Luís A Vale-Silva

Luís A Vale-Silva
Universität Heidelberg · BioQuant - Center for “Quantitative Analysis of Molecular and Cellular Biosystems”

PharmD, PhD

About

84
Publications
9,070
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
2,780
Citations
Introduction
Luís A Vale-Silva currently works at the BioQuant, University of Heidelberg. Luís currently does research in the applications of Deep Learning to Cancer Imaging Genomics.
Additional affiliations
August 2020 - present
GlaxoSmithKline
Position
  • Bioinformatician
April 2018 - July 2020
University of Heideleberg
Position
  • PostDoc Position
Description
  • Deep Learning-based Imaging Genomics systems for automated cancer diagnosis and prognosis.
May 2015 - March 2018
New York University
Position
  • PostDoc Position
Description
  • Investigating the effect of chromosome size on meiotic DNA recombination.
Education
September 2002 - June 2006
Charles University in Prague
Field of study
  • Pharmaceutical Sciences (Antifungal drug development)
September 1996 - July 2002
University of Porto
Field of study
  • Pharmaceutical Sciences

Publications

Publications (84)
Preprint
Full-text available
Chromatin-immunoprecipitation followed by sequencing (ChIP-seq) is the method of choice for mapping genome-wide binding of chromatin-associated factors. However, broadly applicable methods for between-sample comparisons are lacking. Here, we introduce SNP-ChIP, a method that leverages small-scale intra-species polymorphisms, mainly SNPs, for quanti...
Preprint
Full-text available
As part of the Synthetic Yeast 2.0 (Sc2.0) project, we designed and synthesized synthetic chromosome I. The total length of synI is ~21.4% shorter than wild-type chromosome I, the smallest chromosome in Saccharomyces cerevisiae. SynI was designed for attachment to another synthetic chromosome due to concerns of potential instability and karyotype i...
Article
Full-text available
Candida glabrata is an emerging opportunistic pathogen that is known to develop resistance to azole drugs due to increased drug efflux. The mechanism consists of CgPDR1-mediated upregulation of ATP-binding cassette transporters. A range of gain-of-function (GOF) mutations in CgPDR1 have been found to lead not only to azole resistance but also to en...
Article
Full-text available
Existing antifungal agents are still confronted to activities limited to specific fungal species and to the development of resistance. Several improvements are possible either by tackling and overcoming resistance or exacerbating the activity of existing antifungal agents. In Candida glabrata, azole resistance is almost exclusively mediated by ABC...
Article
Full-text available
The inactivation of ERG3, a gene encoding sterol Δ5,6-desaturase (essential for ergosterol biosynthesis), is a known mechanism of in vitro resistance to azole antifungal drugs in the human pathogen Candida albicans. ERG3 inactivation typically results in loss of filamentation and attenuated virulence in animal models of disseminated candidiasis. In...
Article
Full-text available
Successful meiotic recombination, and thus fertility, depends on conserved axis proteins that organize chromosomes into arrays of anchored chromatin loops and provide a protected environment for DNA exchange. Here, we show that the stereotypic chromosomal distribution of axis proteins in Saccharomyces cerevisiae is the additive result of two indepe...
Article
Full-text available
The age of precision medicine demands powerful computational techniques to handle high-dimensional patient data. We present MultiSurv, a multimodal deep learning method for long-term pan-cancer survival prediction. MultiSurv uses dedicated submodels to establish feature representations of clinical, imaging, and different high-dimensional omics data...
Preprint
Full-text available
Meiotic chromosomes organize around a cohesin-dependent axial element, which promotes meiotic recombination and fertility. In the absence of cohesin, axial-element proteins instead accumulate in poorly understood genomic regions. Here, we show in S. cerevisiae that these regions are particularly enriched for axis proteins even on wild-type chromoso...
Preprint
Full-text available
The age of precision medicine demands powerful computational techniques to handle high-dimensional patient data. We present MultiSurv, a multimodal deep learning method for long-term pan-cancer survival prediction. MultiSurv is composed of three main modules. A feature representation module includes a dedicated submodel for each input data modality...
Article
Full-text available
Human stem cell-derived hepatocyte-like cells (HLCs) offer an attractive platform to study liver biology. Despite their numerous advantages, HLCs lack critical in vivo characteristics, including cell polarity. Here, we report a stem cell differentiation protocol that uses transwell filters to generate columnar polarized HLCs with clearly defined ba...
Article
Meiotic chromosomes experience substantial strain due to morphological changes and ongoing metabolism of the DNA. Outside of meiosis, topology-modifying enzymes called topoisomerases manage this sort of strain, but their function during meiotic prophase has not been thoroughly explored... During meiotic prophase, concurrent transcription, recombina...
Preprint
Full-text available
During meiotic prophase, concurrent transcription, recombination, and changes in chromosome morphology place substantial topological strain on chromosomal DNA, but the roles of topoisomerases in this context remain poorly defined. Here, we show that meiotic Saccharomyces cerevisiae chromosomes accumulate topoisomerases primarily in promoter-contain...
