A5058520074- Autism Spectrum Disorder Research
- Genetics and Neurodevelopmental Disorders
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Congenital heart defects research
- Cellular transport and secretion
- Genomic variations and chromosomal abnormalities
- 3D Printing in Biomedical Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Mosquito-borne diseases and control
- Reproductive System and Pregnancy
- Complement system in diseases
- Child Development and Digital Technology
- Epigenetics and DNA Methylation
- Neurogenetic and Muscular Disorders Research
- Neurogenesis and neuroplasticity mechanisms
- Neuroscience and Neural Engineering
- Ion Channels and Receptors
- History of Medical Practice
- Cytokine Signaling Pathways and Interactions
- RNA regulation and disease
- Virology and Viral Diseases
- Inflammatory mediators and NSAID effects
- Child Abuse and Related Trauma
- Tissue Engineering and Regenerative Medicine
Hospital Israelita Albert Einstein
2015-2024
Universidade de São Paulo
2009-2022
Hospital São Paulo
2022
Insper
2015
Rady Children's Hospital-San Diego
2010-2014
University of California, San Diego
2010-2014
Abstract Congenital Zika syndrome (CZS) causes early brain development impairment by affecting neural progenitor cells (NPCs). Here, we analyze NPCs from three pairs of dizygotic twins discordant for CZS. We compare RNA-Seq the derived CZS-affected and CZS-unaffected twins. Prior to virus (ZIKV) infection CZS babies show a significantly different gene expression signature mTOR Wnt pathway regulators, key neurodevelopmental program. Following ZIKV in vitro infection, affected individuals have...
Autism spectrum disorder is a complex and genetically heterogeneous disorder, which has hampered the identification of etiological factors in each patient and, consequently, genetic counseling for families at risk. However, last decades, remarkable advances knowledge aspects autism based on molecular research, as well development new diagnostic tools, have substantially changed this scenario. Nowadays, it estimated that using currently available tests, potential underlying cause can be...
Abstract Evaluation of expression profile in autism spectrum disorder (ASD) patients is an important approach to understand possible similar functional consequences that may underlie disease pathophysiology regardless its genetic heterogeneity. Induced pluripotent stem cell (iPSC)-derived neuronal models have been useful explore this question, but larger cohorts and different ASD endophenotypes still need be investigated. Moreover, whether changes seen vitro model reflect previous findings...
Biallelic loss-of-function mutations in the RNA-binding protein EIF4A3 cause Richieri-Costa-Pereira syndrome (RCPS), an autosomal recessive condition mainly characterized by craniofacial and limb malformations. However, pathogenic cellular mechanisms responsible for this are entirely unknown. Here, we used two complementary approaches, patient-derived induced pluripotent stem cells (iPSCs) conditional Eif4a3 mouse models, to demonstrate that defective neural crest cell (NCC) development...
The Reelin-DAB1 signaling pathway plays a crucial role in regulating neuronal migration and synapse function. Although many rare heterozygous variants the Reelin gene (RELN) have been identified patients with autism spectrum disorder (ASD), most are still of unknown clinical significance. Also, genetic data suggest that RELN alone appear to be insufficient cause ASD. Here, we describe identification functional characterization compound missense patient ASD whom previously reported...
SPOAN syndrome is a neurodegenerative disorder mainly characterized by spastic paraplegia, optic atrophy and neuropathy (SPOAN). Affected patients are wheelchair bound after 15 years old, with progressive joint contractures spine deformities. also have sub normal vision secondary to apparently non-progressive congenital atrophy. A potential causative gene was mapped at 11q13 ten ago. Here we performed next-generation sequencing in SPOAN-derived samples. While whole-exome failed identify the...
Several lines of indirect evidence, such as mutations or dysregulated expression genes related to cytoskeleton, have suggested that cytoskeletal dynamics, a process essential for axons and dendrites development, is compromised in autism spectrum disorders (ASD). However, no study has yet examined whether cytoskeleton dynamics functionally altered cells from ASD patients. Here we investigated the regulation actin stem human exfoliated deciduous teeth (SHEDs) 13 patients 8 control individuals...
Constraints for the application of MSCs bone reconstruction include restricted self-renewal and limited cell amounts. iPSC technology presents advantages over MSCs, providing homogeneous cellular populations with prolonged higher plasticity. However, it is unknown if osteogenic potential iPSCs differs from that depends on originating source. Here, we compared in vitro osteogenesis between stem cells human deciduous teeth (SHED) MSC-like SHED (iPS-SHED) dermal fibroblasts (iPS-FIB). iPS-SHED...
Copy number variations (CNVs) are an important cause of ASD and those located at 15q11-q13, 16p11.2 22q13 have been reported as the most frequent. These CNVs exhibit variable clinical expressivity 15q11-q13 also show incomplete penetrance. In present work, through multiplex ligation-dependent probe amplification (MLPA) analysis 531 ethnically admixed ASD-affected Brazilian individuals, we found that combined prevalence is 2.1% (11/531). Parental origin could be determined in 8 affected...
In recent years, accumulating evidence has shown that the innate immune complement system is involved in several aspects of normal brain development and neurodevelopmental disorders, including autism spectrum disorder (ASD). Although abnormal expression components was observed post-mortem samples from individuals with ASD, little known about patterns molecules distinct cell types developing autistic brain. present study, we characterized mRNA protein profiles a wide range components,...
Identification of the causes autism spectrum disorders (ASDs) is hampered by their genetic heterogeneity; however, different alterations leading to ASD seem be implicated in disturbance common molecular pathways or biological processes. In this scenario, search for differentially expressed genes (DEGs) between patients and controls a good alternative identify etiology such disorders. Here, we employed genome-wide expression analysis compare transcriptome stem cells human exfoliated deciduous...
Biallelic pathogenic variants in TBCK cause encephaloneuropathy, infantile hypotonia with psychomotor retardation, and characteristic facies 3 (IHPRF3). The molecular mechanisms underlying its neuronal phenotype are largely unexplored. In this study, we reported two sisters, who harbored biallelic met diagnostic criteria for IHPRF3. We provided evidence that may play an important role the early secretory pathway neuroprogenitor cells (iNPC) differentiated from induced pluripotent stem...
Prenatal exposure to maternal immune activation (MIA) has been suggested increase the probability of autism spectrum disorder (ASD). Recent evidence from animal studies indicates a key role for interleukin-17a (IL-17a) in promoting MIA-induced behavioral and brain abnormalities reminiscent ASD. However, it is still unclear how IL-17a acts on human developing cell types directly affected by signaling. In this study, we used iPSC-derived neural progenitor cells (NPCs) individuals with ASD...
Abstract Here, we describe a female patient with autism spectrum disorder and dysmorphic features that harbors complex genetic alteration, involving de novo balanced translocation t(2;X)(q11;q24), 5q11 segmental trisomy maternally inherited isodisomy on chromosome 5. All the possibly damaging effects of such alterations are discussed. In light recent findings ASD causes, hypothesis all these might be acting in orchestration contributing to phenotype is also considered. © 2012 Wiley Periodicals, Inc.
Abstract Oligogenic inheritance of autism spectrum disorder (ASD) has been supported by several studies. However, little is known about how the risk variants interact and converge on causative neurobiological pathways. We identified in an ASD proband deleterious compound heterozygous missense Reelin ( RELN ) gene, a de novo splicing variant Cav3.2 calcium channel CACNA1H gene. Here, using iPSC-derived neural progenitor cells (NPCs) heterologous expression system, we show that leads to...