Rosario Iemmolo

Institute for Biomedical Research and Innovation

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Sebastiano Cavallaro

National Research Council

Valentina La Cognata

Institute for Biomedical Research and Innovation

Gabriele Bonaventura

National Research Council

Maria Guarnaccia

National Research Council

Maria Luisa Barcellona

University of Catania

Lajos Okolicsànyi

Ca' Foncello Hospital

Mario Strazzabosco

Yale University

Velia D’Agata

University of Catania

G. Nassuato

University of Padua

R. Orlando

Hartford Financial Services (United States)

Cooperative Institutions

University of Catania

National Research Council

University of Padua

National Academies of Sciences, Engineering, and Medicine

Azienda Ospedaliero-Universitaria Policlinico - Vittorio Emanuele

Institute of Neurological Sciences

Policlinico Universitario di Catania

Institute for Biomedical Research and Innovation

Istituti di Ricovero e Cura a Carattere Scientifico

Institute of Cell Biology and Neurobiology

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Pathophysiology of the biliary epithelium

Mario Strazzabosco Carlo Spirlı̀Ákos Zsembery Anna Granato Luca Fabris

Pathophysiology

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Citations (7)

Effect of silybin on biliary lipid composition in rats

Pharmacological Research Communications (1983)

G. Nassuato Rosario Iemmolo Flavio Lirussi R. Orlando L Giacon

Sodium Cholate

Excretory system

10.1016/s0031-6989(83)80043-5

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Citations (7)

Miniaturized Real-Time PCR on a Q3 System for Rapid KRAS Genotyping

Sensors (2017)

Maria Guarnaccia Rosario Iemmolo Salvatore Petralia Sabrina Conoci Sebastiano Cavallaro

Colorectal cancer (CRC) is an aggressive human malignancy with a complex genomic landscape harboring KRAS mutations. In 40%-60% of patients with CRC, constantly active KRAS proteins affect the prognosis, surgical strategy, and clinical benefit from therapy with anti-epidermal growth factor receptor (EGFR) agents. For this reason, there is a greater demand for minimally-invasive diagnostic devices to characterize the genetic pattern and prevent the acquired mechanism to drug resistance. The rapid developments in cutting-edge diagnostic techniques are expected to play a growing role in medicine and represent an attractive promise to identify potential responders to personalized medicine. Here we propose a new method to simultaneously detect the main KRAS mutations on the portable real-time PCR Q3 platform. This platform is based on hybrid silicon-plastic technology implemented in a miniaturized chip able to achieve a sample-in answer-out rapid analysis, allowing a new approach to genetic counseling and testing.

Personalized Medicine

Companion diagnostic

Molecular diagnostics

10.3390/s17040831

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Case report: unpredictable outcome of portal hypertension secondary to hepatosplenic schistosomiasis in a young Brazilian woman.

Pedro Guimarães Costa B. Morandini Giorgio Perboni Donatella Tomasoni Alfredo Scalzini

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Genotyping of KRAS Mutational Status by the In-Check Lab-on-Chip Platform

Sensors (2018)

Maria Guarnaccia Rosario Iemmolo Floriana San Biagio Enrico Alessi Sebastiano Cavallaro

The KRAS oncogene is involved in the pathogenesis of several types of cancer, particularly colorectal cancer (CRC). The most frequent mutations in this gene are associated with poor survival, increased tumor aggressiveness and resistance to therapy with anti-epidermal growth factor receptor (EGFR) antibodies. For this reason, KRAS mutation testing has become increasingly common in clinical practice for personalized cancer treatments of CRC patients. Detection methods for KRAS mutations are currently expensive, laborious, time-consuming and often lack of diagnostic sensitivity and specificity. In this study, we describe the development of a Lab-on-Chip assay for genotyping of KRAS mutational status. This assay, based on the In-Check platform, integrates microfluidic handling, a multiplex polymerase chain reaction (PCR) and a low-density microarray. This integrated sample-to-result system enables the detection of KRAS point mutations, including those occurring in codons 12 and 13 of exon 2, 59 and 61 of exon 3, 117 and 146 of exon 4. Thanks to its miniaturization, automation, rapid analysis, minimal risk of sample contamination, increased accuracy and reproducibility of results, this Lab-on-Chip platform may offer immediate opportunities to simplify KRAS genotyping into clinical routine.

Multiplex

10.3390/s18010131

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CXCR2 increases in ALS cortical neurons and its inhibition prevents motor neuron degeneration in vitro and improves neuromuscular function in SOD1G93A mice

Neurobiology of Disease (2021)

Valentina La Cognata Elisabetta Golini Rosario Iemmolo Sara Balletta Giovanna Morello

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease characterized by depletion of motor neurons (MNs), for which effective medical treatments are still required. Previous transcriptomic analysis revealed the up-regulation of C-X-C motif chemokine receptor 2 (CXCR2)-mRNA in a subset of sporadic ALS patients and SOD1G93A mice. Here, we confirmed the increase of CXCR2 in human ALS cortex, and showed that CXCR2 is mainly localized in cell bodies and axons of cortical neurons. We also investigated the effects of reparixin, an allosteric inhibitor of CXCR2, in degenerating human iPSC-derived MNs and SOD1G93A mice. In vitro, reparixin rescued MNs from apoptotic cell death, preserving neuronal morphology, mitochondrial membrane potential and cytoplasmic membrane integrity, whereas in vivo it improved neuromuscular function of SOD1G93A mice. Altogether, these data suggest a role for CXCR2 in ALS pathology and support its pharmacological inhibition as a candidate therapeutic strategy against ALS at least in a specific subgroup of patients.

