Francesca Pantaleoni
A5002021661- Protein Tyrosine Phosphatases
- Galectins and Cancer Biology
- RNA modifications and cancer
- Chronic Lymphocytic Leukemia Research
- Immune Cell Function and Interaction
- Cellular transport and secretion
- Immunotherapy and Immune Responses
- Peptidase Inhibition and Analysis
- PI3K/AKT/mTOR signaling in cancer
- Genetics and Neurodevelopmental Disorders
- Immunodeficiency and Autoimmune Disorders
- Bone health and treatments
- Monoclonal and Polyclonal Antibodies Research
- Lymphoma Diagnosis and Treatment
- Pancreatic function and diabetes
- Lysosomal Storage Disorders Research
- Connective tissue disorders research
- Genomic variations and chromosomal abnormalities
- T-cell and B-cell Immunology
- Genomics and Rare Diseases
- Multiple Myeloma Research and Treatments
- RNA regulation and disease
- Glycosylation and Glycoproteins Research
- Fibroblast Growth Factor Research
- Blood disorders and treatments
Bambino Gesù Children's Hospital
2017-2023
Istituti di Ricovero e Cura a Carattere Scientifico
2017-2022
Istituto Superiore di Sanità
2006-2018
Università Cattolica del Sacro Cuore
2018
Washington Center
2015
University of Washington
2015
Azienda Ospedaliero Universitaria San Giovanni Battista
2007-2011
University of Turin
2010
Noonan, LEOPARD, and cardiofaciocutaneous syndromes (NS, LS, CFCS) are developmental disorders with overlapping features including distinctive facial dysmorphia, reduced growth, cardiac defects, skeletal ectodermal anomalies, variable cognitive deficits. Dysregulated RAS-mitogen-activated protein kinase (MAPK) signal traffic has been established to represent the molecular pathogenic cause underlying these conditions. To investigate phenotypic spectrum diversity of germline mutations...
Hemophagocytic lymphohistiocytosis (HLH) is characterized by immune dysregulation due to inadequate restraint of overactivated cells and associated with a variable clinical spectrum having overlap more common pathophysiologies. HLH difficult diagnose can be part inflammatory syndromes. Here, we identify novel hematological/autoinflammatory condition (NOCARH syndrome) in four unrelated patients superimposable features, including neonatal-onset cytopenia dyshematopoiesis, autoinflammation,...
It is unknown whether zoledronic acid (ZA) at clinically relevant doses active against tumours not located in bone. Mice transgenic for the activated ErbB-2 oncogene were treated with a cumulative number of equivalent to that recommended human beings. A significant increase tumour-free and overall survival was observed mice ZA. At compatible concentrations, ZA modulated mevalonate pathway affected protein prenylation both tumour cells macrophages. marked reduction tumour-associated...
RASopathies, a family of disorders characterized by cardiac defects, defective growth, facial dysmorphism, variable cognitive deficits and predisposition to certain malignancies, are caused constitutional dysregulation RAS signalling predominantly through the RAF/MEK/ERK (MAPK) cascade. We report on two germline mutations (p.Gly39dup p.Val55Met) in RRAS, gene encoding small monomeric GTPase controlling cell adhesion, spreading migration, underlying rare (2 subjects among 504 individuals...
Noonan syndrome (NS) is among the most common nonchromosomal disorders affecting development and growth. NS caused by aberrant RAS-MAPK signaling genetically heterogeneous, which explains, in part, marked clinical variability documented for this Mendelian trait. Recently, we others identified SOS1 as a major gene underlying NS. Here, explored further spectrum of mutations their associated phenotypic features. Mutation scanning entire coding sequence allowed identification 33 different...
Aberrant activation or inhibition of potassium (K+) currents across the plasma membrane cells has been causally linked to altered neurotransmission, cardiac arrhythmias, endocrine dysfunction, and (more rarely) perturbed developmental processes. The K+ channel subfamily K member 4 (KCNK4), also known as TRAAK (TWIK-related arachidonic acid-stimulated channel), belongs mechano-gated ion channels TRAAK/TREK two-pore-domain (K2P) channels. While K2P are well contribute resting potential...
Activating mutations in v-Ha-ras Harvey rat sarcoma viral oncogene homolog (HRAS) have recently been identified as the molecular cause underlying Costello syndrome (CS). To further investigate phenotypic spectrum associated with germline HRAS and characterize their diversity, subjects a diagnosis of CS (N = 9), Noonan (NS; N 36), cardiofaciocutaneous (CFCS; 4), or phenotype suggestive these conditions but without definitive 12) were screened for entire coding sequence gene. A de novo...
Abstract Mutations in genes coding for transducers participating the RAS/MAPK pathway have been identified as molecular cause underlying a group of clinically related developmental disorders with cognitive deficits variable severity. To determine spectrum defects associated dysregulation this signal cascade, we studied profile abilities patients mutations affecting PTPN11 , SOS1 HRAS KRAS BRAF RAF1 and MEK1 phenotype–genotype correlations. Our findings support observation that heterogeneity...
Noonan syndrome (NS), the most common RASopathy, is caused by mutations affecting signaling through RAS and MAPK cascade. Recently, genome scanning has discovered novel genes implicated in NS, whose function RAS-MAPK remains obscure, suggesting existence of unrecognized circuits contributing to signal modulation this pathway. Among these genes, leucine zipper-like transcriptional regulator 1 (LZTR1) encodes a functionally poorly characterized member BTB/POZ protein superfamily. Two classes...
The RASopathies constitute a family of autosomal-dominant disorders whose major features include facial dysmorphism, cardiac defects, reduced postnatal growth, variable cognitive deficits, ectodermal and skeletal anomalies, susceptibility to certain malignancies. Noonan syndrome (NS), the commonest RASopathy, is genetically heterogeneous caused by functional dysregulation signal transducers regulatory proteins with roles in RAS/extracellular signal-regulated kinase (ERK) transduction...
The endosomal sorting complexes required for transport (ESCRTs) are essential multiple membrane modeling and membrane-independent cellular processes. Here we describe six unrelated individuals with de novo missense variants affecting the ATPase domain of VPS4A, a critical enzyme regulating ESCRT function. Probands had structural brain abnormalities, severe neurodevelopmental delay, cataracts, growth impairment, anemia. In cultured cells, overexpression VPS4A mutants caused enlarged vacuoles...
Abstract Vγ9Vδ2 T cells play a major role as effector of innate immune responses against microbes, stressed cells, and tumor cells. They constitute <5% PBLs but can be expanded by zoledronic acid (ZA)-treated monocytes or dendritic (DC). Much less is known about their ability to act cellular adjuvants bridging adaptive immunity, especially in patients with cancer. We have addressed this issue multiple myeloma (MM), prototypic disease several dysfunctions that also affect γδ DC....
Abstract Craniosynostosis, the premature fusion of one or more cranial sutures, is a developmental defect that disrupts morphogenetic program, leading to variable dysmorphic craniofacial features and associated functional abnormalities. Craniosynostosis frequently observed as an feature in number clinically genetically heterogeneous syndromic conditions, including group disorders caused by activating mutations genes coding for fibroblast growth factor receptor family members FGFR1, FGFR2,...
Germline mutations in PTPN11, the gene encoding Src-homology 2 (SH2) domain-containing protein tyrosine phosphatase (SHP2), cause Noonan syndrome (NS), a relatively common, clinically variable, multisystem disorder. Here, we report on identification of five different PTPN11 missense changes affecting residues Leu261 , Leu262 and Arg265 16 unrelated individuals with clinical diagnosis NS or features suggestive for this disorder, specifying novel disease-causing mutation cluster. Expression...