Disease Focus: Genetic Disorder
Efficacy and safety of cryopreserved autologous CD34+ HSC transduced with EFS lentiviral vector encoding for human ADA gene in ADA-SCID subjects
In ADA-SCID, allogeneic hematopoietic (blood) stem cell transplants from non-matched sibling donors are a high risk procedure. Additionally, the efficacy of chronic enzyme replacement therapy is uncertain in the long-term. A team at UCLA is using a patient’s own blood stem cells to try and rebuild the damaged immune systems of patients with ADA-SCID. They will use what’s […]
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 […]
Modeling and understanding alveolar hypoplasia in Down syndrome using iPSCs-derived alveolar type II cells
Research Objective Understanding alveolar progenitor cell defects in T21 and the genes/pathways associated with them will allow for developing therapeutic approaches for individuals with DS. Impact Although trisomy 21 affects multiple organ system, respiratory complications are the major cause of death in kids and adults with DS. The causes of lung disease in DS remain […]
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 […]
Functional genomics to study cellular convergence across ASD risk genes in neurodevelopment
Research Objective Our objective is to enable scalable genetic screening to study how neurogenesis is impacted by risk genes implicated in human psychiatric disorders. Impact We will develop and apply state-of-the-art genomic analysis to seek mechanisms and disease modifying solutions. Major Proposed Activities Identifying and validating efficient gRNA for gene editing Identify risk gene effects […]
Drivers of trophoblast stem/progenitor cell identity in human placenta
Research Objective This proposal will elucidate the mechanisms that identify a stem/progenitor cell population in the human placenta. Impact This proposal addresses our current knowledge gap on human placental development related to formation of the maternal/fetal interface during pregnancy, and placenta-associated pregnancy complications. Major Proposed Activities Identification of DNA regions, called enhancers, regulating placenta stem/progenitor […]
Drug Discovery for Duchenne Muscular Dystrophy Using Patient-Derived Human iPSCs
Research Objective We will utilize human induced pluripotent stem cells derived from Duchenne muscular dystrophy (DMD) patients for drug testing and drug discovery for this rare genetic disease. Impact Diverse iPSC lines that recapitulate patient phenotypes will supplement preclinical studies to de-risk clinical trials while identifying a therapeutic target for DMD-associated cardiomyopathy. Major Proposed Activities […]
Hematopoietic Stem Cell Gene Editing for X-linked Agammaglobulinemia (XLA)
Translational Candidate Autologous CD34+ hematopoietic stem and progenitor cells (HSPC) with BTK gene insertion for treatment of X-linked agammaglobulinemia (XLA). Area of Impact The candidate will provide improved outcomes for patients with XLA, by allowing autologous transplantation with reduced intensity conditioning Mechanism of Action The Drug Product has biological activity of hematopoietic stem cells (HSC) […]
Ex Vivo Modified Hematopoietic Stem Cells to Treat Danon Disease
Translational Candidate The candidate is CD34+ HSPCs transduced ex vivo with a LAMP2 lentiviral vector. Area of Impact Danon Disease, Lysosomal Storage Diseases, Drug Development for Rare Disease Mechanism of Action Engrafted HSPC progeny will supply normal LAMP2B to the heart, liver, muscle, and brain via lysosomal cross-correction. Specifically, macrophages transfer lysosomes containing LAMP2B to […]
CRISPR/Cas9-mediated gene editing of Hematopoietic stem and progenitor cells for Friedreich’s ataxia
Translational Candidate Autologous human CD34+ HSPC of patients with Friedreich’s ataxia, modified ex vivo using CRISPR/Cas9 to remove the GAA expansion mutation in frataxin Area of Impact Friedreich’s ataxia (FRDA) for which there is no effective treatment available Mechanism of Action The proposed therapy intervention is intended to impact the target indication of Friedreich's ataxia […]