Biology subjects

Ruffinatti, F. A.

Publications and source records attributed to Ruffinatti, F. A..

6 recordsLinked to original sources

bioRxiv2025

The Pervasive Negative Regulation of Ion Channel Functional Families Across Human Cancers

The transmembrane transport of molecules and ions is fundamental to cellular homeostasis and coordination of physiological processes. During tumorigenesis, these processes undergo significant alterations in response to oncogenic transformations and microenvironmental pressures. However, a comprehensive systems-level characterization of transportome alterations across cancer types has been lacking. Here, we integrate structural, functional, and mechanistic annotations of all known human Ion Channels and Transporters (ICTs) into a curated database, organizing them into biologically coherent gene sets based on shared physiological and biophysical properties such as permeant species, gating mechanism, and transport directionality. By leveraging Gene Set Enrichment Analysis (GSEA) across transcriptomic profiles from 19 tumor types, we reveal a recurrent downregulation of ICTs--particularly ion channels--accompanied by selective upregulation of specific pump classes. Our findings uncover a conserved signature of transportome reprogramming in cancer and provide a quantitative framework for future integrative studies of ICT function. This work highlights both the complexity and plasticity of cellular transport systems in oncogenesis and offers a resource for modeling their roles in cancer systems biology.

cancer biology↗

bioRxiv2023

Profiling the Expression of Transportome Genes in cancer: A systematic approach

The transportome, the -omic layer encompassing all Ion Channels and Transporters (ICTs), is crucial for cell physiology. It is therefore reasonable to hypothesize a role of the transportome in disease, and in particular in cancer. Here, we present the Membrane Transport Protein DataBase (MTP-DB), a database collecting information on ICTs, and a pipeline that takes expression data and the MTP-DB as input to produce a broad overview of transportome dysregulation in cancer. The MTP-DB may prove useful for the study of the transportome in general, and the pipeline may be used to study the transportome in other diseases. Both tools are open source and can be found on GitHub at TCP-Lab/mtp-db and TCP-Lab/transportome_profiler, under permissive licenses. We detect that the transportome is dysregulated in cancer, and that dysregulation patterns are shared among different cancer types. It is still unclear how these patterns are linked to cancer patho-physiology.

bioinformatics↗

bioRxiv2022

BioTEA: containerized methods of analysis for microarray-based transcriptomics data

Tens of thousands of gene expression data sets describing a variety of model organisms in a many different pathophysiological conditions are currently stored in publicly available databases such as Gene Expression Omnibus (GEO) and ArrayExpress. As microarray technology is giving way to RNA-Seq, it becomes strategic to develop high-level tools of analysis to preserve access to this huge amount of information through the most sophisticated methods of data preparation and processing developed over the years, while ensuring at the same time the reproducibility of the results. To meet this need, here we present bioTEA, a novel software tool that combines the ease of use with the versatility and power of an R/Bioconductor-based differential expression analysis, starting from raw data retrieval and preparation to gene annotation. BioTEA is an R-coded pipeline, wrapped in a Python-based command line interface and containerized with Docker technology. The user can choose among multiple options--including gene filtering, batch effect handling, sample pairing, statistical test type--to adapt the algorithm flow to the structure of the particular data set. All these options are saved in single text file which can be easily shared between different laboratories to deterministically reproduce the results. In addition, a detailed log file provides accurate information about each step of analysis. Overall, these features make bioTEA an invaluable tool for both bioiformaticians and wet-lab biologists interested in transcriptomics.

bioinformatics↗

bioRxiv2022

Transcriptional landscape in BRAF wild type metastatic melanoma

Melanoma is a relative rare disease worldwide, nevertheless it has a great relevance in some countries such as in Europe. In order to shed some light upon the transcriptional profile of skin melanoma, we compared the gene expression of 6 independent tumours (all progressed towards metastatic disease and with wild type BRAF) to the expression profile of healthy melanocytes. Paraffin-embedded samples were manually microdissected to obtain enriched samples and then RNA was extracted and analysed through a microarray-based approach. An exhaustive bioinformatics analysis was performed to identify differentially expressed transcripts between the two groups as well as enriched functional terms. Overall, 50 up- and 19 down-regulated transcripts were found to be significantly changed in tumour compared to control tissue. Among the upregulated transcripts, the majority belonged to the immune response group and to proteasome, while most of the downregulated genes were related to cytosolic ribosomes. Interestingly, Gene Set Enrichment Analysis (GSEA), along with the analysis of the expression data retrieved from TCGA/GTEx databases, confirmed the general trend of downregulation affecting cytoribosome proteins. In contrast, transcripts coding for mitori-bosome proteins showed the opposite trend.

cancer biology↗

bioRxiv2020

Deletion of calcineurin from astrocytes reproduces proteome signature of Alzheimer's disease and epilepsy and predisposes to seizures

In astrocytes, calcineurin (CaN) is involved in neuroinflammation and gliosis, while its role in healthy CNS or in early neuro-pathogenesis is poorly understood. Here we report that in astroglial CaN KO (ACN-KO) mice, at one month of age, proteome is deranged in hippocampus and cerebellum. Bioinformatic analysis reveals association with Alzheimers disease (AD) and epilepsy. We found significant overlap with the proteome of an AD mouse model and of human subjects with drug-resistant epilepsy. In Barnes maze ACN-KO mice learned the task but adopted serial search strategy. Strikingly, from five months of age ACN-KO mice develop spontaneous seizures with an inflammatory signature of epileptic brains. These results suggest that astroglial CaN KO impairs hippocampal connectivity, produces proteome features of neurological disorders and predisposes mice to seizures. We suggest that astroglial CaN may serve as a novel Ca2+-sensitive switch which regulates protein expression and homeostasis in the CNS.

neuroscience↗

bioRxiv2019

Deletion of calcineurin from GFAP-expressing astrocytes impairs excitability of cerebellar and hippocampal neurons through astroglial Na+/K+ ATPase.

Astrocytes perform important housekeeping functions in the nervous system including maintenance of adequate neuronal excitability, although the regulatory mechanisms are currently poorly understood. The astrocytic Ca2+/calmodulin-activated phosphatase calcineurin (CaN) is implicated in the development of reactive gliosis and neuroinflammation, but its roles, including the control of neuronal excitability, in healthy brain is unknown. We have generated a mouse line with conditional knockout (KO) of CaN B1 (CaNB1) in glial fibrillary acidic protein (GFAP)-expressing astrocytes (astroglial calcineurin knock-out, ACN-KO). Here we report that postnatal and astrocyte-specific ablation of CaNB1 did not alter normal growth and development as well as adult neurogenesis. Yet, we found that specific deletion of astrocytic CaN selectively impairs intrinsic neuronal excitability in hippocampal CA1 pyramidal neurons and cerebellar granule cells (CGCs). This impairment was associated with a decrease in after-hyperpolarization in CGC, while passive properties were unchanged, suggesting impairment of K+ homeostasis. Indeed, blockade of Na+/K+-ATPase (NKA) with ouabain phenocopied the electrophysiological alterations observed in ACN-KO CGCs. In addition, NKA activity was significantly lower in cerebellar and hippocampal lysates and in pure astrocytic cultures from ACN-KO mice. While no changes were found in protein levels, NKA activity was inhibited by the specific CaN inhibitor FK506 in both cerebellar lysates and primary astroglia from control mice, suggesting that CaN directly modulates NKA activity and in this manner controls neuronal excitability. In summary, our data provide formal evidence for the notion that astroglia is fundamental for controlling basic neuronal functions and place CaN center-stage as an astrocytic Ca2+-sensitive switch.

neuroscience↗