Stage of Program: Basic or Applied Basic Research (DISC1 and many 1.0 Projects)
Overcoming barriers for airway stem cell gene therapy for Cystic Fibrosis
Research Objective This research will allow the targeting of airway stem cells for long lived gene therapy for Cystic Fibrosis and for other airway diseases Impact We will overcome the barriers to accessing airway basal stem cells for gene correction for Cystic Fibrosis (CF) and use a new gene correction strategy to correct >99% of […]
Modeling Retinitis Pigmentosa using patient-derived human iPSC organoids
Research Objective The objective of this proposal is to develop a human retinal organoid model of adRP to gain insights in pathogenesis and assess clinically relevant approaches to restore RHO protein function. Impact Upon successful completion of this study, we will have established a disease-in-a-dish model and a novel therapeutic approach towards management of the […]
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 […]
Identifying roadblocks to neural stem cell transplantation into human tissues.
Research Objective We will generate a comprehensive map of human neural stem cell differentiation profiles that will serve as a reference for enhancing neural stem cell-based therapies. Impact Our project will develop improved protocols for human neural stem cells differentiation, enhancing the fidelity, safety and robustness of future cell therapies. Major Proposed Activities Establish quantitative […]
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 […]
Engineering pluripotent stem cells for universally available, off-the-shelf T cell therapies
Research Objective Our goal is to develop new gene editing methods for producing universal, off-the-shelf, therapeutic T cells from induced pluripotent stem cells (iPSC) that can be applied to a range of diseases. