A5000500798- S100 Proteins and Annexins
- Amyotrophic Lateral Sclerosis Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenetic and Muscular Disorders Research
- Viral Infectious Diseases and Gene Expression in Insects
- Sepsis Diagnosis and Treatment
- Cell Image Analysis Techniques
- Genetic Neurodegenerative Diseases
- Biosimilars and Bioanalytical Methods
- Cholinesterase and Neurodegenerative Diseases
- Protein purification and stability
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Immune Response and Inflammation
- Advanced Glycation End Products research
- Neonatal Respiratory Health Research
- RNA and protein synthesis mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Computational Drug Discovery Methods
- Advanced Statistical Methods and Models
- Traumatic Brain Injury and Neurovascular Disturbances
- Prion Diseases and Protein Misfolding
AstraZeneca (United Kingdom)
2023-2024
Università Cattolica del Sacro Cuore
2017-2019
Istituto di Farmacologia Traslazionale
2015
A common feature of non-coding repeat expansion disorders is the accumulation RNA repeats as foci in nucleus and/or cytoplasm affected cells. These can be toxic by sequestering RNA-binding proteins, thus affecting various steps post-transcriptional gene regulation. However, precise step that C9orf72 GGGGCC (G4C2) expansion, major genetic cause Amyotrophic Lateral Sclerosis, still poorly defined. In this work, we set out to characterise these mechanisms identifying binding proteins....
TAR DNA-binding protein 43 (TDP-43) is an RNA-binding and a major component of aggregates found in amyotrophic lateral sclerosis several other neurodegenerative diseases. TDP-43 exists as full-length two shorter forms 25 35 kDa. Full-length mutant TDP-43s patients re-localize from the nucleus to cytoplasm part mitochondria, where they exert toxic role associated with neurodegeneration. However, induction mitochondrial damage by fragments yet be clarified. In this work, we show that kDa...
S100A4, belonging to a large multifunctional S100 protein family, is Ca2+-binding with significant role in stimulating the motility of cancer and immune cells, as well promoting pro-inflammatory properties different cell types. In CNS, there limited information concerning S100A4 presence function. this study, we analyzed expression effect transcriptional inhibitor niclosamide murine activated primary microglia. We found that was strongly up-regulated reactive microglia prevented NADPH...
Neuroinflammation is one of the major players in amyotrophic lateral sclerosis (ALS) pathogenesis, and astrocytes are significantly involved this process. The astrocytic protein S100B can be released pathological states activating receptor for advanced glycation end products (RAGE). Different indications point to an aberrant expression RAGE ALS. In work, we observed that progressively selectively upregulated diseased rats with a tissue-specific timing pattern, correlated level...
Small airway epithelial cells (SAECs) play a central role in the pathogenesis of lung diseases and are now becoming crucial cellular model for target identification validation drug discovery. However, primary cell lines such as SAECs often difficult to transfect using traditional lipofection methods; therefore, gene editing CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 is carried out through ribonucleoprotein (RNP) electroporation. Here we have established robust,...
Hit screening, which involves the identification of compounds or targets capable modulating disease-relevant processes, is an important step in drug discovery. Some assays, such as image-based high-content screenings, produce complex multivariate readouts. To fully exploit richness data, advanced analytical methods that go beyond conventional univariate approaches should be employed. In this work, we tackle problem hit assays. As with a from assay can defined candidate yields value...
Quality by Design (QbD) is an approach to assay development determine the design space, which range of variable settings that should result in satisfactory quality. Typically, QbD applied manufacturing, but it works just as well preclinical space. Through three examples, we illustrate with experimental and associated data analysis space for assays.
Wnt/β-catenin signaling plays an important role in controlling lung epithelial cell homeostasis and fate commitment is dysregulated COPD with reduced Wnt activity. As it controls alveolar self-renewal, we performed a whole genome CRISPR screen to identify negative regulators of for potential regenerative therapies addressing emphysema. 152 hits were identified A549 cells (p<0.1 vs. neutral control), which then screened small airway pathway activation by β-catenin nuclear translocation...