A5074144174- Inflammatory Bowel Disease
- Phagocytosis and Immune Regulation
- Ferroptosis and cancer prognosis
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- MicroRNA in disease regulation
- Epigenetics and DNA Methylation
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Immune Cell Function and Interaction
- Peptidase Inhibition and Analysis
- RNA Research and Splicing
- Prostate Cancer Treatment and Research
- Circular RNAs in diseases
- Cancer-related molecular mechanisms research
- Cancer, Lipids, and Metabolism
- RNA modifications and cancer
- Congenital heart defects research
- Cancer-related gene regulation
- Metabolomics and Mass Spectrometry Studies
- Cancer Genomics and Diagnostics
- Immunotherapy and Immune Responses
- Nuclear Structure and Function
- CAR-T cell therapy research
- Adipose Tissue and Metabolism
- Neurogenetic and Muscular Disorders Research
IRCCS Humanitas Research Hospital
2019-2024
Humanitas University
2015-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2014-2022
Bioinformatics Institute
2022
Institute of Oncology Research
2010-2021
Università della Svizzera italiana
2021
SAIC-GM (China)
2020
University of Parma
2016
Inserm
2016
Université de Montpellier
2016
Inflammation is a key component of cardiac disease, with macrophages and T lymphocytes mediating essential roles in the progression to heart failure. Nonetheless, little insight exists on other immune subsets involved cardiotoxic response.Here, we used single-cell RNA sequencing map composition standard murine nonischemic, pressure-overload failure model. By focusing our analysis CD45+ cells, obtained higher resolution identification cell heart, at early late stages disease controls. We then...
Cardiac hypertrophy, initially an adaptive response of the myocardium to stress, can progress heart failure. The epigenetic signature underlying this phenomenon is poorly understood. Here, we report on genome-wide distribution seven histone modifications in adult mouse cardiomyocytes subjected a prohypertrophy stimulus vivo. We found set promoters with pattern that distinguishes specific functional classes genes regulated hypertrophy and identified 9,207 candidate active enhancers whose...
Neutrophils are a component of the tumor microenvironment and have been predominantly associated with cancer progression. Using genetic approach complemented by adoptive transfer, we found that neutrophils essential for resistance against primary 3-methylcholantrene-induced carcinogenesis. were activation an interferon-γ-dependent pathway immune resistance, polarization subset CD4- CD8- unconventional αβ T cells (UTCαβ). Bulk single-cell RNA sequencing (scRNA-seq) analyses unveiled...
microRNAs (miRNAs) modulate gene expression by repressing translation of targeted genes. Previous work has established a role for miRNAs in regulating vascular smooth muscle cell (VSMC) activity. Whether circular RNAs are involved the modulation miRNA activity VSMCs is unknown.We aimed to identify interacting with enriched and modulating cells' activity.RNA sequencing bioinformatics identified several VSMCs; however, only one, possessing multiple putative binding sites miR-145, was highly...
Tumor-associated macrophages (TAMs) are correlated with the progression of prostatic adenocarcinoma (PCa). The mechanistic basis this correlation and therapeutic strategies to target TAMs in PCa remain poorly defined. Here, single-cell RNA sequencing was used profile transcriptional landscape human PCa, leading identification a subset characterized by dysregulation pathways associated lipid metabolism. This correlates positively shorter disease-free survival is an accumulation lipids that...
Abstract Methylation at 5-cytosine (5-mC) is a fundamental epigenetic DNA modification associated recently with cardiac disease. In contrast, the role of 5-hydroxymethylcytosine (5-hmC)—5-mC’s oxidation product—in biology and disease unknown. Here we assess hydroxymethylome in embryonic, neonatal, adult hypertrophic mouse cardiomyocytes, showing that dynamic modulation hydroxymethylated specific transcriptional networks during heart development failure. hydroxymethylation marks body highly...
Background ETS transcription factors regulate important signaling pathways involved in cell differentiation and development many tissues have emerged as players prostate cancer. However, the biological impact of tumorigenesis is still debated. Methodology/Principal Findings We performed an analysis gene family using microarray data real-time PCR normal tumor along with functional studies cancer lines to understand identify key targets these factors. found frequent dysregulation genes...
It has long been known that in vitro polarized macrophages differ morphology. Stemming from a conventional immunohistology observation, we set out to test the hypothesis morphology of tumor-associated (TAMs) colorectal liver metastasis (CLM) represents correlate functional diversity with prognostic significance. Density and morphological metrics TAMs were measured correlated clinicopathological variables. While density did not survival CLM patients, cell area identified small (S-TAM) large...
