A5087975070- Epigenetics and DNA Methylation
- Genetic factors in colorectal cancer
- Cancer-related gene regulation
- FOXO transcription factor regulation
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Colorectal Cancer Treatments and Studies
- PARP inhibition in cancer therapy
- DNA Repair Mechanisms
- Peptidase Inhibition and Analysis
- Histone Deacetylase Inhibitors Research
- Genetics, Aging, and Longevity in Model Organisms
- Cancer-related Molecular Pathways
- Liver Disease Diagnosis and Treatment
- Cancer Mechanisms and Therapy
- MicroRNA in disease regulation
- Melanoma and MAPK Pathways
- CRISPR and Genetic Engineering
- Wnt/β-catenin signaling in development and cancer
- Pancreatic and Hepatic Oncology Research
- RNA Research and Splicing
- Metabolism, Diabetes, and Cancer
- Colorectal Cancer Screening and Detection
- Genomics, phytochemicals, and oxidative stress
Gastroenterology Hospital "Saverio de Bellis"
2018-2025
Medical Genetics Center
2020
University of Bari Aldo Moro
2015-2019
Cancer Research UK Manchester Institute
2018
University of Manchester
2018
Mario Negri Sud Foundation
2013
An altered metabolism is involved in the development of clear cell -renal carcinoma (ccRCC), and this tumor many genes play a fundamental role controlling metabolic activities.We delineated large-scale metabolomic profile human ccRCC, integrated it with transcriptomic data to connect variations cancer gene expression changes.Moreover, better analyze specific contribution alterations potentially associated tumorigenesis progression, we evaluated transcription primary renal cells.Untargeted...
SMYD3 is a histone lysine methyltransferase that plays an important role in transcriptional activation as member of RNA polymerase complex, and its oncogenic has been described different cancer types. We studied the expression activity preclinical model colorectal (CRC) found it strongly upregulated throughout tumorigenesis both at mRNA protein level. Our results also showed RNAi‐mediated ablation impairs CRC cell proliferation indicating required for proper growth. These data, together with...
Postzygotic mutations of the PIK3CA [phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha] gene constitutively activate PI3K/AKT/mTOR pathway in PIK3CA-related overgrowth spectrum (PROS) patients, causing congenital mosaic tissue that even multiple surgeries cannot solve. mTOR inhibitors are empirically tested and given for compassionate use these patients. PROS patients could be ideal candidates enrolment trials with PI3K/AKT inhibitors, considering "clean" cellular...
The HSF and FOXO families of transcription factors play evolutionarily conserved roles in stress resistance lifespan. In humans, the rs2802292 G-allele at FOXO3 locus has been associated with longevity all human populations tested; moreover, its copy number correlated reduced frequency age-related diseases centenarians. At molecular level, intronic increased expression FOXO3, suggesting that intron 2 may represent a regulatory region. Here we show 90-bp sequence around single nucleotide...
Abstract While aberrant cancer cell growth is frequently associated with altered biochemical metabolism, normal mitochondrial functions are usually preserved and necessary for full malignant transformation. The transcription factor FoxO3A a key determinant of homeostasis, playing dual role in survival/death response to metabolic stress therapeutics. We recently described novel arm the AMPK-FoxO3A axis cells upon nutrient shortage. Here, we show that metabolically stressed cells, recruited...
Juvenile polyposis syndrome (JPS) is an inherited autosomal dominant condition that predisposes to the development of juvenile polyps throughout gastrointestinal (GI) tract, and it poses increased risk GI malignancy. Germline causative variants were identified in
Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a cluster of conditions characterized by accumulations fat, metabolic factors such as obesity, diabetes and high cholesterol. MASLD now the leading cause chronic liver disease worldwide, with rapidly increasing trend. We aimed to demonstrate that genetic variants rs2802292 SNP can influence development even after many years. Methods: studied 650 participants from NUTRIHEP cohort, both at baseline (2005–2006)...
