A5046211998- Axon Guidance and Neuronal Signaling
- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Hippo pathway signaling and YAP/TAZ
- Cellular Mechanics and Interactions
- Neurological diseases and metabolism
- Nerve injury and regeneration
- Erythrocyte Function and Pathophysiology
- Neurogenesis and neuroplasticity mechanisms
- Photoreceptor and optogenetics research
- bioluminescence and chemiluminescence research
- Cancer Research and Treatments
- Botany, Ecology, and Taxonomy Studies
- Viral-associated cancers and disorders
- CNS Lymphoma Diagnosis and Treatment
- Zebrafish Biomedical Research Applications
- Caveolin-1 and cellular processes
- Lymphoma Diagnosis and Treatment
- Plant Diversity and Evolution
- Neuroinflammation and Neurodegeneration Mechanisms
- Glioma Diagnosis and Treatment
- Lipid Membrane Structure and Behavior
- biodegradable polymer synthesis and properties
- Protist diversity and phylogeny
- Alzheimer's disease research and treatments
Icahn School of Medicine at Mount Sinai
2019-2025
Allen Institute for Brain Science
2019-2025
Universidade de São Paulo
2011-2015
Universidade Federal de Juiz de Fora
2010-2012
Glioblastoma (GBM) is a malignant brain tumor with diffuse infiltration. Here, we demonstrate how GBM cells usurp guidance receptor Plexin-B2 for confined migration through restricted space. Using live-cell imaging to track negotiating microchannels, reveal endocytic vesicle accumulation at cell front and filamentous actin assembly rear in polarized manner. These processes are interconnected require signaling. We further show that governs membrane tension other features such as endocytosis,...
Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disorder affecting motoneurons and the SOD1G93A transgenic mice are widely employed to study disease physiopathology therapeutic strategies. Despite cellular biochemical evidences of an early motor system dysfunction, conventional behavioral tests do not detect impairments in SOD1 mouse model. We evaluated changes behavior ALS by doing analyses tail elevation, footprint, automatic recording activities means infrared motion...
Abstract The transition from unicellular to multicellular organisms poses the question as when genes that regulate cell-cell interactions emerged during evolution. receptor and ligand pairing of plexins semaphorins regulates cellular in a wide range developmental physiological contexts. We surveyed here genomes eukaryotes non-bilaterian bilaterian Metazoa performed phylogenetic analyses gain insight into evolution plexin semaphorin families. Remarkably, we detected choanoflagellates,...
The regeneration of peripheral nerves is guided by tracks formed through an interplay many cell types, but the underlying signaling pathways remain unclear. Here, we demonstrate that macrophages are mobilized ahead Schwann cells in nerve bridge after transection injury to participate building tracks. This requires function guidance receptor Plexin-B2, which robustly up-regulated infiltrating injured nerves. Conditional deletion Plexin-B2 myeloid lineage resulted not only macrophage...
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that leads to widespread motor neuron death, general palsy and respiratory failure. The most prevalent sporadic ALS form not genetically inherited. Attempts translate therapeutic strategies have failed because the described mechanisms of are based on animal models carrying specific gene mutations thus do address ALS. In order achieve better approach study human disease, induced pluripotent stem cell...
Abstract During morphogenesis, molecular mechanisms that orchestrate biomechanical dynamics across cells remain unclear. Here, we show a role of guidance receptor Plexin-B2 in organizing actomyosin network and adhesion complexes during multicellular development human embryonic stem neuroprogenitor cells. manipulations affect contractility, leading to changes cell stiffness cytoskeletal tension, as well cell-cell cell-matrix adhesion. We have delineated the functional domains Plexin-B2,...
Amyotrophic Lateral Sclerosis (ALS) is an adult-onset and fast progression neurodegenerative disease that leads to the loss of motor neurons. Mechanisms selective neuron in ALS are unknown. The early events occurring spinal cord may contribute death not described, neither astrocytes participation pre-symptomatic phases disease. In order identify events, we performed a microarray analysis employing whole mouse genome platform evaluate gene expression pattern lumbar cords transgenic SOD1(G93A)...
Abstract Infiltrative growth is a major cause of high lethality malignant brain tumors such as glioblastoma (GBM). We show here that GBM cells upregulate guidance receptor Plexin-B2 to gain invasiveness. Deletion in stem limited tumor spread and shifted invasion paths from axon fiber tracts perivascular routes. On cellular level, adjusts cell adhesiveness, migratory responses different matrix stiffness, actomyosin dynamics, thus empowering leave stiff bulk infiltrate softer parenchyma....
Early molecular events related to cytoskeleton are poorly described in Amyotrophic Lateral Sclerosis (ALS), especially the Schwann cell (SC), which offers strong trophic support motor neurons. Database for Annotation, Visualization and Integrated Discovery (DAVID) tool identified cytoskeleton-related genes by employing Cellular Component Ontology (CCO) a large gene profiling of lumbar spinal cord sciatic nerve presymptomatic SOD1(G93A) mice. One five CCO terms were from deregulated 40 days...
