A5088602177- Hypothalamic control of reproductive hormones
- Growth Hormone and Insulin-like Growth Factors
- Axon Guidance and Neuronal Signaling
- Genomics and Chromatin Dynamics
- Acute Lymphoblastic Leukemia research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Genetics and Neurodevelopmental Disorders
- Autism Spectrum Disorder Research
- Chronic Myeloid Leukemia Treatments
- Congenital heart defects research
- Chromatin Remodeling and Cancer
- Neuroendocrine Tumor Research Advances
- Neuroblastoma Research and Treatments
- Hedgehog Signaling Pathway Studies
- Renal and related cancers
- RNA Research and Splicing
- Neurogenesis and neuroplasticity mechanisms
- Lymphoma Diagnosis and Treatment
- RNA modifications and cancer
- Chronic Lymphocytic Leukemia Research
- Cholesterol and Lipid Metabolism
- Histone Deacetylase Inhibitors Research
- Neurological diseases and metabolism
- Biochemical and Molecular Research
- Protein Kinase Regulation and GTPase Signaling
University of Milan
2016-2025
University of Milano-Bicocca
2009-2013
Italian Association for Cancer Research
2011
The initiation of puberty is driven by an upsurge in hypothalamic gonadotropin-releasing hormone (GnRH) secretion. In turn, GnRH secretion depends on the development a complex neuroendocrine network during embryonic life. Although delayed (DP) affects up to 2% population, highly heritable, and associated with adverse health outcomes, genes underlying DP remain largely unknown. We aimed discover regulators whole-exome sequencing 160 individuals 67 multigenerational families our large,...
Abstract T‐cell acute lymphoblastic leukemia (T‐ALL) and lymphoma (T‐LBL) share common morphological immunophenotypic features are treated with similar therapeutic approaches. Nonetheless, they show distinct clinical presentations, suggesting that may represent two different biological entities. To investigate the genetic characteristics of T‐LBL T‐ALL, we used genomic transcriptional profiling Genome‐wide gene expression profiling, performed on 20 10 T‐ALL diagnostic specimens, revealed...
ABSTRACT The cohesin complex plays crucial roles in DNA repair, chromatid separation, and gene transcription regulation. Pathogenic variants cohesins or dysfunctional transcriptional regulators lead to cohesinopathies, a broader group of disorders including Cornelia de Lange Spectrum (CdLSp), for which the prevalence cancer cases remains unclear. Here, we aimed assess oncological events CdLSp elucidate role predisposition. We developed custom next‐generation sequencing (NGS) panel targeting...
The cohesin complex performs essential cellular functions including regulation of chromosome cohesion, chromatin organization and DNA repair. Somatic pathogenetic variants in genes, such as STAG2, have been associated with cancer, but their contribution to brain tumorigenesis is unclear. Here, we report the presence STAG2 glioblastoma medulloblastoma patients determine that loss human cells leads damage apoptosis. Treatment inhibitors Poly ADP-ribose polymerase (PARP), which are used treat...
Protein kinase CK2 (CK2) is a highly conserved and ubiquitous involved in crucial biological processes, including proliferation, migration, differentiation. holoenzyme tetramer composed by two catalytically active (α/α') regulatory (β) subunits exerts its function on broad range of targets. In the brain, it regulates different steps neurodevelopment, such as neural differentiation, neuritogenesis, synaptic plasticity. Interestingly, mutations have been recently linked to neurodevelopmental...
ABSTRACT Gonadotropin-releasing hormone (GnRH) deficiency (GD) is a disorder characterized by absent or delayed puberty, with largely unknown genetic causes. The purpose of this study was to obtain and exploit gene expression profiles GnRH neurons during development unveil novel biological mechanisms determinants underlying GD. Here, we combined bioinformatic analyses immortalized primary embryonic neuron transcriptomes exome sequencing from GD patients identify candidate genes implicated in...
The positive regulatory (PR) domain containing 13 (PRDM13) putative chromatin modifier and transcriptional regulator functions downstream of the transcription factor PTF1A, which controls GABAergic fate in spinal cord neurogenesis hypothalamus. Here, we report a recessive syndrome associated with PRDM13 mutation. Patients exhibited intellectual disability, ataxia cerebellar hypoplasia, scoliosis, delayed puberty congenital hypogonadotropic hypogonadism (CHH). Expression studies revealed...
<b><i>Introduction:</i></b> Gonadotropin-releasing hormone (GnRH) deficiency causes hypogonadotropic hypogonadism (HH), a rare genetic disorder that impairs sexual reproduction. HH can be due to defective GnRH-secreting neuron development or function and may associated with other clinical signs in overlapping syndromes. With most of the cases being idiopathic, genetics underlying is still largely unknown. <b><i>Objective:</i></b> To assess...
ABSTRACT Gonadotropin-releasing hormone (GnRH) neurons regulate puberty onset and sexual reproduction by secreting GnRH to activate maintain the hypothalamic-pituitary-gonadal axis. During embryonic development, migrate along olfactory vomeronasal axons through nose into brain, where they project median eminence release GnRH. The secreted glycoprotein SEMA3A binds its receptors neuropilin (NRP) 1 or NRP2 position these for correct neuron migration, with an additional role NRP co-receptor...
HDL (high-density lipoprotein) and its major protein component, apoA-I (apolipoprotein A-I), play a unique role in cholesterol homeostasis immunity. ApoA-I deficiency hyperlipidemic, atheroprone mice was shown to drive accumulation inflammatory cell activation/proliferation. The present study aimed at investigating the impact of on lipid deposition local/systemic inflammation normolipidemic conditions.ApoE deficient mice, apoE/apoA-I double (DKO) DKO overexpressing human apoA-I, C57Bl/6J...
Abstract Innervation of the hypothalamic median eminence by Gonadotropin-Releasing Hormone (GnRH) neurons is vital to ensure puberty onset and successful reproduction. However, molecular cellular mechanisms underlying development pubertal timing are incompletely understood. Here we show that Semaphorin-6A strongly expressed eminence-resident oligodendrocytes positioned adjacent GnRH neuron projections fenestrated capillaries, required for innervation onset. In vitro in vivo experiments...
Abstract Background the protein phosphatase 3 catalytic subunit alpha ( PPP3CA ) gene encodes for isoform of calcineurin subunit, which controls phosphorylation status many targets. Currently, 23 pathogenic variants are known, with clinical manifestations varying by mutation type and domain. Results through whole exome sequencing, we found two de novo in : a frameshift variant predicted leading to truncated Pt.1 splicing Pt.2 associated mild phenotype. is ubiquitously expressed...
The coordinated and pulsatile secretion of gonadotropin-releasing hormone (GnRH) plays a central role in vertebrate reproductive function. development the hypothalamo-pituitary-gonadal (HPG) axis is characterized by complex network molecular signals that controls, at first, migration GnRH neurons along nose, through cribriform plate, up to frontal lobe. This migratory process orchestrated several factors including anosmin-1, polysialylated form neural cell adhesion molecule, γ-amino butyric...