Alessandra Ghigo

Alessandra Ghigo
Università degli Studi di Torino | UNITO · Dipartimento di Biotecnologie Molecolari e Scienze per la Salute

PhD

About

150
Publications
25,609
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3,931
Citations
Citations since 2017
86 Research Items
3242 Citations
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201720182019202020212022202302004006008001,000
201720182019202020212022202302004006008001,000
Introduction
Skills and Expertise
Additional affiliations
October 2014 - September 2017
Università degli Studi di Torino
Position
  • Professor (Assistant)

Publications

Publications (150)
Article
Full-text available
Cardiomyopathy deeply affects quality of life and mortality of patients with β-thalassemia or with transfusion dependent myelodysplastic syndromes. Recently, a link between Nrf2 activity and iron metabolism has been reported in liver ironoverload murine models. Here, we studied C57B6 as healthy control and Nrf2-/- male mice aged 4- and 12-months.11...
Article
Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP- and protein kinase A (PKA)-regulated channel, expressed on the luminal surface of secretory and absorptive epithelial cells. CFTR has a complex, cell-specific regulatory network playing a major role in cAMP- and Ca2+-activated secretion of electrolytes. It secretes intracellular...
Chapter
Anthracyclines (ANTs), thanks to their broad spectrum of therapeutic efficacy, represent a mainstay in the treatment of both hematological and solid tumors. However, in spite of their extensive clinical use, the major drawback of these highly potent drugs is toxicity to nontargeted tissues, which can require treatment discontinuation or the usage o...
Article
Full-text available
Doxorubicin (DOXO) remains amongst the most commonly used anti-cancer agents for the treatment of solid tumors, lymphomas, and leukemias. However, its clinical use is hampered by cardiotoxicity, characterized by heart failure and arrhythmias, which may require chemotherapy interruption, with devastating consequences on patient survival and quality...
Article
Open in new tabDownload slide In cardiomyocytes, BRCA1 can induce Circ-INSR up-regulation (upwards arrow) which in turn binds SSBP1, eventually leading to reduced mitochondrial fragmentation (‘no symbol’) and to a healthy heart. Up-regulation of Circ-INSR can thus significantly safeguard the heart against mitochondrial damage and the consequent ca...
Article
Introduction Chronic ß-AR activation is detrimental because it promotes cardiac remodeling and leads to heart failure (HF). Multiple cyclic nucleotide phosphodiesterases (PDEs) finely tune ß-AR responses by degrading and compartmentalizing cAMP. PDE2A is upregulated in HF, and PDE2A-transgenic mice are protected against catecholamine-induced arrhyt...
Article
In potentially curable cancers, long-term survival depends not only on the successful treatment of the malignancy but also on the risks associated with treatment-related toxicity, especially cardiotoxicity. Malignant lymphomas affect patients at any age, with acute and late toxicity risks that could have a severe effect on morbidity, mortality, and...
Article
Full-text available
Cystic fibrosis (CF), the most common genetic disease among the Caucasian population, is caused by mutations in the gene encoding for the CF transmembrane conductance regulator (CFTR), a chloride epithelial channel whose dysfunction results in severe airway obstruction and inflammation, eventually leading to respiratory failure. The discovery of th...
Article
Cyclic adenosine 3′,5′-monophosphate (cAMP)–elevating agents, such as β 2 -adrenergic receptor (β 2 -AR) agonists and phosphodiesterase (PDE) inhibitors, remain a mainstay in the treatment of obstructive respiratory diseases, conditions characterized by airway constriction, inflammation, and mucus hypersecretion. However, their clinical use is limi...
Article
ESCRTing lenses away from senescence ESCRT proteins control membrane fusion in various key cellular processes, but the mechanisms involved are still incompletely understood. Gulluni et al . report that ESCRT recruitment at the cytokinetic bridge is mediated by the binding of an ESCRT-II subunit to the signaling lipid phosphatidylinositol 3,4-bispho...
Article
Cardiomyopathy due to iron-overload is a severe complication of patients undergoing chronic transfusion regimen such as β-thalassemia and myelodysplastic syndromes. Previous studies have shown the key role of Nrf2, a redox-related transcriptional factor, in both β-thalassemia erythropoiesis and iron homeostasis (Matte A et al. ARS 2018, 2019; Lim P...
Article
Full-text available
Purpose of Review Doxorubicin (DOXO) is a highly effective chemotherapeutic drug employed for the treatment of a wide spectrum of cancers, spanning from solid tumours to haematopoietic malignancies. However, its clinical use is hampered by severe and dose-dependent cardiac side effects that ultimately lead to heart failure (HF). Recent Findings Mi...
