A5102810649- Bioinformatics and Genomic Networks
- Gene expression and cancer classification
- Gene Regulatory Network Analysis
- Computational Drug Discovery Methods
- Cell Image Analysis Techniques
- Animal testing and alternatives
- Metabolomics and Mass Spectrometry Studies
- Genomics and Phylogenetic Studies
- Gut microbiota and health
- Advanced Biosensing Techniques and Applications
- Inhalation and Respiratory Drug Delivery
- Air Quality and Health Impacts
- Cystic Fibrosis Research Advances
- RNA and protein synthesis mechanisms
- Genetics, Bioinformatics, and Biomedical Research
- Health, Environment, Cognitive Aging
- MicroRNA in disease regulation
- RNA Research and Splicing
- Advanced Proteomics Techniques and Applications
- Molecular Biology Techniques and Applications
- Statistical and Computational Modeling
- Carcinogens and Genotoxicity Assessment
- Integrated Energy Systems Optimization
- Extracellular vesicles in disease
- Protein Degradation and Inhibitors
Philip Morris International (Switzerland)
2012-2022
Telethon Institute Of Genetics And Medicine
2009-2017
Philip Morris International (United States)
2013-2016
University of Naples Federico II
2007-2016
National Technical University of Athens
2014
Veterinarians Without Borders
2012
University of Salerno
2011
Institute for Complex Systems
2011
The Open University
2010-2011
A bottleneck in drug discovery is the identification of molecular targets a compound (mode action, MoA) and its off-target effects. Previous approaches to elucidate MoA include analysis chemical structures, transcriptional responses following treatment, text mining. Methods based on require least amount information can be quickly applied new compounds. Available methods are inefficient not able support network pharmacology. We developed an automatic robust approach that exploits similarity...
MicroRNAs (miRNAs) and transcription factors control eukaryotic cell proliferation, differentiation, metabolism through their specific gene regulatory networks. However, differently from factors, our understanding of the processes regulated by miRNAs is currently limited. Here, we introduce network analysis as a new means for gaining insight into miRNA biology. A systematic all human based on Co-expression Meta-analysis Targets (CoMeTa) assigns high-resolution biological functions to...
Organotypic culture of human primary bronchial epithelial cells is a useful in vitro system to study normal biological processes and lung disease mechanisms, develop new therapies, assess the perturbations induced by environmental pollutants. Herein, we investigate whether cigarette smoke (CS) observed epithelium smokers' airways are reproducible this (AIR-100 tissue), which has been shown recapitulate most characteristics epithelium. Human AIR-100 tissues were exposed mainstream CS for 7,...
We collected a massive and heterogeneous dataset of 20 255 gene expression profiles (GEPs) from variety human samples experimental conditions, as well 8895 GEPs mouse samples. developed mutual information (MI) reverse-engineering approach to quantify the extent which mRNA levels two genes are related each other across dataset. The resulting networks consist 4 817 629 connections among transcripts in 14 461 095 45 101 mouse, with inter-species conservation 12%. inferred were compared against...
Motivation: Inferring how humans respond to external cues such as drugs, chemicals, viruses or hormones is an essential question in biomedicine. Very often, however, this cannot be addressed because it not possible perform experiments humans. A reasonable alternative consists of generating responses animal models and ‘translating’ those results The limitations translation, are far from clear, systematic assessments its actual potential urgently needed. sbv IMPROVER (systems biology...
Exposure to biologically active substances such as therapeutic drugs or environmental toxicants can impact biological systems at various levels, affecting individual molecules, signaling pathways, and overall cellular processes. The ability derive mechanistic insights from the resulting system responses requires integration of experimental measures with a priori knowledge about interacting molecules therein. We developed novel biology-based methodology that leverages network models...
The connection between chromatin nuclear organization and gene activity is vividly illustrated by the observation that transcriptional coregulation of certain genes appears to be directly influenced their spatial proximity. This fact poses more general question whether it at all feasible numerous are coregulated on a given chromosome, especially those large genomic distances, might become proximate inside nucleus. problem studied here using steered molecular dynamics simulations in order...
The biological responses to external cues such as drugs, chemicals, viruses and hormones, is an essential question in biomedicine the field of toxicology, cannot be easily studied humans. Thus, biomedical research has continuously relied on animal models for studying impact these compounds attempted 'translate' results In this context, SBV IMPROVER (Systems Biology Verification Industrial Methodology PROcess VErification Research) collaborative initiative, which uses crowd-sourcing...
The analysis of human microbiome is an exciting and rapidly expanding field research. In the past decade, biological relevance for health has become evident. Microbiome comprises a complex collection microorganisms, with their genes metabolites, colonizing different body niches. It now well known that interacts its host, assisting in bioconversion nutrients detoxification, supporting immunity, protecting against pathogenic microbes, maintaining health. Remarkable new findings showed our not...
