Disease Focus: Genetic Disorder
Functional Genomic Analysis of Chemically Defined Human Embryonic Stem Cells
Regenerative medicine holds the promise that tissues can be engineered in vitro and then transplanted into patients to treat debilitating diseases. Human Embryonic Stem Cells differentiate into a wide array of adult tissue types and are thought to be the best hope for future regenerative therapies. This grant has three main goals: 1. The creation […]
Derivation and characterization of human ES cells from FSHD embryos
Facioscapulohumeral muscular dystrophy (FSHD) is the third most common hereditary muscular dystrophy. It is autosomal dominant, meaning that if one of the parents has the disease, their children have a 50:50 chance of getting it, too. FSHD is characterized by progressive weakness and atrophy of facial, shoulder and upper arm musculature, which can spread to […]
Molecular Characterization of hESC and hIPSC-Derived Spinal Motor Neurons
One of the main objectives of stem cell biology is to create physiologically relevant cell types that can be used to either facilitate the study of or directly treat human disease. Tremendous progress towards these goals has been made in the area of motor neuron disease and spinal cord injury through the findings that motor […]
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 […]
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) […]