Article
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Cardiovascular side effects are major shortcomings of cancer treatments causing cardiotoxicity and late-onset cardiomyopathy. While doxorubicin (Dox) has been reported as an effective chemotherapy agent, unspecific impairment in cardiomyocyte mitochondria activity has been documented. We demonstrated that the human fetal amniotic fluid-stem cell (h...
Article
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Background: TGFβ1 is a growth factor that plays a major role in the remodeling process of the heart by inducing cardiomyocyte dysfunction and apoptosis, as well as fibrosis thereby restricting heart function. TGFβ1 mediates its effect via the TGFβ receptor I (ALK5) and the activation of SMAD transcription factors, but TGFβ1 is also known as activa...
Article
Full-text available
Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel expressed on the apical membrane of epithelial cells, where it plays a pivotal role in chloride transport and overall tissue homeostasis. CFTR constitutes a unique member of the ATP-binding cassette transporter superfamily, due to its distinctive cytosolic regulatory (R)...
Article
Redox abnormalities are at the crossroad of cardiovascular diseases, cancer and cardiotoxicity from anticancer treatments. Indeed, disturbances of the redox equilibrium are common drivers of these conditions. Not only is an increase in oxidative stress a fundamental mechanism of action of anthracyclines (which have historically been the most studie...
Article
Full-text available
Phosphatidyl inositol 3 kinase gamma (PI3Kγ) is expressed in all the cell types that are involved in airway inflammation and disease, including not only leukocytes, but also structural cells, where it is expressed at very low levels under physiological conditions, while is significantly upregu-lated after stress. In the airways, PI3Kγ behaves as a...
Article
In-depth characterization of heart-brain communication in critically ill patients with severe acute respiratory failure is attracting significant interest in the COronaVIrus Disease 19 (COVID-19) pandemic era during intensive care unit (ICU) stay and after ICU or hospital discharge. Emerging research has provided new insights into pathogenic role o...
Article
Full-text available
Cystic fibrosis (CF) is an inherited disorder caused by mutations in the gene encoding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein, an ATP-gated chloride channel expressed on the apical surface of airway epithelial cells. CFTR absence/dysfunction results in defective ion transport and subsequent airway surface liquid...
Article
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Article
Full-text available
Heart failure (HF) is increasingly recognized as the major complication of chemotherapy regimens. Despite the development of modern targeted therapies such as monoclonal antibodies, doxorubicin (DOXO), one of the most cardiotoxic anticancer agents, still remains the treatment of choice for several solid and hematological tumors. The insurgence of c...
Article
Cystic fibrosis (CF) is the most common amongst rare genetic diseases, affecting more than 70.000 people worldwide. CF is characterized by a dysfunctional chloride channel, termed cystic fibrosis conductance regulator (CFTR), which leads to the production of a thick and viscous mucus layer that clogs the lungs of CF patients and traps pathogens, le...
Article
Full-text available
Cachexia is a severe complication of cancer that adversely affects the course of the disease, with currently no effective treatments. It is characterized by a progressive atrophy of skeletal muscle and adipose tissue, resulting in weight loss, a reduced quality of life, and a shortened life expectancy. Although the cachectic condition primarily aff...
Article
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Purpose of Review Along with population aging, the incidence of both heart failure (HF) and cancer is increasing. However, little is known about new-onset cancer in HF patients. This review aims at showing recent discoveries concerning this subset of patients. Recent Findings Not only cancer and HF share similar risk factors but also HF itself can...
Article
The 3′–5′-cyclic adenosine monophosphate (cAMP)/PKA pathway represents a major target for pharmacological intervention in multiple disease conditions. Although the last decade saw the concept of highly compartmentalized cAMP/PKA signaling consolidating, current means for the manipulation of this pathway still do not allow to specifically intervene...
Article
Full-text available
Background Pancreatic ductal adenocarcinoma (PDA) is the 4th leading cause of cancer mortality in developed countries, with one of the poorest prognoses among all cancers. Although 10–15% of patients are candidates for gross total surgical resection, recurrence is frequent, and the overall 5-year survival rate is around 8%. Using a proteomic approa...
Article
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Background Pathological remodeling of the myocardium has long been known to involve oxidant signaling, but so far, strategies using systemic anti-oxidants have generally failed to prevent it. Aquaporins are a family of transmembrane water channels with thirteen isoforms currently known. Some isoforms have been implicated in oxidant signaling. AQP1...