Rationale : The sympathetic nervous system plays a fundamental role in the regulation of myocardial function. During chronic pressure overload, overactivation induces release catecholamines, which activate β-adrenergic receptors cardiomyocytes and lead to increased heart rate cardiac contractility. However, stimulation leads impaired function, β-blockers are widely used as therapeutic agents for treatment disease. MicroRNA-133 (miR-133) is highly expressed myocardium involved controlling...
Early prenatal inflammatory conditions are thought to be a risk factor for different neurodevelopmental disorders. Maternal interleukin-6 (IL-6) elevation during pregnancy causes abnormal behavior in offspring, but whether these defects result from altered synaptic developmental trajectories remains unclear. Here we showed that transient IL-6 via injection into pregnant mice or developing embryos enhanced glutamatergic synapses and led overall brain hyperconnectivity offspring adulthood....
Mutations in LMNA, which encodes the nuclear proteins Lamin A/C, can cause cardiomyopathy and conduction disorders. Here, we employ induced pluripotent stem cells (iPSCs) generated from human carrying heterozygous K219T mutation on LMNA to develop a disease model. Cardiomyocytes differentiated these iPSCs, thus carry K219T-LMNA, have altered action potential, reduced peak sodium current diminished velocity. Moreover, they significantly downregulated Nav1.5 channel expression increased...
The mammalian circadian clock, expressed throughout the brain and body, controls daily metabolic homeostasis. Clock function in peripheral tissues is required, but not sufficient, for this task. Because of lack specialized animal models, it unclear how tissue clocks interact with extrinsic signals to drive molecular oscillations. Here, we isolated interaction between feeding liver clock by reconstituting Bmal1 exclusively hepatocytes (Liver-RE), otherwise clock-less mice, controlling timing...
Abstract Patients with colorectal liver metastasis (CLM) present heterogenous clinical outcomes and improved classification is needed to ameliorate the therapeutic output. Macrophages (Mϕ) hold promise as prognostic classifiers targets. Here, stemming from a single-cell analysis of mononuclear phagocytes infiltrating human CLM, we identified two Mϕ markers associated distinct populations opposite relevance. The invasive margin CLM was enriched in pro-inflammatory monocyte-derived (MoMϕ)...
Adult vascular smooth muscle cells (VSMCs) dedifferentiate in response to extracellular cues such as damage and inflammation. Dedifferentiated VSMCs are proliferative, migratory, less contractile, can contribute repair well cardiovascular pathologies intimal hyperplasia/restenosis coronary artery arterial aneurysm. We here demonstrate the role of ubiquitin-like containing PHD RING finger domains 1 (UHRF1) an epigenetic master regulator VSMC plasticity. UHRF1 expression correlated with...
Inflammation contributes to the pathogenesis of heart failure, but there is limited understanding inflammation's potential benefits. Inflammatory cells secrete MYDGF (myeloid-derived growth factor) promote tissue repair after acute myocardial infarction. We hypothesized that has a role in cardiac adaptation persistent pressure overload. defined cellular sources and function wild-type (WT), Mydgf-deficient (Mydgf-/-), Mydgf bone marrow-chimeric or marrow-conditional transgenic mice with...
Background More than 50% of all patients with colorectal cancer (CRC) develop liver metastases (CLM), a clinical condition characterized by poor prognosis and lack reliable prognostic markers. Vδ1 cells are subset tissue-resident gamma delta (γδ) T lymphocytes endowed broad array antitumor functions showing natural high tropism for the liver. However, little is known about their impact in outcomes CLM. Methods We isolated human γδ from peripheral blood (PB) peritumoral (PT) tissue 93...
Abstract Aims Heart failure with reduced ejection fraction (HFrEF) is a leading cause of mortality worldwide, requiring novel therapeutic and lifestyle interventions. Metabolic alterations energy production deficit are hallmarks thereby promising targets for this complex clinical syndrome. We aim to study the molecular mechanisms effects on cardiac function in rodents HFrEF designer diet which free essential amino acids—in specifically designed percentages—substituted protein. Methods...
BACKGROUND: Metabolic distress is often associated with heart failure preserved ejection fraction (HFpEF) and represents a therapeutic challenge. Metabolism-induced systemic inflammation links comorbidities HFpEF. How metabolic changes affect myocardial in the context of HFpEF not known. METHODS: We found that ApoE knockout mice fed Western diet recapitulate many features Single-cell RNA sequencing was used for expression analysis CD45 + cardiac cells to evaluate involvement diastolic...