Article
Full-text available
Faithful meiotic chromosome inheritance and fertility rely on the stimulation of meiotic crossover recombination by potentially genotoxic DNA double-strand breaks (DSBs). To avoid excessive damage, feedback mechanisms down-regulate DSBs, likely in response to initiation of crossover repair. In Saccharomyces cerevisiae, this regulation requires the...
Article
Full-text available
Background Chromatin-immunoprecipitation followed by sequencing (ChIP-seq) is the method of choice for mapping genome-wide binding of chromatin-associated factors. However, broadly applicable methods for between-sample comparisons are lacking. Results Here, we introduce SNP-ChIP, a method that leverages small-scale intra-species polymorphisms, mai...
Preprint
Full-text available
Faithful meiotic chromosome inheritance and fertility relies on the stimulation of meiotic crossover recombination by potentially genotoxic DNA double-strand breaks (DSBs). To avoid excessive damage, feedback mechanisms down-regulate DSBs on chromosomes that have successfully initiated crossover repair. In Saccharomyces cerevisiae , this regulation...
Article
Stem cells are highly resistant to viral infection compared to their differentiated progeny; however, the mechanism is mysterious. Here, we analyzed gene expression in mammalian stem cells and cells at various stages of differentiation. We find that, conserved across species, stem cells express a subset of genes previously classified as interferon...
Article
Full-text available
Candida glabrate is an important fungal pathogen which develops rapidly antifungal resistance in treated patients. It is known that azole treatments lead to antifungal resistance in this fungal species and that multidrug efflux transporters are involved in this process. Specific mutations in the transcriptional regulator PDR1 result in upregulation...
Preprint
Candida glabrata is an important fungal pathogen which develops rapidly antifungal resistance in treated patients. It is known that azole treatments lead to antifungal resistance in this fungal species and that multidrug efflux transporters are involved in this process. Specific mutations in the transcriptional regulator PDR1 result in upregulation...
Article
Full-text available
Candida glabrata is the second most common Candida species causing disseminated infection, after C. albicans. C. glabrata is intrinsically less susceptible to the widely used azole antifungal drugs and quickly develops secondary resistance. Resistance typically relies on drug efflux with transporters regulated by the transcription factor Pdr1. Gain...
Article
Eukaryotic transcription activators stimulate the expression of specific sets of target genes through recruitment of co-activators such as the RNA polymerase II-interacting Mediator complex. Aberrant function of transcription activators has been implicated in several diseases. However, therapeutic targeting efforts have been hampered by a lack of d...
Article
Full-text available
The objective of this study was to characterize the underlying molecular mechanisms in consecutive clinical Candida albicans isolates from a single patient displaying stepwise-acquired multidrug resistance. Nine clinical isolates (P-1 to P-9) were susceptibility tested by EUCAST EDef 7.2 and Etest. P-4, P-5, P-7, P-8 and P-9 were available for furt...
Article
Full-text available
Among existing fungal pathogens, C. glabrata is outstanding in its capacity to rapidly develop resistance to currently used antifungal agents. Resistance to the class of azoles, which are still widely used agents, varies in proportion (from 5-20%) depending on geographical area. Moreover, resistance to the class of echinocandins, which was introduc...
Article
Full-text available
Although reference broth microdilution protocol is currently available for filamentous fungi antifungal susceptibility testing (AFST), simpler alternatives as Etest(®) tend to be favoured in clinical routine, making their validation of utmost importance. In this study, Etest(®) method using 2 % glucose supplemented Muller-Hinton agar was compared t...
Article
Full-text available
Antifungal resistance of Candida species is a clinical problem in the management of diseases caused by these pathogens. In this study we identified from a collection of 423 clinical samples taken from Tunisian hospitals two clinical Candida species (Candida albicans JEY355 and Candida tropicalis JEY162) with decreased susceptibility to azoles and p...
Article
Full-text available
Three aminodi(hetero)arylamines were prepared via a palladium-catalyzed C-N Buchwald-Hartwig coupling of methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate with different bromonitrobenzenes, followed by reduction of the nitro groups of the coupling products to the corresponding amino compounds. The aminodi(hetero)arylamines thus obtained were evalua...
Article
New fluorescent methoxylated di(hetero)arylethers in the thieno[3,2-b]pyridine series were prepared by a copper-catalyzed Ullmann-type CO coupling of the methyl 3-amino-6-bromothieno[3,2-b]pyridine-2-carboxylate with ortho, meta and para-methoxyphenols, using N,N-dimethylglycine as the ligand and Cs2CO3 as the base. The compounds obtained were test...
Article
Three tricyclic compounds, a benzothieno[2,3-b]pyrrole 1, a thieno[3,2-f]indole 2 and a thieno[2,3-e]indole 3, early synthesized by us, were evaluated for their capacity to inhibit the in vitro growth of three human tumor cell lines, MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer) and SF-268 (CNS cancer) and it was found that c...