CXC chemokine receptors

Riluzole

10.1016/j.nbd.2021.105538

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iPSCs: A Preclinical Drug Research Tool for Neurological Disorders

International Journal of Molecular Sciences (2021)

Gabriele Bonaventura Rosario Iemmolo Giuseppe Antonino Attaguile Valentina La Cognata Brigida Sabrina Pistone

The development and commercialization of new drugs is an articulated, lengthy, and very expensive process that proceeds through several steps, starting from target identification, screening new leading compounds for testing in preclinical studies, and subsequently in clinical trials to reach the final approval for therapeutic use. Preclinical studies are usually performed using both cell cultures and animal models, although they do not completely resume the complexity of human diseases, in particular neurodegenerative conditions. To this regard, stem cells represent a powerful tool in all steps of drug discovery. The recent advancement in induced Pluripotent Stem Cells (iPSCs) technology has opened the possibility to obtain patient-specific disease models for drug screening and development. Here, we report the use of iPSCs as a disease model for drug development in the contest of neurological disorders, including Alzheimer’s (AD) and Parkinson’s disease (PD), Amyotrophic lateral Sclerosis (ALS), and Fragile X syndrome (FRAX).

Drug Development

10.3390/ijms22094596

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Citations (27)

Effect of a Bone Marrow-Derived Extracellular Matrix on Cell Adhesion and Neural Induction of Dental Pulp Stem Cells

Frontiers in Cell and Developmental Biology (2020)

Samuele Laudani Valentina La Cognata Rosario Iemmolo Gabriele Bonaventura Giusy Villaggio

Extracellular matrix (ECM) represents an essential component of the cellular niche. In this conditioned microenvironment, proliferation rate and differentiation states of stem cells are regulated by several factors. On the contrary, in in vitro experimental models, cell growth or induction procedures towards specific cell lines usually occur in contact with plastic, glass or biogel supports. In this study, we evaluated the effect of a decellularized ECM, derived by bone marrow stem cells, on neuronal differentiation of mesenchymal stem cells extracted from dental pulp (Dental Pulp Stem Cells - DPSCs). Since DPSCs derive from neuroectodermal embryonic precursors, they are thought to have a major propensity towards the neuronal differentiation than mesenchymal stem cells isolated from other sources. We hypothesized that the presence of a decellularized ECM scaffold could act positively on neuronal-DPSCs differentiation through reproduction of an in vivo-like microenvironment. Results from scanning electron microscopy, immunofluorescence and gene expression assays showed that ECM is able to positively influence the morphology of cells, their distribution and the expression of specific neuronal markers (i.e. NF-L, NF-M, NF-H, PAX6, MAP2).

Decellularization

10.3389/fcell.2020.00100

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Citations (27)

Increasing the Coding Potential of Genomes Through Alternative Splicing: The Case of PARK2 Gene

Current Genomics (2014)

Valentina La Cognata Rosario Iemmolo Velia D’Agata Soraya Scuderi Filippo Drago

The completion of the Human Genome Project aroused renewed interest in alternative splicing, an efficient and widespread mechanism that generates multiple protein isoforms from individual genes. Although our knowledge about alternative splicing is growing exponentially, its real impact on cellular life is still to be clarified. Connecting all splicing features (genes, splice transcripts, isoforms, and relative functions) may be useful to resolve this tangle. Herein, we will start from the case of a single gene, Parkinson protein 2, E3 ubiquitin protein ligase (PARK2), one of the largest in our genome. This gene is implicated in the pathogenesis of autosomal recessive juvenile Parkinsonism and it has been recently linked to cancer, leprosy, autism, type 2 diabetes mellitus and Alzheimer's disease. PARK2 primary transcript undergoes an extensive alternative splicing, which enhances transcriptomic diversification and protein diversity in tissues and cells. This review will provide an update of all human PARK2 alternative splice transcripts and isoforms presently known, and correlate them to those in rat and mouse, two common animal models for studying human disease genes. Alternative splicing relies upon a complex process that could be easily altered by both cis and trans-acting mutations. Although the contribution of PARK2 splicing in human disease remains to be fully explored, some evidences show disruption of this versatile form of genetic regulation may have pathological consequences.

10.2174/1389202915666140426003342

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Citations (35)

Combined liver and islet transplantation: about one case

Transplant International (1997)

Roberto Merenda Giorgio Enrico Gerunda Daniele Neri G. Della Giacoma Rosario Iemmolo

General hospital

10.1007/s001470050034

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Citations (1)