- Cancer-related molecular mechanisms research
- Diabetes and associated disorders
- RNA Research and Splicing
- RNA modifications and cancer
- Immune cells in cancer
- Phagocytosis and Immune Regulation
- Diabetes Management and Research
- Cancer Immunotherapy and Biomarkers
- Pancreatic function and diabetes
- Adipose Tissue and Metabolism
- Cytokine Signaling Pathways and Interactions
- Immune Cell Function and Interaction
- Adipokines, Inflammation, and Metabolic Diseases
- Systemic Lupus Erythematosus Research
- RNA regulation and disease
- Circular RNAs in diseases
- NF-κB Signaling Pathways
- CAR-T cell therapy research
- Chemokine receptors and signaling
- interferon and immune responses
- Liver physiology and pathology
- Viral Infectious Diseases and Gene Expression in Insects
Vita-Salute San Raffaele University
2022-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2022-2024
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2022-2024
University of Milan
2019-2024
IRCCS Ospedale San Raffaele
2022-2024
St. Francis Medical Center
2022
Chimeric antigen receptor (CAR) T cell expansion and persistence represent key factors to achieve complete responses prevent relapses. These features are typical of early memory cells, which can be highly enriched through optimized manufacturing protocols. Here, we investigated the efficacy safety profiles CAR products generated from preselected naive/stem cells (TN/SCM), as compared with unselected (TBULK). Notwithstanding their reduced effector signature in vitro, limiting TN/SCM doses...
Antisense RNAs (asRNAs) represent an underappreciated yet crucial layer of gene expression regulation. Generally thought to modulate their sense genes in cis through sequence complementarity or act transcription, asRNAs can also regulate different molecular targets trans, the nucleus cytoplasm. Here, we performed in-depth characterization NFYC 1 (NFYC-AS1), asRNA transcribed head-to-head subunit proliferation-associated NF-Y transcription factor. Our results show that NFYC-AS1 is a...
The CCAAT box is recognized by the trimeric transcription factor NF-Y, whose NF-YA subunit present in two major splicing isoforms, NF-YAl (“long”) and NF-YAs (“short”). Little known about expression levels of NF-Y subunits tumors, nothing lung cancer. By interrogating RNA-seq TCGA GEO datasets, we found that, unlike NF-YB/NF-YC, overexpressed squamous cell carcinomas (LUSC). ratio isoforms changes from normal to cancer cells, with becoming predominant latter. increased correlates common...
The trimeric transcription factor (TF) NF-Y regulates the CCAAT box, a DNA element enriched in promoters of genes overexpressed many types cancer. regulatory NF-YA is present two major isoforms, NF-YAl ("long") and NF-YAs ("short"). There growing indication that levels are increased tumors. Here, we report interrogation RNA-Seq TCGA (The Cancer Genome Atlas)-all 576 samples-and GEO (Gene Expression Ominibus) datasets lung adenocarcinoma (LUAD). three subtypes, proliferative, inflammatory,...
NF-Y is a pioneer trimeric transcription factor formed by the Histone Fold Domain (HFD) NF-YB/NF-YC subunits and NF-YA. Three are required for DNA binding. CCAAT-specificity resides in NF-YA transactivation Q-rich domains of NF-YC. They involved alternative splicing (AS). We recently showed that overexpressed breast lung carcinomas. report here on overexpression all liver hepatocellular carcinoma (HCC) TCGA database, specifically short NF-YAs NF-YC2 (37 kDa) isoforms. This observed at tumor...
Dysglycemic obesity associates with reduced partially dysfunctional PD-1+CD4 Tconv in VAT Dysglycemia induces alterations the TCRb repertoire of CD4 cells obese prompts an increased recirculation to bloodstream accumulate liver patients dysglycemic
NF-Y is the CCAAT-binding trimer formed by histone fold domain (HFD), NF-YB/NF-YC and NF-YA. The CCAAT box generally prevalent in promoters of “cancer” genes. We reported overexpression NF-YA BRCA, LUAD LUSC, all subunits HCC. Altered splicing was found breast lung cancer. analyzed RNA-seq datasets TCGA cell lines head neck squamous carcinomas (HNSCC). partitioned data into four subtypes, deconvoluted single-cell tumors derived survival curves. enriched overexpressed “short” NF-YAs subtypes...
Abstract NF-Y is a pioneer transcription factor—TF—formed by the Histone-like NF-YB/NF-YC subunits and regulatory NF-YA. It binds to CCAAT box, an element enriched in promoters of genes overexpressed many types cancer. NF-YA present two major isoforms—NF-YAs NF-YAl—due alternative splicing, epithelial tumors. Here we analyzed expression stomach adenocarcinomas (STAD). We completed partitioning all TCGA tumor samples (450) according molecular subtypes proposed ACRG, using deep learning tool...
Aside serving as host gene for miR-205 , MIR205HG transcribes a chromatin-associated long noncoding RNA (lncRNA) able to restrain the differentiation of prostate basal cells, thus being reannotated LEADR (Long Epithelial Alu -interacting Differentiation-related RNA). We previously showed presence sequences in promoters genes modulated upon / manipulation. Notably, an element also spans first and second exons suggesting its possible involvement target selection/binding. Here, we performed...
Hepatic metastases are a poor prognostic factor of colorectal carcinoma (CRC) and new strategies to reduce the risk liver CRC colonization highly needed. Herein, we used mouse models hepatic metastatization demonstrate that continuous infusion therapeutic doses interferon-alpha (IFNα) controls invasion by acting on endothelial cells (HECs). Mechanistically, IFNα promoted development vascular antimetastatic niche characterized sinusoidal (LSECs) defenestration extracellular matrix glycocalyx...
An unbiased and replicable profiling of type 1 diabetes (T1D)-specific circulating immunome at disease onset has yet to be identified due experimental patient selection limitations. Multicolor flow cytometry was performed on whole blood from a pediatric cohort 107 patients with new-onset T1D, 85 relatives T1D 0-1 islet autoantibodies (pre-T1D_LR), 58 celiac or autoimmune thyroiditis (CD_THY) 76 healthy controls (HC). Unsupervised clustering data, validated by semi-automated gating strategy,...
Abstract Type 1 Diabetes (T1D) exhibits considerable heterogeneity, impacting prediction, prevention, diagnosis, and treatment. Precision medicine aims to tailor treatments using 'endotypes'—subtypes of disease with distinct pathophysiological mechanisms. However, proposed endotypes often lack mechanistic associations clinical outcomes, remaining elusive in T1D. This study introduces a new approach leveraging the multi-omics factor analysis (MOFA) strategy explore through data integration....
Obesity is characterized by accumulation of T cells in insulin-sensitive tissues, including the visceral adipose tissue (VAT), that can interfere with insulin signaling pathway eventually leading to resistance (IR) and type 2 diabetes. Here, we found PD-1+CD4 conventional (Tconv) cells, endowed a transcriptomic functional profile partially dysfunctional are diminished VAT obese patients dysglycemia (OB-Dys). These showed enhanced capacity recirculate into bloodstream had non-restricted TCRβ...
Abstract Hepatic metastases are a poor prognostic factor of colorectal carcinoma (CRC) and new strategies to reduce the risk liver CRC colonization highly needed. Herein, we used mouse models hepatic metastatization demonstrate that continuous infusion therapeutic doses interferon-alpha (IFNα) controls invasion by acting on endothelial cells (HECs) . Mechanistically, IFNα promoted development vascular antimetastatic niche characterized sinusoidal (LSECs) defenestration extracellular matrix...