Alvaro Inglés-Prieto

Alvaro Inglés-Prieto
CeMM Research Center for Molecular Medicine | CeMM · Giulio Superti-Furga Lab

PhD

About

32
Publications
4,625
Reads
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1,134
Citations
Citations since 2016
15 Research Items
960 Citations
2016201720182019202020212022050100150
2016201720182019202020212022050100150
2016201720182019202020212022050100150
2016201720182019202020212022050100150
Additional affiliations
January 2008 - December 2012
University of Granada
Position
  • PhD Student

Publications

Publications (32)
Article
Zinc is the second most prevalent metal element present in living organisms, and control of its concentration is pivotal to physiology. The amount of zinc available to the cell cytoplasm is regulated by the activity of members of the SLC39 family, the ZIP proteins. Selectivity of ZIP transporters has been the focus of earlier studies which provided...
Article
Full-text available
FGFs and their high-affinity receptors (FGFRs) play key roles in development, tissue repair, and disease. Because FGFRs bind overlapping sets of ligands, their individual functions cannot be determined using ligand stimulation. Here, we generated a light-activated FGFR2 variant (OptoR2) to selectively activate signaling by the major FGFR in keratin...
Article
Full-text available
The solute carrier (SLC) superfamily represents the biggest family of transporters with important roles in health and disease. Despite being attractive and druggable targets, the majority of SLCs remains understudied. One major hurdle in research on SLCs is the lack of tools, such as cell-based assays to investigate their biological role and for dr...
Article
Full-text available
Optogenetics has been harnessed to shed new mechanistic light on current and future therapeutic strategies. This has been to date achieved by the regulation of ion flow and electrical signals in neuronal cells and neural circuits that are known to be affected by disease. In contrast, the optogenetic delivery of trophic biochemical signals, which su...
Preprint
Full-text available
Optogenetics has been harnessed to shed new mechanistic light on current therapies and to develop future treatment strategies. This has been to date achieved by the correction of electrical signals in neuronal cells and neural circuits that are affected by disease. In contrast, the optogenetic delivery of trophic biochemical signals, which support...
Article
Full-text available
The Innovative Medicines Initiative Consortium RESOLUTE has started to develop tools and produce data sets to de-orphanize transporters in the solute carrier protein (SLC) superfamily, thereby lowering the barrier for the scientific community to explore SLCs as an attractive drug target class. The Innovative Medicines Initiative Consortium RESOLUTE...
Article
Full-text available
Solute carriers (SLCs) are the largest family of transmembrane transporters in humans and are major determinants of cellular metabolism. Several SLCs have been shown to be required for the uptake of chemical compounds into cellular systems, but systematic surveys of transporter–drug relationships in human cells are currently lacking. We performed a...
Article
Full-text available
Evolution involves not only adaptation, but also the degradation of superfluous features. Many examples of degradation at the morphological level are known (vestigial organs, for instance). However, the impact of degradation on molecular evolution has been rarely addressed. Thioredoxins serve as general oxidoreductases in all cells. Here, we report...
Preprint
Full-text available
Evolution involves not only adaptation, but also the degradation of superfluous features. Many examples of degradation at the morphological level are known (vestigial organs, for instance). However, the impact of degradation on molecular evolution has been rarely addressed. Thioredoxins serve as general oxidoreductases in all cells. Here, we report...
Preprint
Full-text available
The activity and potency of a drug is inherently affected by the metabolic state of its target cell. Solute Carriers (SLCs) represent the largest family of transmembrane transporters in humans and constitute major determinants of cellular metabolism. Several SLCs have been shown to be required for the uptake of individual chemical compounds into ce...
Article
Full-text available
During metazoan development, the temporal pattern of morphogen signaling is critical for organizing cell fates in space and time. Yet, tools for temporally controlling morphogen signaling within the embryo are still scarce. Here, we developed a photoactivatable Nodal receptor to determine how the temporal pattern of Nodal signaling affects cell fat...
Article
Optogenetics and photopharmacology enable the spatio-temporal control of cell and animal behavior by light. Although red light offers deep-tissue penetration and minimal phototoxicity, very few red-light-sensitive optogenetic methods are currently available. We have now developed a red-light-induced homodimerization domain. We first showed that an...
Article
Optogenetik und Photopharmakologie erm?glichen eine lichtgesteuerte r?umliche und zeitliche Manipulation von Prozessen in Zellen und in Tiermodellen. Obwohl rotes Licht durch minimale Toxizit?t und gute Gewebedurchdringung ?berzeugt, sind nur wenige f?r rotes Licht empfindliche optogenetische Hilfsmittel bekannt. Wir haben eine neue, durch rotes Li...
Article
High-throughput live-cell screens are intricate elements of systems biology studies and drug discovery pipelines. Here, we demonstrate an optogenetics-assisted method that avoids the need for chemical activators and reporters, reduces the number of operational steps and increases information content in a cell-based small-molecule screen against hum...
Article
Full-text available
As light-based control of fundamental signaling pathways is becoming a reality, the field of optogenetics is rapidly moving beyond neuroscience. We have recently developed receptor tyrosine kinases that are activated by light and control cell proliferation, epithelial–mesenchymal transition, and angiogenic sprouting—cell behaviors central to cancer...
Article
Cultured mammalian cells are model systems in basic biology research, production platforms of proteins for medical use, and testbeds in synthetic biology. Flavin cofactors, in particular flavin mononucleotide and flavin adenine dinucleotide, are critical for cellular redox reactions and sense light in naturally-occurring photoreceptors and optogene...
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Full-text available
Local protein interactions ("molecular context" effects) dictate amino acid replacements and can be described in terms of site-specific, energetic preferences for any different amino acid. It has been recently debated whether these preferences remain approximately constant during evolution or whether, due to co-evolution of sites, they change stron...
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Receptor tyrosine kinases (RTKs) are a large family of cell surface receptors that sense growth factors and hormones and regulate a variety of cell behaviours in health and disease. Contactless activation of RTKs with spatial and temporal precision is currently not feasible. Here, we generated RTKs that are insensitive to endogenous ligands but can...
Article
Little is known about the evolution of protein structures and the degree of protein structure conservation over planetary time scales. Here, we report the X-ray crystal structures of seven laboratory resurrections of Precambrian thioredoxins dating up to approximately four billion years ago. Despite considerable sequence differences compared with e...
Article
PDI catalyzes the oxidative folding of disulfide-containing proteins. However, the sequence of reactions leading to a natively folded and oxidized protein remains unknown. Here we demonstrate a technique that enables independent measurements of disulfide formation and protein folding. We find that non-native disulfides are formed early in the foldi...
Article
Full-text available
Despite several careful experimental analyses, it is not yet clear whether protein cold-denaturation is just a "mirror image" of heat denaturation or whether it shows unique structural and energetic features. Here we report that, for a well-characterized small protein, heat denaturation and cold denaturation show dramatically different experimental...
Article
Full-text available
It is possible to travel back in time at the molecular level by reconstructing proteins from extinct organisms. Here we report the reconstruction, based on sequence predicted by phylogenetic analysis, of seven Precambrian thioredoxin enzymes (Trx) dating back between ~1.4 and ~4 billion years (Gyr). The reconstructed enzymes are up to 32 °C more st...
Article
A journey back in time is possible at the molecular level by resurrecting proteins from extinct organisms. In the last two decades several methods based on statistical theory have been developed to computationally reconstruct ancestral protein sequences. Laboratory resurrection of these ancestral proteins provides an excellent opportunity to explor...
Article
The integrin alpha6beta4 is a receptor for laminins and provides stable adhesion of epithelial cells to the basement membranes. In addition, alpha6beta4 is important for keratinocyte migration during wound healing and favours the invasion of carcinomas into surrounding tissue. The cytoplasmic domain of the beta4 subunit is responsible for most of t...

