting antibiotics offers a rational salvage strategy for targeted therapy in BRAF mutant melanoma and a therapeutic option for NRAS-driven and immunotherapy-resistant tumors.
Publisher: SAGE Publications
Date: 09-07-2016
Abstract: This article theorizes the functional relationship between the human components (i.e., scholars) and non-human components (i.e., structural configurations) of academic domains. It is organized around the following question: in what ways have scholars formed and been formed by the structural configurations of their academic domain? The article uses as a case study the academic domain of education and technology to examine this question. Its authorship approach is innovative, with a worldwide collection of academics (99 authors) collaborating to address the proposed question based on their reflections on daily social and academic practices. This collaboration followed a three-round process of contributions via email. Analysis of these scholars’ reflective accounts was carried out, and a theoretical proposition was established from this analysis. The proposition is of a mutual (yet not necessarily balanced) power (and therefore political) relationship between the human and non-human constituents of an academic realm, with the two shaping one another. One implication of this proposition is that these non-human elements exist as political ‘actors’, just like their human counterparts, having ‘agency’ – which they exercise over humans. This turns academic domains into political (functional or dysfunctional) ‘battlefields’ wherein both humans and non-humans engage in political activities and actions that form the identity of the academic domain. For more information about the authorship approach, please see Al Lily AEA (2015) A crowd-authoring project on the scholarship of educational technology. Information Development. doi: 10.1177/0266666915622044.
Publisher: Cold Spring Harbor Laboratory
Date: 13-01-2023
DOI: 10.1101/2023.01.13.521174
Abstract: Single-cell multi-omics methods are enabling the study of cell state ersity, which is largely determined by the interplay of the genome, epigenome, and transcriptome. Here, we describe Gtag& T-seq, a genome-and-transcriptome sequencing (G& T-seq) protocol of the same single cells that omits whole-genome lification (WGA) by using direct genomic tagmentation (Gtag). Gtag drastically decreases the cost and improves coverage uniformity at both the single-cell and pseudo-bulk level when compared to WGA-based G& T-seq. We also show that transcriptome-based DNA copy number inference has limited resolution and accuracy, underlining the importance of affordable multi-omic approaches. Moreover, applying Gtag& T-seq to a melanoma xenograft model before treatment and at minimal residual disease revealed differential cell state plasticity and treatment response between cancer subclones. In summary, Gtag& T-seq is a low-cost and accurate single-cell multi-omics method enabling the exploration of genetic alterations and their functional consequences in single cells at scale.
Location: No location found
No related grants have been discovered for Luís Pedro.