A5031910126- Cancer-related Molecular Pathways
- Hedgehog Signaling Pathway Studies
- Virus-based gene therapy research
- Cancer and Skin Lesions
- Wnt/β-catenin signaling in development and cancer
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Hair Growth and Disorders
- Cancer Research and Treatments
- Nonmelanoma Skin Cancer Studies
- PI3K/AKT/mTOR signaling in cancer
- Skin and Cellular Biology Research
- Molecular Biology Techniques and Applications
- Developmental Biology and Gene Regulation
- Cancer Cells and Metastasis
- Fibroblast Growth Factor Research
- Skin Protection and Aging
- Cancer-related gene regulation
- Protein Kinase Regulation and GTPase Signaling
- Thyroid Disorders and Treatments
- Protein Degradation and Inhibitors
- TGF-β signaling in diseases
- NF-κB Signaling Pathways
- Ubiquitin and proteasome pathways
University of Naples Federico II
2016-2025
Ceinge Biotecnologie Avanzate (Italy)
2014-2024
Institute of Genetics and Biophysics
2009-2018
Tecnologie Avanzate (Italy)
2014-2018
Istituti di Ricovero e Cura a Carattere Scientifico
2011-2013
SDN Istituto di Ricerca Diagnostica e Nucleare
2013
Telethon Institute Of Genetics And Medicine
2003-2008
Telethon Foundation
2004
Stazione Zoologica Anton Dohrn
1998-2001
Massachusetts General Hospital
1995-1999
Notch signaling promotes commitment of keratinocytes to differentiation and suppresses tumorigenesis. p63, a p53 family member, has been implicated in establishment the keratinocyte cell fate and/or maintenance epithelial self-renewal. Here we show that p63 expression is suppressed by Notch1 activation both mouse human through mechanism independent cycle withdrawal requiring down-modulation selected interferon-responsive genes, including IRF7 IRF3. In turn, elevated counteracts ability...
Abstract In recent months, Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread throughout the world. COVID-19 patients show mild, moderate or symptoms with latter ones requiring access to specialized intensive care. SARS-CoV-2 infections, pathogenesis and progression have not been clearly elucidated yet, thus forcing development of many complementary approaches identify candidate cellular pathways involved in progression. Host...
The mechanism of cell cycle withdrawal during terminal differentiation is poorly understood. We report here that the cyclin-dependent kinase (CDK) inhibitor p21Cip1/WAF1 induced at early times both keratinocyte and myoblast differentiation. induction accompanied by a drastic inhibition total Cdk2, as well p21Cip1/WAF1-associated CDK activities. has been implicated in p53-mediated G1 arrest apoptosis. In differentiation, Cip1/WAF1 observed even cells derived from p53-null mice. Similarly,...
p21Cip1/WAF1 was the first cyclin-dependent kinase (CDK) inhibitor to be identified, as a mediator of p53 in DNA damage-induced growth arrest, cell senescence, and direct CDK regulation. p21 may also play an important role differentiation-associated its expression is augmented many terminally differentiating cells. A general involvement growth/differentiation control tumor suppression has been questioned, mice lacking undergo normal development, harbor no gross alterations any their organs,...
The Sonic hedgehog (Shh) pathway plays a critical role in hair follicle physiology and is constitutively active basal cell carcinomas (BCCs), the most common human malignancy. Type 3 iodothyronine deiodinase (D3), thyroid hormone-inactivating enzyme, frequently expressed proliferating neoplastic cells, but its this context unknown. Here we show that Shh, through Gli2, directly induces D3 keratinocytes mouse BCCs. We demonstrate Gli-induced reduces intracellular hormone, thus resulting...
During development, multipotent progenitor cells establish tissue-specific programs of gene expression. In this paper, we show that p63 transcription factor, a master regulator epidermal morphogenesis, executes its function in part by directly regulating expression the genome organizer Satb1 cells. binds to proximal regulatory region gene, and ablation results marked reduction levels epidermis. Satb1−/− mice impaired morphology. Satb1-null epidermis, chromatin architecture differentiation...
BackgroundThe past few years have seen a vast increase in the amount of genomic data available for growing number taxa, including sets full length cDNA clones and cis-regulatory sequences. Large scale cross-species comparisons protein function sequences may help to understand emergence specific traits during evolution.Principal FindingsTo facilitate such comparisons, we developed Gateway compatible vector set, which can be used systematically dissect sequences, overexpress wild type or...
Abstract Ankyloblepharon‐ectodermal defects‐cleft lip/palate (AEC) syndrome, which is characterized by cleft palate and severe defects of the skin, an autosomal dominant disorder caused mutations in gene encoding transcription factor p63. Here, we report generation a knock‐in mouse model for AEC syndrome ( p63 +/L514F ) that recapitulates human disorder. The mutation exerts selective dominant‐negative function on wild‐type affecting progenitor cell expansion during ectodermal development...
Ankyloblepharon, ectodermal defects, cleft lip/palate (AEC) syndrome is a rare autosomal dominant disorder caused by mutations in the p63 gene, essential for embryonic development of stratified epithelia. The most severe cutaneous manifestation this long-lasting skin fragility associated with erosions after birth. Using knock-in mouse model AEC syndrome, we found that was microscopic blistering between basal and suprabasal compartments epidermis reduced desmosomal contacts. Expression...