Article
Full-text available
Pathological remodeling of the myocardium has long been known to involve oxidant signaling, but strategies using systemic antioxidants have generally failed to prevent it. We sought to identify key regulators of oxidant-mediated cardiac hypertrophy amenable to targeted pharmacological therapy. Specific isoforms of the aquaporin water channels have...
Article
Anthracyclines are the cornerstone of many chemotherapy regimens for a variety of cancers. Unfortunately, their use is limited by a cumulative dose-dependent cardiotoxicity. Despite more than five decades of research, the biological mechanisms underlying anthracycline cardiotoxicity are not completely understood. In this review, we discuss the inci...
Article
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In recognition of the increasing health burden of cardiovascular disease, the Dutch CardioVascular Alliance (DCVA) was founded with the ambition to lower the cardiovascular disease burden by 25% in 2030. To achieve this, the DCVA is a platform for all stakeholders in the cardiovascular field to align policies, agendas and research. An important goa...
Article
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In the Western countries cardiovascular disease and cancer are the leading causes of death in the ageing population. Recent epidemiological data suggest that cancer is more frequent in patients with prevalent or incident cardiovascular disease, in particular heart failure. Indeed, there is a tight link in terms of shared risk factors and mechanisms...
Article
Arterial remodeling in hypertension and intimal hyperplasia involves inflammation and disrupted flow, both of which contribute to smooth muscle cell dedifferentiation and proliferation. In this context, our previous results identified phosphoinositide 3-kinase gamma (PI3Kγ) as an essential factor in inflammatory processes of the arterial wall. Here...
Article
Full-text available
Echocardiography is a reliable and reproducible method to assess non-invasively cardiac function in clinical and experimental research. Significant progress in the development of echocardiographic equipment and transducers has led to the successful translation of this methodology from humans to rodents, allowing for the scoring of disease severity...
Article
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Myocarditis can lead to autoimmune disease, dilated cardiomyopathy and heart failure, which is modelled in the mouse by cardiac myosin immunization (Experimental Autoimmune Myocarditis, EAM). STAT3 systemic inhibition exerts both preventive and therapeutic effects in EAM, and STAT3 constitutive activation elicits immune-mediated myocarditis depende...
Article
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Background: The cyclic AMP (adenosine monophosphate; cAMP)-hydrolyzing protein PDE4B (phosphodiesterase 4B) is a key negative regulator of cardiac β-adrenergic receptor stimulation. PDE4B deficiency leads to abnormal Ca2+ handling and PDE4B is decreased in pressure overload hypertrophy, suggesting that increasing PDE4B in the heart is beneficial i...
Article
Full-text available
Cardiac side effects are a major drawback of anticancer therapies, often requiring the use of low and less effective doses or even discontinuation of the drug. Among all the drugs known to cause severe cardiotoxicity are anthracyclines that, though being the oldest chemotherapeutic drugs, are still a mainstay in the treatment of solid and hematolog...
Article
Significance: The cardiac side effects of hematological treatments are a major issue of the growing population of cancer survivors, often affecting patient survival even more than the tumor for which the treatment was initially prescribed. Among the most cardiotoxic drugs are anthracyclines, highly potent anti-tumor agents, which still represent a...
Article
Cardiovascular diseases and cancer remain the leading cause of death worldwide. Despite these two conditions have long been considered as distinct clinical entities, recent epidemiological and experimental studies suggest that they should be contemplated and treated as co‐morbidities. Heart failure represents nowadays a well‐established complicatio...
Article
Cardiotoxicity is a major drawback of anticancer therapies, often hindering optimal management of cancer. Among the most cardiotoxic agents are anthracyclines (AC) that, despite being cardiotoxic, are highly effective in the treatment of a wide variety of cancers, spanning from hematological malignancies to solid tumors. Modern imaging techniques c...
Article
Full-text available
Chronic beta-AR activation is detrimental because it promotes cardiac remodeling and ultimately leads to heart failure (HF). Multiple cyclic nucleotide phosphodiesterases (PDEs) finely tune beta-AR responses by degrading and compartmentalizing cAMP. Since chronic treatment with PDE inhibitors increases mortality in HF, we postulated that decreasing...
Article
3′,5′-cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger produced in response to the stimulation of G protein-coupled receptors (GPCRs). It regulates a plethora of pathophysiological processes in different organs, including the cardiovascular system. It is now clear that cAMP is not uniformly distributed within cardiac myocytes...
Article
Full-text available
Aims Butyric acid (BUT), a short chain fatty acid produced daily by the gut microbiota, has proven beneficial in models of cardiovascular diseases. With advancements in cancer survival, an increasing number of patients are at risk of anticancer drug cardiotoxicity. Here we assess whether the novel BUT derivative phenylalanine‐butyramide (FBA) prote...