Longitudinal tracking of tumor growth using noninvasive bioluminescence imaging (BLI) is a key approach for studies in vivo cancer models, with particular relevance investigations malignant gliomas rodent intracranial transplant paradigms. Akaluciferase (Akaluc) new BLI system higher signal strength than standard firefly luciferase (Fluc). Here, we establish Akaluc as sensitive method glioma expansion.We engineered lentiviral vector expression high-grade cell lines, including patient-derived...
Abstract Semaphorins and plexins are cell surface ligand/receptor proteins that affect cytoskeletal dynamics in metazoan cells. Interestingly, they also present Choanoflagellata, a class of unicellular heterotrophic flagellates forms the phylogenetic sister group to Metazoa. Several members choanoflagellates capable forming transient colonies, whereas others reside solitary inside exoskeletons; their molecular diversity is only beginning emerge. Here, we surveyed genomics data from 22...
ABSTRACT Glioblastoma (GBM) is a malignant brain tumor with uncontrolled invasive growth. Here, we demonstrate how GBM cells usurp guidance receptor Plexin-B2 to gain biomechanical plasticity for polarized migration through confined space. Using live-cell imaging track negotiating microchannels, reveal active endocytosis at cell front and filamentous actin assembly rear propel constrictions. These two processes are interconnected governed by that orchestrates cortical membrane tension, shown...
The present study investigated the effects of anthraquinone derivative (O,O′-bis-(3′-iodopropyl)-1,4-dihidroxyanthraquinone — DIPDHAQ), mitoxantrone analog, in an experimental autoimmune encephalomyelitis (EAE) model. results showed that DIPDHAQ treatment improved clinical signs disease (n = 10; vehicle: 3.8 ± 0.3; DIPDHAQ: 1.4 0.9). improvement was associated with a decrease inflammatory cells, demyelination, IL-17, IFN-γ, IL-12p40, IL-6, TGF-β, CCL5 and CCL20 levels spinal cord. presented...
Schwann cells are the main source of paracrine support to motor neurons. Oxidative stress and mitochondrial dysfunction have been correlated neuron death in Amyotrophic Lateral Sclerosis (ALS). Despite involvement early neuromuscular disruption ALS, detailed molecular events a dying-back triggering unknown. Sciatic nerves presymptomatic (60-day-old) SOD1(G93A) mice were submitted high-density oligonucleotide microarray analysis. DAVID demonstrated deregulated genes related death,...
Abstract Glioblastoma is a malignant brain tumor of uncontrolled proliferation and infiltration. GBM stem cells (GSCs) are constantly challenged by confined spaces during their migration through the parenchyma. Understanding factors that drive GSC (CM) thus critical for effective drug development. Using microchannel devices, we showed GSCs adept at squeezing narrow constrictions faster speed than non-constricted spaces. During CM, cytoskeletal components plasma membrane self-organize to...
O linfoma B intravascular de grandes células (IVLBCL) é uma doença rara caracterizada pela proliferação neoplásica linfoides no interior capilares. Relatamos um caso IVLBCL em paciente jovem do sexo feminino com comprometimento bilateral da glândula suprarrenal. exame imuno-histoquímico confirmou o IVLBCL. A afinidade entre órgãos endócrinos e hipótese levantada para explicar a correlação verificada Além disso, associação sintomatologia descrita parece refletir padrão que poderá auxiliar...
SUMMARY During multicellular organization, individual cells need to constantly respond environmental cues and adjust contractile adhesive forces in order maintain tissue integrity. The signaling pathways linking biochemical mechanics are unclear. Here, we show that Plexin-B2 regulates mechanochemical integration during organization. In human embryonic stem (hESCs), controls cell shape geometry both 2D epithelial colony 3D spheroid aggregates by regulating actomyosin contractility...
Abstract Diffuse invasion of glioblastoma (GBM) cells into brain tissue is a key factor for its high lethality. GBM cell migration affected by functions plexins, which are transmembrane receptors semaphorins that regulate adhesion and cytoskeletal dynamics. Expression Plexin-B2 upregulated in correlates with malignancy. We show here activity regulates biomechanical properties cells, promoting invasive growth. increased the capacity to invade as dispersed single reducing cell-cell...
Abstract Longitudinal tracking of tumor growth using non-invasive bioluminescence imaging (BLI) is a key approach for in vivo cancer studies, but the current method firefly luciferase (Fluc) BLI has quantitative limitations, as it only suited detection tumors considerable sizes at advanced stage, typically order >105 cells. Recently, Akaluciferase (Akaluc) been developed an alternative system that offers higher signal strength and better light penetration tissue due to its red-shifted...
Abstract Infiltrative growth is a major cause of the high lethality malignant brain tumors such as glioblastoma (GBM). The study contribution biomechanical processes to GBM invasion an emerging field. We show here that cells upregulate guidance receptor Plexin-B2 gain invasiveness by modulating their properties. Deletion in stem limited tumor spread and shifted paths from axon fiber tracts perivascular routes. On cellular level, adjusts cell adhesiveness, migratory responses different matrix...