Project Objective: Research Insights
Molecular Characterization and Functional Exploration of Hemogenic Endothelium
Hematopoietic cells are responsible for generating all cell types present in the blood and therefore critical for the provision of oxygen and nutrients to all the tissues in the body. Blood cells are also required for defense against microorganisms and even for the recognition and elimination of tumor cells. Because blood cells have a relatively […]
Deep phenotyping of human brain organoid models of autism spectrum disorder to unravel disease heterogeneity and develop biomarkers and treatments
Research Objective We will uncover pathways through which ASD mutations cause disease and close the gap from disease research to therapeutic testing using organoids, primary human neurons, machine learning and AAVs. Impact Our studies are impactful because outcomes will lead to therapeutic avenues to pursue for ASD treatment. 1 in 22 children in California is […]
Mapping and modeling endothelial cell fate decisions for pulmonary arterial hypertension
Research Objective We will build a foundational model and experimental platform to catalog all genes that promote and protect against PAH, with the potential to extend to many other developmental and disease processes. Impact The studies aim to identify genetic targets for PAH therapy and develop a predictive model to accelerate stem cell research and […]
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 […]
Immune cloaking of human stem cell-derived insulin-producing cells for curative cell therapy without immunosuppression
Research Objective The goal of our project is to generate cells for replacement therapy in patients that have reduced ability to trigger the immune response in the recipient and therefore escape rejection. Impact We test a novel molecule that reduces immune activation upon transplantation of allogeneic stem cell products that can improve graft survival and […]
Neuroimmune interactions in the developing human brain
Research Objective This project will identify mechanisms by which immune cells regulate human brain development, and use stem cell derived models to identify pathological changes induced by congenital virus infection. Impact Neurodevelopmental disorders caused by immune cell perturbations will be impacted by the fundamental understanding of how immune system controls normal development of the brain. […]
Interrogating Satellite Cell and Myofiber Defects and Repair in Human DMD using Single Nuclei/Single Cell RNA Sequencing of Muscle Resident Cells
Research Objective We will describe, for the first time, human muscle satellite cell, myofiber and immune cell dynamics due to dystrophin deficiency and AAV gene therapy in human muscle at single nuclei resolution. Impact These studies will elucidate satellite stem cell and myofiber defects in Duchenne and Becker Muscular Dystrophy and determine efficacy, mechanism and […]
Harnessing the rejuvenating capacity of pregnancy-associated factors to restore aged stem cell function
Research Objective Elucidation of pregnancy-related factors that mitigate cellular senescence and enhance regeneration has far-reaching implications for understanding the mechanisms of aging and rejuvenation. Impact The study will address the long-standing knowledge gaps related to the mechanisms of pro-regenerative impact of pregnant milieu and female muscle stem cell senescence Major Proposed Activities Isolation of female […]
Investigating the SGF29/SAGA complex in regulation of normal and cancer stem cells
Research Objective This study will address gaps in our understanding of how normal and cancer stem cells differ in their epigenetic states, helping develop new cancer-stem-cell-targeting therapis. Impact The long-term impact of our studies is the understanding of mechnistic differences between normal and cancer stem cells and the development of new therapies. Major Proposed Activities […]
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 […]