Disease Focus: Neurological Disorders
Personalized antisense oligonucleotide therapy for rare pediatric genetic disease: SCN2A
A Phase 2b Study of the Efficacy of a Novel Pro-Neurogenesis/Pro-Plasticity Drug for Bipolar Depression Using a Precision Psychiatry Approach
Lewy body dementia, 𝛼-synuclein, and cell-specific mechanisms of neurodegeneration
Research Objective We will generate insights about mechanisms by which 𝛼-synuclein leads to neurodegeneration of the forebrain and substantia nigra, regions affected in Lewy body dementias and Parkinson disease. Impact If the proposed studies are successfully achieved, they will impact our understanding of Lewy body dementias specifically and 𝛼-synucleinopathies and neurodegeneration more broadly. Major Proposed […]
Modeling of GATAD2B-associated neurodevelopmental disorder and NuRDopathies: Investigation of cellular & molecular anomalies altering neurodevelopment
Research Objective Human and animal models of NuRD-deficiency will identify NuRD-subtype function in context of neurogenesis. Multi-omic studies will identify/quantify molecular and cellular changes in NuRD-deficiency. Impact NuRD-deficiency causes several neurodevelopmental disorders (NDDs), our work will identify and quantify cellular and molecular changes in human and mouse models of corticogenesis with NuRD deficiency. Major Proposed […]
Village-based identification of human risk factors for viral neuropathogenesis
Research Objective We will identify the risk factors underlying viral infections of the fetal brain using a novel human stem cell-based platform that has the potential to accelerate basic and translational discoveries. Impact Our work will identify the biological factors that influence inter-individual differences in susceptibility and immune response to neurotropic viruses, which could inform […]
hPSC-derived enteric ganglioids for cell therapy in gastrointestinal motility disorders
Research Objective The proposed aims will enable the generation, purification and characterization of enteric neurons from diverse hiPSCs and assessment of their efficacy for cell therapy in GI motility disorders. Impact This proposal addresses a significant unmet clinical need for a cell therapy approach for gastrointestinal motility disorders such as Hirschsprung disease, achalasia and gastroparesis. […]
Defining the source of dysfunction in monogenic Intellectual Disability Syndrome neurons
Research Objective This study will use pluripotent stem cells derived from patients to determine why Intellectual Disabilities caused by mutations in chromatin regulatory proteins leads to neuronal defects. Impact Our study of intellectual disability syndromes will determine links between mutations and neuronal dysfunction Major Proposed Activities Our study of intellectual disability syndromes will determine links […]
An interactive data resource for hypothesis testing in stem cell single-cell gene expression and validation of the results with brain organoids
Research Objective We are building a "virtual molecular microscope" where anyone can quickly visualize a very recent, high-throughput molecular assay, single-cell RNA-seq and spatial gene expression studies Impact Currently, a lot of data has been published, hundreds of datasets on the cerebral cortex alone, but it takes hours to convert the datasets and look at […]
Role of ataxin-3 polyadenylation site selection in ALS neuron toxicity and disease pathogenesis
Research Objective Here we will study the role of ataxin-3 alternative polyadenylation in the pathogenesis of ALS, and test if ASOs can reduce distal polyadenylation of ataxin-3 to rescue ALS disease phenotypes Impact Our goal is to determine if ataxin-3 genetic dysregulation is a target for the development of therapies to treat ALS (Lou Gehrig's […]
Mapping the spatial and temporal responses of hESC-derived microglia to repeat mild closed head injury to identify therapeutic targets and mechanisms
Research Objective We will generate an RNA activation map of human stem cell derived microglia activation states following brain injury to then test a new gene-edited microglia peptide delivery mechanism. Impact Bottlenecks with the time and sex-dependent human microglia responses to repeat mild closed head injury and questions surrounding the delivery and efficacy of a […]