Article
Origanum vulgare subsp. virens (Hoffmanns. & Link) Bonnier & Layens and its essential oil (EO) are widely used in the treatment of respiratory and cutaneous infections in traditional medicine. In order to establish a basis for its traditional use, the antimicrobial activity of the EO of O. vulgare subsp. virens was evaluated against human fungal pa...
Article
This study evaluates the antifungal activity and mechanism of action of a new chemotype of Lavandula multifida from Portugal. The essential oil was analyzed by gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS), and the minimal inhibitory concentration (MIC) and minimal lethal concentration (MLC) of the oil and its major compo...
Article
Reference broth microdilution protocols for the antifungal susceptibility testing (AST) of yeasts are available, but routine AST relies more on simpler alternatives. In this work, the Etest and a novel flow cytometry (FC) method were compared to the Clinical Laboratory Standards Institute (CLSI) protocol M27-A3. Caspofungin and anidulafungin were t...
Article
Full-text available
ABSTRACT: A potential antitumoral fluorescent indole derivative, methyl 6-methoxy-3-(4-methoxyphenyl)-1H-indole-2-carboxylate, was evaluated for the in vitro cell growth inhibition on three human tumor cell lines, MCF-7 (breast adenocarcinoma), A375-C5 (melanoma), and NCI-H460 (non-small cell lung cancer), after a continuous exposure of 48 h, exhib...
Article
The methyl 3-amino-6-bromothieno[3,2-b]pyridine-2-carboxylate, recently reported by some of us, was reacted in Sonogashira couplings with several (hetero)arylacetylenes. The growth inhibitory activity of the novel methyl 3-amino-6-[(hetero)arylethynyl]thieno[3,2-b]pyridine-2-carboxylates obtained was evaluated on three human tumor cell lines (MCF-7...
Article
The increasing resistance of pathogenic fungi to antifungal compounds and the reduced number of available drugs led to the search for therapeutic alternatives among natural products, including xanthones. The antifungal activity of 27 simple oxygenated xanthones was evaluated by determination of their minimal inhibitory concentration on clinical and...
Article
Full-text available
In contrast with the common hematogenous dissemination of invasive aspergillosis (IA), we present case with a protracted course through anatomical planes in an immunocompromised adult male. The unusual clinical features and laboratory findings led to fungal genotyping and identification of the mold as Aspergillus viridinutans. It appears to be the...
Article
Full-text available
In the present work we report for what we believe to be the first time the antifungal activity and mechanism of action of the essential oils of Lavandula viridis from Portugal. The essential oils were isolated by hydrodistillation and analysed by GC and GC/MS. The MIC and the minimal lethal concentration (MLC) of the essential oil and its major com...
Article
Lycopersicon esculentum (tomato) fruit is a widely studied matrix. However, only few works focus their attention on its seeds, which constitute a major byproduct of the tomato processing industry. In this study the antimicrobial potential of ten different tomato seed extracts from "Bull's heart" and "Cherry" varieties were analyzed against Gram-pos...
Article
A wide variety of new bi(hetero)aryl derivatives of the thieno[3,2-b]pyridine skeleton was obtained in high to excellent yields (65-91%) by Suzuki-Miyaura cross-coupling of the methyl 3-amino-6-bromothieno[3,2-b]pyridine-2-carboxylate, recently reported by us, with aryl or heteroaryl pinacolboranes or potassium trifluoroborates. The coupling produc...
Article
Several novel 6-[(hetero)arylamino]thieno[3,2-b]pyridines were prepared by palladium-catalyzed C-N Buchwald-Hartwig coupling of the methyl 3-amino-6-bromothieno[3,2-b]pyridine-2-carboxylate with aryl and heteroarylamines, using different reaction conditions. The antitumoral activity of the di(hetero)arylamines obtained was evaluated against three r...
Article
The essential oil (EO) of Thymus x viciosoi (Pau) R. Morales was isolated and analysed by GC and GC-MS. The antifungal activity of the EO and its major components against clinically relevant yeasts and molds was then measured. Their influence on the germ tube formation in Candida albicans and the influence of the EO on the metabolic function and cy...
Article
The composition and antifungal activity of clove essential oil (EO), obtained from Syzygium aromaticum, were studied. Clove oil was obtained commercially and analysed by GC and GC-MS. The EO analysed showed a high content of eugenol (85.3 %). MICs, determined according to Clinical and Laboratory Standards Institute protocols, and minimum fungicidal...
Poster
Full-text available
Zanthoxylum tingoassuiba (Rutaceae) is a plant that has been used in traditional medicine of some Brazilian regions due to its anti-inflammatory, antifungic and antibacterial properties. The essential oil (EO) of this plant has a high amount of substances and one of them is a-bisabolol, that has well known antimicrobial properties [1]. EO are volat...
Article
For the first time, an insect-plant system, Pieris brassicae fed with Brassica rapa var. rapa, was tested for its biological capacity, namely, antioxidant (DPPH*, *NO, and O(2)*- radicals) and antimicrobial (bacteria and fungi) activities. Samples from the insect's life cycle (larvae, excrements, exuviae, and butterfly) were always found to be more...