A5083283790- Hedgehog Signaling Pathway Studies
- Epigenetics and DNA Methylation
- Cerebral Palsy and Movement Disorders
- Cancer-related Molecular Pathways
- Genetics and Neurodevelopmental Disorders
- Cancer, Hypoxia, and Metabolism
- Pancreatic and Hepatic Oncology Research
- NF-κB Signaling Pathways
- Down syndrome and intellectual disability research
- Neurogenesis and neuroplasticity mechanisms
- Cancer Cells and Metastasis
- Oral and Maxillofacial Pathology
- Microtubule and mitosis dynamics
- Ocular Disorders and Treatments
- Pancreatic function and diabetes
- Family and Disability Support Research
- MicroRNA in disease regulation
- Collaborative Teaching and Inclusion
- IL-33, ST2, and ILC Pathways
- Mast cells and histamine
- Immune cells in cancer
- Infectious Encephalopathies and Encephalitis
- Education Systems and Policy
- Protein Kinase Regulation and GTPase Signaling
- Genetic and Kidney Cyst Diseases
Sapienza University of Rome
2010-2024
Zurich University of Teacher Education
2011-2024
Istituto Neurologico Mediterraneo
2023
University of Turin
2022
Istituto Giannina Gaslini
2017
Hammersmith Hospital
2011-2013
Imperial College London
2011-2013
Casa di Cura Città di Roma
2009
Medulloblastoma is the most common pediatric malignant brain tumor, arising from aberrant cerebellar precursors' development, a process mainly controlled by Hedgehog (Hh) signaling pathway. Histone deacetylase HDAC1 has been recently shown to modulate Hh signaling, deacetylating its effectors Gli1/2 and enhancing their transcriptional activity. Therefore, HDAC may represent potential therapeutic target for Hh-dependent tumors, but still little information available on physiological...
ABSTRACT Eukaryotic Translation Initiation Factor 5A (EIF5A) is a translation factor regulated by hypusination, unique posttranslational modification catalyzed deoxyhypusine synthetase (DHPS) and hydroxylase (DOHH) starting from the polyamine spermidine. Emerging data are showing that hypusinated EIF5A regulates key cellular processes such as autophagy, senescence, homeostasis, energy metabolism, plays role in cancer. However, effects of inhibition preclinical cancer models, mechanism...
Abstract The Hedgehog (Hh) pathway is essential for embryonic development and tissue homeostasis. Aberrant Hh signaling may occur in a wide range of human cancers, such as medulloblastoma, the most common brain malignancy childhood. Here, we identify endoplasmic reticulum aminopeptidase 1 (ERAP1), key regulator innate adaptive antitumor immune responses, previously unknown player pathway. We demonstrate that ERAP1 binds deubiquitylase enzyme USP47, displaces USP47-associated βTrCP,...
Highlights•Therapeutic doses of phenformin suppress Hedgehog-dependent tumor growth•Phenformin inhibits mGPD in cancer cells but does not affect complex I activity•Inhibition mimics and increases redox state/NADH content•Elevated NADH promotes Gli1/CtBP2 formation inhibition growthSummaryThe antidiabetic drug displays potent anticancer activity different tumors, its mechanism action remains elusive. Using Shh medulloblastoma as model, we show here that at clinically relevant concentrations,...
Colorectal cancer (CRC) is a leading cause of death. Chemoresistance pivotal feature cells to treatment failure and ATP-binding cassette (ABC) transporters are responsible for the efflux several molecules, including anticancer drugs. The Hedgehog-GLI (HH-GLI) pathway major signalling in CRC, however its role chemoresistance has not been fully elucidated. Here we show that HH-GLI favours resistance 5-fluorouracil Oxaliplatin CRC cells. We identified potential GLI1 binding sites promoter...
Abstract Mast cells (MCs) are multifaceted innate immune often present in the tumor microenvironment (TME). Several recent findings support their contribution to transition from chronic inflammation cancer. However, MC-derived mediators can either favor progression, inducing spread of tumor, or exert anti-tumorigenic functions, limiting growth. This apparent controversial role likely depends on plastic nature MCs that under different microenvironmental stimuli rapidly change phenotype and...
: Pharmacological Hedgehog (Hh) pathway inhibition has emerged as a valuable anticancer strategy. A number of small molecules able to block the at upstream receptor Smoothened (Smo) or downstream effector glioma-associated oncogene 1 (Gli1) been designed and developed. In recent study, we exploited high versatility natural isoflavone scaffold for targeting Hh signaling multiple levels showing that simultaneous Smo Gli1 provided synergistic stronger than single administration. This approach...
