A5076232765- Neurogenesis and neuroplasticity mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetics and Neurodevelopmental Disorders
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Nitric Oxide and Endothelin Effects
- Genomics and Rare Diseases
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Congenital heart defects research
- RNA Interference and Gene Delivery
- Hedgehog Signaling Pathway Studies
- Fetal and Pediatric Neurological Disorders
- Wnt/β-catenin signaling in development and cancer
- RNA regulation and disease
- Genetic and Kidney Cyst Diseases
- Retinoids in leukemia and cellular processes
- Virology and Viral Diseases
- Bone health and treatments
- Microtubule and mitosis dynamics
- Nicotinic Acetylcholine Receptors Study
- Neuroscience and Neuropharmacology Research
- Fibroblast Growth Factor Research
- Autophagy in Disease and Therapy
- S100 Proteins and Annexins
- Cancer-related gene regulation
Northwestern University
2019-2024
University of California, San Diego
2013-2019
Howard Hughes Medical Institute
2013-2019
Rockefeller University
2015-2019
Children’s Institute
2019
Universidad Nacional Autónoma de México
2008-2011
Prolonged activation of glutamate receptors leads to excitotoxicity. Several processes such as reactive oxygen species (ROS) production and the calcium-dependent protease, calpain, contribute glutamate-induced damage. It has been suggested that ROS-producing enzyme, NADPH oxidase (NOX), plays a role in Studies have reported NOX after NMDA receptor stimulation during excitotoxic damage, but non-NMDA metabotropic is unknown. We evaluated roles different subtypes on neuronal death induced by...
PACS1 syndrome is a neurodevelopmental disorder characterized by intellectual disability and distinct craniofacial abnormalities resulting from de novo p.R203W variant in phosphofurin acidic cluster sorting protein 1 (PACS1). known to have functions the endosomal pathway nucleus, but how affects developing neurons not fully understood. Here we differentiated stem cells towards neuronal models including cortical organoids investigate impact of syndrome-causing on neurodevelopment. While few...
Activity-dependent neurotransmitter switching engages genetic programs regulating transmitter synthesis, but the mechanism by which activity is transduced unknown. We suppressed in single neurons embryonic spinal cord to determine whether glutamate-gamma-aminobutyric acid (GABA) cell autonomous. Transmitter respecification did not occur, suggesting that it homeostatically regulated level of surrounding neurons. Graded increase number silenced cultures led graded decrease expressing GABA,...
PACS1 syndrome is a neurodevelopmental disorder resulting from unique de novo p.R203W variant in Phosphofurin Acidic Cluster Sorting protein 1 (PACS1). encodes multifunctional sorting required for localizing furin to the trans-Golgi network. Although few studies have started investigate impact of variant, mechanisms by which affects neurodevelopment are still poorly understood. In recent years, ASD patient-derived brain organoids been increasingly used identify pathogenic and possible...
Abstract Programmed cell death (PCD) has been defined as an active, controlled process in which cells participate their own demise. Apoptosis, or type I PCD, widely characterized, both morphologically and biochemically. More recently, autophagy, the self‐digesting mechanism involved removal of cytoplasmic long‐lived proteins, death, II PCD is occurring with autophagic features. Neurons can undergo more than one a backup when traditional pathway inhibited response to particular death‐inducing...
To identify causes of the autosomal-recessive malformation, diencephalic-mesencephalic junction dysplasia (DMJD) syndrome.
Protocadherins (PCDHs) are cell adhesion molecules that regulate many essential neurodevelopmental processes related to neuronal maturation, dendritic arbor formation, axon pathfinding, and synaptic plasticity. Biallelic loss-of-function variants in PCDH12 associated with several disorders (NDDs). Despite the highly deleterious outcome resulting from loss of PCDH12, little is known about its role during brain development disease. Here, we show severely impairs cerebral organoid development,...
Abstract Objective PCDH19 ‐related epilepsy is characterized by a distinctive pattern of X‐linked inheritance, where heterozygous females exhibit seizures and hemizygous males are asymptomatic. A cellular interference mechanism resulting from the presence both wild‐type mutant neurons in patients or mosaic carriers variants has been hypothesized. We aim to investigate seizure susceptibility progression Pchd19 mouse model. Methods assessed Pcdh19 model using three acute induction paradigms....
Reactive oxygen species (ROS) are produced early during apoptosis of cerebellar granule neurons induced by low potassium (K5) and staurosporine (Sts). In addition, K5 Sts activate NADPH oxidases (NOX). Recently, we described that induce apoptotic volume decrease (AVD) at a time when ROS generation NOX activity occur. the present study, evaluated relationship between ionic fluxes AVD. Here, showed K5- Sts-induced AVD was inhibited antioxidants direct production Moreover, inhibitors eliminated...
The MAST family of microtubule-associated serine-threonine kinases (STKs) have distinct expression patterns in the developing and mature human mouse brain. To date, only MAST1 has been conclusively associated with neurological disease, de novo variants individuals a neurodevelopmental disorder, including mega corpus callosum.
Abstract Neuronal apoptotic death involves the participation of reactive oxygen species (ROS), but their sources have not been completely elucidated. Previous studies demonstrated that ROS‐producing enzyme NADPH oxidase is present in neuronal cells and this could participate death. Cerebellar granule neurons (CGN) undergo apoptosis when are transferred from a medium with 25 mM KCl (K25) to 5 (K5) or they treated staurosporine (ST). Under these conditions, CGN dependent on ROS production. In...
Neurodevelopmental disorders are characterized by complex phenotypes that often result from concomitant dysregulation of cell proliferation, differentiation, or other crucial developmental processes. Here, we present a protocol to quantify differentiation progenitor populations during early stages neurogenesis in induced pluripotent stem (iPSC)-derived cerebral organoids. We describe steps for organoid and maturation, sample preparation, immunofluorescence, imaging analysis using...
Organotypic slice culture is a powerful in vitro model that mimicks vivo conditions more closely than dissociated primary cell cultures. In early postnatal development, cerebellar Purkinje cells are known to go through vulnerable period, during which they undergo programmed death. Here, we provide detailed protocol perform mouse organotypic this critical time. The slices further labeled assess survival and the efficacy of neuroprotective treatments. This method can be extremely valuable...