Abstract Epithelial tumor progression often involves epithelial-mesenchymal transition (EMT). We report that increased intracellular levels of thyroid hormone (TH) promote the EMT and malignant evolution squamous cell carcinoma (SCC) cells. TH induces by transcriptionally up-regulating ZEB-1, mesenchymal genes metalloproteases suppresses E-cadherin expression. Accordingly, in human SCC, elevated D2 (the T3-producing enzyme) correlates with grade is associated an risk postsurgical relapse...
Desmoglein 1 (Dsg1) is a cadherin restricted to stratified tissues of terrestrial vertebrates, which serve as essential physical and immune barriers. Dsg1 loss-of-function mutations in humans result skin lesions multiple allergies, isolated patient keratinocytes exhibit increased proallergic cytokine expression. However, the mechanism by genetic deficiency causes chronic inflammation unknown. To determine systemic response loss, we deleted 3 tandem genes mice. Whole transcriptome analysis...
Induction of tyrosine phosphorylation is an early and specific event which required for mouse keratinocyte differentiation to occur, in response both calcium TPA (12-0-tetradecanoylphorbol-13-acetate). We report here that there increase kinase activity immunoprecipitable with anti-phosphotyrosine antibodies specifically calcium--and a number other divalent cations--within 2 min exposure. Such does not correspond any the known kinases were tested. A second induced TPA, has been identified as...
Genome-wide identification of bona-fide targets transcription factors in mammalian cells is still a challenge. We present novel integrated computational and experimental approach to identify direct factor. This consists measuring time-course (dynamic) gene expression profiles upon perturbation the factor under study, applying “reverse-engineering” algorithm (TSNI) rank genes according their probability being targets. Using primary keratinocytes as model system, we identified transcriptional...
Abstract Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate (AEC) syndrome is a rare genetic disorder caused by mutations in the TP63 gene, which encodes transcription factor essential for epidermal gene expression. A key feature of AEC chronic skin erosion, no effective treatment currently exists. Our previous studies demonstrated that associated with lead to p63 protein misfolding and aggregation, exerting dominant-negative effect. By performing high-throughput screening epigenetic...
p63, a p53 family member, is essential for the development of various stratified epithelia and one earliest markers many ectodermal structures, including epidermis, oral mucosa, apical ridge, mammary gland. Genetic regulatory mechanisms controlling p63 spatial expression during have not yet been defined. Using genomic approach, we identified an evolutionarily conserved cis-regulatory element, located 160 kb downstream first exon, which functions as keratinocyte-specific enhancer sufficient...
p63, a member of the p53 family, is essential for skin morphogenesis and epithelial stem cell maintenance. Here, we report an unexpected role TAp63 in cardiogenesis. p63 null mice exhibit severe defects embryonic cardiac development, including dilation both ventricles, defect trabeculation abnormal septation. This was accompanied by myofibrillar disarray, mitochondrial disorganization, reduction spontaneous calcium spikes. By use cells (ESCs), show that deficiency prevents expression pivotal...
Skin is the largest organ of human body and plays a key role in protecting individual from external insults. The barrier function skin performed primarily by epidermis, self-renewing stratified squamous epithelium composed cells that undergo well-characterized finely tuned process terminal differentiation. By binding to their receptors thyroid hormones (TH) regulate epidermal cell proliferation, differentiation, homeostasis. Thyroid dysfunction has multiple classical manifestations at level....
The thyroid hormone–inactivating (TH-inactivating) enzyme type 3 iodothyronine deiodinase (D3) is an oncofetal protein that rarely expressed in adult life but has been shown to be reactivated the context of proliferation and neoplasms. D3 terminates TH action within tumor microenvironment, thereby enhancing cancer cell proliferation. However, pathological role contribution metabolism have yet fully explored. Here, we describe a reciprocal regulation between cancer-associated microRNA-21...
The multilayered epidermis is established through a stratification program, which accompanied by shift from symmetric toward asymmetric divisions (ACD), process under tight control of the transcription factor p63. However, physiological signals regulating p63 activity in epidermal morphogenesis remain ill defined. Here, we reveal role for insulin/IGF-1 signaling (IIS) regulation activity. Loss IIS leads to biased loss ACD, resulting impaired stratification. Upon IIS, FoxO factors are...
The p63 gene encodes a master regulator of epidermal commitment, development, and differentiation. Heterozygous mutations in the C-terminal domain can cause ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, life-threatening disorder characterized by skin fragility severe, long-lasting erosions. Despite deep knowledge functions, little is known about mechanisms underlying disease pathology possible treatments. Here, we show that multiple AEC-associated mutations, but not...
Cleft palate is a common congenital disorder that affects up to 1 in 2500 live births and results considerable morbidity affected individuals their families. The aetiology of cleft complex with both genetic environmental factors implicated. Mutations the transcription factor p63 are one major individual causes palate; however, gene regulatory networks which functions remain only partially characterized. Our findings demonstrate as an essential molecule spatio-temporal control palatal...