Medulloblastoma (MB) is the most common malignant brain tumor of childhood arising from deregulated cerebellar development. Sonic Hedgehog (Shh) pathway plays a critical role in development and its aberrant expression has been identified MB. Gene profiling cerebella 1- to 14-day-old mice unveiled cluster genes whose correlates with levels (HH) activity. From this cluster, we Insm1 Nhlh1/NSCL1 as novel HH targets induced by Shh treatment cultured granule cell progenitors. Nhlh1 promoter was...
In vielen Regionen ist aktuell ein Wechsel von mehrheitlich separativen zu integrativen Formen sonderpadagogischer Unterstutzung festzustellen. Oft sollen die der Umsetzung und ihre Wirkungen erforscht oder wissenschaftlich evaluiert werden. Obschon integrationsbezogenen Einstellungen wichtiger Beteiligter (vor allem Eltern, Lehr- Fachpersonen) dabei eine wesentliche Rolle spielen, fehlen bisher im Deutschen Sprachraum geeignete Instrumente deren empirischen Erfassung. Es besteht deshalb...
Cerebellar neural stem cells (NSCs) require Hedgehog-Gli (Hh-Gli) signalling for their maintenance and Nanog expression self-renewal. To identify novel molecular features of this regulatory pathway, we used next-generation sequencing technology to profile mRNA microRNA in cerebellar NSCs, before after induced differentiation (Diff-NSCs). Genes with higher transcript levels NSCs (vs. Diff-NSCs) included Foxm1, which proved be directly regulated by Gli Nanog. Foxm1 turn several microRNAs that...
Aberrant activation of the Hedgehog (Hh) pathway leads to development several tumors, including medulloblastoma (MB), most common pediatric brain malignancy. Hh inhibitors acting on GLI1, final effector signaling, offer a valuable opportunity overcome pitfalls existing therapies treat Hh-driven cancers. In this study, toxicity, delivery, biodistribution, and anticancer efficacy Glabrescione B (GlaB), selective GLI1 inhibitor, were investigated in preclinical models Hh-dependent MB. To its...
Abstract MYCN drives aggressive behavior and refractoriness to chemotherapy, in several tumors. Since inactivation clinical settings is not achievable, alternative vulnerabilities of MYCN-driven tumors need be explored identify more effective less toxic therapies. We previously demonstrated that PARP inhibitors enhance MYCN-induced replication stress promote mitotic catastrophe, counteracted by CHK1. Here, we showed CHK1 synergized induce death neuroblastoma cells primary cultures...
The International Classification of Functioning, Disability, and Health (ICF), established by the World Organization (WHO), provides a biopsychosocial framework for understanding addressing human functioning disability. This systematic review examines application ICF in educational contexts across four non-English languages: Chinese, German, Italian, Portuguese. findings reveal significant cross-cultural linguistic variations interpretation implementation, shaped each country’s...
Abstract Medulloblastoma (MB) is the most common malignant childhood brain tumor. About 30% of all MBs belong to I molecular subgroup, characterized by constitutive activation Sonic Hedgehog (Hh) pathway. The Hh pathway involved in several fundamental processes during embryogenesis and adult life its deregulation may lead cerebellar tumorigenesis. Indeed, activity must be maintained via a complex network activating repressor signals. One these signals KCASH2, belonging KCASH family protein,...
The Sonic Hedgehog (Hh) signal transduction pathway plays a critical role in many developmental processes and, when deregulated, may contribute to several cancers, including basal cell carcinoma, medulloblastoma, colorectal, prostate, and pancreatic cancer. In recent years, Hh inhibitors have been developed, mainly acting on the Smo receptor. However, drug resistance due mutations or non-canonical activation highlights need identify further mechanisms of modulation. Among these,...
Abstract The Sonic Hedgehog (SHH) pathway is crucial regulator of embryonic development and stemness. Its alteration leads to medulloblastoma (MB), the most common malignant pediatric brain tumor. SHH-MB subgroup best genetically characterized, however molecular mechanisms responsible for its pathogenesis are not fully understood therapeutic benefits still limited. Here, we show that pro-oncogenic stemness Spalt-like transcriptional factor 4 (SALL4) re-expressed in mouse models, high levels...