Intrahepatic Cholangiocarcinoma (iCCA) is characterized by a strong stromal reaction playing role in tumor progression. Thymus cell antigen 1 (THY1), also called Cluster of Differentiation 90 (CD90), key regulator cell-cell and cell-matrix interaction. In iCCA, CD90 has been reported to be associated with poor prognosis. an iCCA PDX model, we recently found that was downregulated mice treated the Notch γ-secretase inhibitor Crenigacestat. The study aims investigate relation NOTCH...
SMYD3 is frequently overexpressed in a wide variety of cancers. Indeed, its inactivation reduces tumor growth preclinical vivo animal models. However, extensive characterization vitro failed to clarify function cancer cells, although confirming importance carcinogenesis. Taking advantage mutant variant identified high-risk breast family, here we show that phosphorylation by ATM enables the formation multiprotein complex including ATM, SMYD3, CHK2, and BRCA2, which required for final loading...
Lynch syndrome (LS) is an inherited cancer susceptibility caused by germline mutations in a DNA mismatch repair (MMR) gene or the EPCAM gene. LS associated with increased lifetime risk of colorectal (CRC) and other malignancies. The screening algorithm for patient selection based on identification CRC specimens that have MMR loss/high microsatellite instability (MSI-H) are wild-type BRAFV600. Here, we sought to clinically molecularly characterize patients these features. From 2017 2023, 841...
Cells respond to DNA damage by activating a complex array of signaling networks, which include the AMPK and mTOR pathways. After double-strand breakage, ATM, core component repair system, activates AMPK-TSC2 pathway, leading inhibition cascade. Recently, we showed that both interact with SMYD3, methyltransferase involved in response. In this study, through extensive molecular characterization gastrointestinal breast cancer cells, found SMYD3 is part multiprotein response also comprises mTOR....
Abstract The prognosis of locally advanced colorectal cancer (CRC) is currently unsatisfactory. This mainly due to drug resistance, recurrence, and subsequent metastatic dissemination, which are sustained by the stem cell (CSC) population. main driver CSC gene expression program Wnt signaling, previous reports indicate that Wnt3a can activate p38 MAPK. Besides, was shown feed into canonical Wnt/β-catenin pathway. Here we show patient-derived CRC cells (CRC-SCs) characterized increased p38α...
Germline mutations of the APC gene, which encodes a multidomain protein 2843 amino acid residues, cause familial adenomatous polyposis (FAP). Three FAP clinical variants are correlated with location mutations: (1) classic profuse (>1000 adenomas), associated from codon 1250 to 1424; (2) attenuated (<100 at extremities (before 157 and after 1595); (3) intermediate colonic (100–1000 located in remaining part . In an effort decipher phenotype C-terminal germline truncating patients FAP,...
SMYD3 overexpression in several human cancers highlights its crucial role carcinogenesis. Nonetheless, specific activity cancer development and progression is currently under debate. Taking advantage of a library rare tripeptides, which we first tested for their vitro binding affinity to then used as silico probes, recently identified BRCA2, ATM, CHK2 direct interactors. To gain insight into novel cancer-related roles, here performed comprehensive analysis cluster all potential...
c-MYC is one of the most important factors involved in colorectal cancer (CRC) initiation and progression; indeed, it found to be upregulated up 80% sporadic cases. During carcinogenesis, maintained through β-catenin-mediated transcriptional activation ERK-mediated post-translational stabilization. Our data demonstrate that p38α, a kinase CRC metabolism survival, contributes c-Myc protein stability. Moreover, we show like ERK, stabilizes levels by preventing its ubiquitination. Of note, p38α...
SMYD3 is a multifunctional epigenetic enzyme with lysine methyltransferase activity and various interaction partners. It implicated in the pathophysiology of cancers but an unclear mechanism. To discover tool compounds for clarifying its biochemistry potential as therapeutic target, set drug-like was screened biosensor-based competition assay. Diperodon identified allosteric ligand; R S enantiomers were isolated, their affinities to determined (K