A5052314064- Microtubule and mitosis dynamics
- Cancer-related Molecular Pathways
- Glioma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Mosquito-borne diseases and control
- Hedgehog Signaling Pathway Studies
- Ubiquitin and proteasome pathways
- Autophagy in Disease and Therapy
- RNA modifications and cancer
- ATP Synthase and ATPases Research
- DNA Repair Mechanisms
- Genetics and Neurodevelopmental Disorders
- Genomic variations and chromosomal abnormalities
- Endoplasmic Reticulum Stress and Disease
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Cellular Mechanics and Interactions
- Down syndrome and intellectual disability research
- MicroRNA in disease regulation
- Developmental Biology and Gene Regulation
- Neurogenesis and neuroplasticity mechanisms
- HIV Research and Treatment
- Signaling Pathways in Disease
- interferon and immune responses
- Pluripotent Stem Cells Research
University of Turin
2015-2024
Neuroscience Institute
2017-2023
Abstract Epidemiological evidence from the current outbreak of Zika virus (ZIKV) and recent studies in animal models indicate a strong causal link between ZIKV microcephaly. infection induces cell-cycle arrest apoptosis proliferating neural progenitors. However, mechanisms leading to these phenotypes are still largely obscure. In this report, we explored possible similarities transcriptional responses induced by human progenitors those elicited three different genetic mutations severe forms...
Mutations in citron (CIT), leading to loss or inactivation of the kinase protein (CITK), cause primary microcephaly humans and rodents, associated with cytokinesis failure apoptosis neural progenitors. We show that CITK induces DNA damage accumulation chromosomal instability both mammals Drosophila. CITK-deficient cells display "spontaneous" damage, increased sensitivity ionizing radiation, defective recovery from radiation-induced lesions. In cells, double-strand breaks increase...
Brain size and cellular heterogeneity are tightly regulated by species-specific proliferation differentiation of multipotent neural progenitor cells (NPCs). Errors in this process among the mechanisms primary hereditary microcephaly (MCPH), a group disorders characterized reduced brain intellectual disability. Biallelic CIT missense variants that disrupt kinase function (CITKI/KI) frameshift loss-of-function (CITFS/FS) genetic basis for MCPH17; however, catalytic activity development NPC...
Abscission is the final step of cytokinesis whereby intercellular bridge (ICB) linking two daughter cells cut. The ICB contains a structure called midbody, required for recruitment and organization abscission machinery. Final midbody severing mediated by formation secondary ingression sites, where ESCRT III component CHMP4B recruited to mediate membrane fusion. It presently unknown how cytoskeletal elements cooperate with abscission. Here, we show that F-actin associated sites necessary...
Medulloblastoma is the most common malignant brain tumor in children. Current treatment for medulloblastoma consists of surgery followed by irradiation whole neuraxis and high-dose multiagent chemotherapy, a partially effective strategy associated with highly invalidating side effects. Therefore, identification validation novel target molecules capable contrasting growth without disturbing development needed. Citron kinase protein (CITK), encoded primary microcephaly gene MCPH17, required...
Medulloblastoma (MB) is the most frequent brain tumor in children. The standard treatment consists surgery, followed by radiotherapy and chemotherapy. These therapies are only partially effective since many patients still die those who survive suffer from neurological endocrine disorders. Therefore, more needed. Primary microcephaly (MCPH) a rare disorder caused mutations 25 different genes. Centromere-associated protein E (CENPE) heterozygous cause MCPH13 syndrome. As for other MCPH genes,...
Abstract In the developing mouse forebrain, temporally distinct waves of oligodendrocyte progenitor cells (OPCs) arise from different germinal zones and eventually populate either dorsal or ventral regions, where they present as transcriptionally functionally equivalent cells. Despite that, developmental heterogeneity influences adult OPC responses upon demyelination. Here we show that accumulation DNA damage due to ablation citron-kinase cisplatin treatment cell-autonomously disrupts fate,...
Medulloblastoma (MB) is the most common malignant brain tumor in children, and it classified into four biological subgroups: WNT, Sonic Hedgehog (SHH), Group 3 4. The current treatment surgery, followed by irradiation chemotherapy. Unfortunately, these therapies are only partially effective. Citron kinase protein (CITK) has been proposed as a promising target for SHH MB, whose inactivation leads to DNA damage apoptosis. D283 D341 cell lines (Group 3/Group 4 MB) were silenced with established...
Down Syndrome (DS) is the most common genetic disorder associated with intellectual disability (ID). Excitatory neurons of DS patients and mouse models show decreased size dendritic field reduction spine density. Whether these defects are caused by cell autonomous alterations or abnormal multicellular circuitry still unknown. In this work, we explored issue culturing cortical obtained from two DS: widely used Ts65Dn less characterized Ts2Cje. We observed that, in vitro conditions, axon...
Goldberg-Shprintzen disease (GOSHS) is a rare microcephaly syndrome accompanied by intellectual disability, dysmorphic facial features, peripheral neuropathy and Hirschsprung disease. It associated with recessive mutations in the gene encoding kinesin family member 1-binding protein (KIF1BP, also known as KIFBP). The encoded regulates axon microtubules dynamics, attachment mitochondrial biogenesis, but it not clear how its loss could lead to microcephaly. We identified KIF1BP interactome of...
Introduction Medulloblastoma (MB), the most common malignant pediatric brain tumor, is currently treated with surgery followed by radiation and chemotherapy, which accompanied severe side effects, raising need for innovative therapies. Disruption of microcephaly-related gene Citron kinase (CITK) impairs expansion xenograft models as well spontaneous MB arising in transgenic mice. No specific CITK inhibitors are available. Methods Lestaurtinib, a Staurosporine derivative also known CEP-701,...
<p>The file contains three supplementary figures with legends. Figure S1: Characterization of cell lines expressing CITK-specific shRNAs. S2: The expression CITK correlates MB patients'' prognosis and is highly expressed in mouse SmoA1 MB. S3: Engineering characterization conditional inactivation mice.</p>
<div>Abstract<p>Medulloblastoma is the most common malignant brain tumor in children. Current treatment for medulloblastoma consists of surgery followed by irradiation whole neuraxis and high-dose multiagent chemotherapy, a partially effective strategy associated with highly invalidating side effects. Therefore, identification validation novel target molecules capable contrasting growth without disturbing development needed. Citron kinase protein (CITK), encoded primary...
<p>The file contains three supplementary figures with legends. Figure S1: Characterization of cell lines expressing CITK-specific shRNAs. S2: The expression CITK correlates MB patients'' prognosis and is highly expressed in mouse SmoA1 MB. S3: Engineering characterization conditional inactivation mice.</p>
<div>Abstract<p>Medulloblastoma is the most common malignant brain tumor in children. Current treatment for medulloblastoma consists of surgery followed by irradiation whole neuraxis and high-dose multiagent chemotherapy, a partially effective strategy associated with highly invalidating side effects. Therefore, identification validation novel target molecules capable contrasting growth without disturbing development needed. Citron kinase protein (CITK), encoded primary...
Medulloblastoma (MB) is the most common malignant brain tumor in children. Current treatments for MB surgery followed by irradiation of entire neuraxis together with high-dose multi-agent chemotherapy. The identification and validation novel target molecules, which doesn’t disturb normal postnatal physiology development central nervous system other tissues, are urgently needed. We have hypothesized Citron kinase (CIT-K) could be a potential treatment. Indeed, we know that CIT-K fundamental...