Article
Background: Cystic Fibrosis, one of the most frequent genetic diseases, is characterized by the production of viscous mucus in several organs. In the lungs, mucus clogs the airways and traps bacteria, leading to recurrent/resistant infections and lung damage. For Cystic Fibrosis patients, respiratory failure is still lethal in early adulthood sinc...
Article
Full-text available
The small-GTPase Rac1 is a key molecular regulator linking extracellular signals to actin cytoskeleton dynamics. Loss-of-function mutations in RAC1 and other genes of the Rac signaling pathway have been implicated in the pathogenesis of Intellectual Disability (ID). The Rac1 activity is negatively controlled by GAP proteins, however the effect of R...
Article
Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by irreversible chronic inflammation and airflow obstruction. It affects more than 64 million patients worldwide and it is predicted to become the third cause of death in the industrialized world by 2030. Current available therapies are not able to bloc...
Article
Full-text available
Antineoplastic drugs can be associated with several side effects, including cardiovascular toxicity (CTX). Biochemical studies have identified multiple mechanisms of CTX. Chemoterapeutic agents can alter redox homeostasis by increasing the production of reactive oxygen species (ROS) and reactive nitrogen species RNS. Cellular sources of ROS/RNS are...
Article
Full-text available
Cancer cachexia is a devastating syndrome occurring in the majority of terminally ill cancer patients. Notably, skeletal muscle atrophy is a consistent feature affecting the quality of life and prognosis. To date, limited therapeutic options are available, and research in the field is hampered by the lack of satisfactory models to study the complex...
Article
Background -Anthracyclines, such as doxorubicin (DOX), are potent anti-cancer agents for the treatment of solid tumors and hematological malignancies. However, their clinical use is hampered by cardiotoxicity. This study sought to investigate the role of PI3Kγ in DOX-induced cardiotoxicity and the potential cardio-protective and anti-cancer effects...
Article
Proper organization of the mitotic spindle is key to genetic stability, but molecular components of inter-microtubule bridges that crosslink kinetochore fibers (K-fibers) are still largely unknown. Here we identify a kinase-independent function of class II phosphoinositide 3-OH kinase α (PI3K-C2α) acting as limiting scaffold protein organizing clat...
Chapter
3′-5′-cyclic adenosine monophosphate (cAMP) and phosphatidylinositol 3,4,5 trisphosphate (PIP3) are pleiotropic second messengers generated in response to activation of G protein-coupled receptors (GPCRs) by a wide array of hormones and neurotransmitters. Although these small molecules engage distinct and seemingly unrelated downstream signal trans...
Article
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The data presented in this article are related to the research paper entitled “peroxiredoxin-2 plays a pivotal role as multimodal cytoprotector in the early phase of pulmonary hypertension” (Federti et al., 2017) [1]. Data show that the absence of peroxiredoxin-2 (Prx2) is associated with increased lung oxidation and pulmonary vascular endothelial...
Article
Pulmonary-artery-hypertension (PAH) is a life-threatening and highly invalidating chronic disorder. Chronic oxidation contributes to lung damage and disease progression. Peroxiredoxin-2 (Prx2) is a typical 2-cysteine (Cys) peroxiredoxin but its role on lung homestasis is yet to be fully defined. Here, we showed that Prx2-/- mice displayed chronic l...
Article
Receptor signaling relays on intracellular events amplified by secondary and tertiary messenger molecules. In cardiomyocytes and smooth muscle cells, cyclic AMP (cAMP) and subsequent calcium (Ca²⁺) fluxes are the best characterized receptor-regulated signaling events. However, most of receptors able to modify contractility and other intracellular r...
Article
Diabetic cardiomyopathy is a heart disease in diabetic patients, identified as ventricular dysfunction in the absence of coronary artery disease and hypertension. The molecular mechanisms underlying diabetic cardiomyopathy are still poorly understood. The protein and lipid kinase phosphoinositide 3-kinases (PI3Ks) have been suggested to regulate ca...
Article
Full-text available
Design of efficacious Treg-based therapies and establishment of clinical tolerance in autoimmune diseases have proven to be challenging. The clinical implementation of Treg immunotherapy has been hampered by various impediments related to the stability and isolation procedures of Tregs as well as the specific in vivo targets of Treg modalities. Her...
Article
Full-text available
Purpose of review: Heart Failure with preserved Ejection Fraction (HFpEF) is a prevalent disease with considerable individual and societal burden. HFpEF patients often suffer from multiple pathological conditions thatcomplicate management and adversely affect outcome, including pulmonary hypertension and chronic obstructive pulmonary disease (COPD...