Protein synthesis is traditionally associated with specific cytoplasmic compartments. We now show that OFD1, a centrosomal/basal body protein, interacts components of the Preinitiation complex translation (PIC) and eukaryotic Initiation Factor (eIF)4F modulates mRNA targets in kidney. demonstrate OFD1 cooperates binding protein Bicc1 to functionally control machinery at centrosome where also PIC eIF4F were shown localize mammalian cells. Interestingly, Ofd1 are both involved renal...
We previously proposed a systems toxicology framework for in vitro assessment of e-liquids. The starts with the first layer aimed at screening potential toxicity e-liquids, followed by second investigating toxicity-related mechanism and finally, third evaluating corresponding aerosols. In this work, we applied to assess impact e-liquid MESH Classic Tobacco its aerosol compared that cigarette smoke (CS) from 3R4F reference cigarette. layer, evaluated cytotoxicity profile (containing...
Dysferlin (DYSF) is a type II transmembrane protein implicated in surface membrane repair of muscle. Mutations dysferlin lead to Limb Girdle Muscular Dystrophy 2B (LGMD2B), Miyoshi Myopathy (MM), and Distal with Anterior Tibialis onset (DMAT). The DYSF complex not well understood, only few protein-binding partners have been identified thus far. To increase the set interacting for we recovered list predicted through systems biology approach. predictions are part "reverse-engineered"...
The reverse engineering of gene regulatory networks using expression profile data has become crucial to gain novel biological knowledge. Large amounts that need be analyzed are currently being produced due advances in microarray technologies. Using current algorithms analyze large sets can very computational-intensive. These emerging computational requirements met parallel computing techniques. It been shown the Network Identification by multiple Regression (NIR) algorithm performs better...
Cystic fibrosis (CF) is caused by mutations in CF transmembrane conductance regulator (CFTR). The most frequent mutation (F508del-CFTR) results altered proteostasis, that is, the misfolding and intracellular degradation of protein. F508del-CFTR proteostasis machinery its homeostatic regulation are well studied, while question whether ‘classical’ signalling pathways phosphorylation cascades might control remains barely explored. Here, we have unravelled acting selectively on...
The liver is one of the most important organs involved in elimination xenobiotic and potentially toxic substances. Cigarette smoke (CS) contains more than 7000 chemicals, including those that exert biological effects cause smoking-related diseases. Though CS not directly hepatotoxic, a growing body evidence suggests it may exacerbate pre-existing chronic disease. In this study, we integrated toxicological endpoints with molecular measurements computational analyses to investigate exposures...
The development of reduced-risk products aims to provide alternatives cigarettes that present less risk harm for adult smokers. Responsible use flavoring substances in these may fulfill an important role product acceptance. While most used such are also by the food industry and considered safe when ingested, their impact inhaled require further assessment. To aid assessment, a three-step approach combining real-time cellular analysis, phenotypic high-content screening assays, gene expression...
Transcriptomic approaches can give insight into molecular mechanisms underlying chemical toxicity and are increasingly being used as part of toxicological assessments. To aid the interpretation transcriptomic data, we have developed a systems toxicology method that relies on computable biological network model. We created first model describing cardiotoxicity in zebrafish larvae—a valuable emerging species testing associated with drugs chemicals. The is based scientific literature represents...
High-throughput omics technologies such as microarrays and next-generation sequencing (NGS) have become indispensable tools in biological research. Computational analysis interpretation of data can pose significant challenges due to a number factors, particular the systems integration required fully exploit compare from different studies and/or technology platforms. In transcriptomics, identification differentially expressed genes when studying effect(s) or contrast(s) interest constitutes...
<ns4:p>The US FDA defines modified risk tobacco products (MRTPs) as that aim to reduce harm or the of tobacco-related disease associated with commercially marketed products. Establishing a product’s potential an MRTP requires scientific substantiation including toxicity studies and measures relative those cigarette smoking. Best practices encourage verification data from such through sharing open standards. Building on experience gained OpenTox project, proof-of-concept database website...
Cigarette smoking entails chronic exposure to a mixture of harmful chemicals that trigger molecular changes over time, and is known increase the risk developing diseases. Risk assessment in context 21st century toxicology relies on elucidation mechanisms toxicity identification response markers, usually from high-throughput data, using advanced computational methodologies. The sbv IMPROVER Systems Toxicology challenge (Fall 2015-Spring 2016) aimed evaluate whether robust sparse (≤40 genes)...
Systems toxicology intends to quantify the effect of toxic molecules in biological systems and unravel their mechanisms toxicity. The development advanced computational methods is required for analyzing integrating high throughput data generated this purpose as well extrapolating predictive toxicological outcomes risk estimates. To ensure performance reliability verify conclusions from analysis, it important conduct unbiased evaluations by independent third parties. As a case study, we...