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Project (1)
Project
RESOLUTE (www.re-solute.eu) is a public-private partnership with 13 partners from academia and industry with an overarching goal: To trigger an escalation in the appreciation and intensity of research on solute carriers (SLCs) worldwide and to establish SLCs as a tractable target class for medical research and development. RESOLUTE is funded by a grant from the Innovative Medicines Initiative (IMI) and is resolved to create a decisive advancement in the overall tractability of the Solute Carrier class of protein transporters (SLCs) by providing practical and conceptual advances, and making its research output available openly and pre-competitively to the scientific community. We argue that the ~400 members of this class represent a largely untapped source of new potential drug targets and thus merit the efficiency of scale that can be achieved only through systematic and coordinated efforts. RESOLUTE's impact will transcend the funded consortium and funding period by providing the evidence for the feasibility of turning the SLC group of proteins into attractive drug targets. This will be achieved by empowering the community with reagents, research tools, protocols, and databases as well as the necessary ‘social and cultural’ instruments and exchange platforms. Thus, RESOLUTE will become an example of how a relatively understudied and biochemically demanding group of proteins can be ‘unlocked’ for research and development in a public-private partnership. Through the coupling of an inclusive, ‘open-access ethos’ to the results, techniques and reagents with the highest-possible quality of research output, RESOLUTE expects to accelerate the pace of research in the field of SLCs to the global benefit of basic academic research through to applied research in small biotech and pharmaceutical companies.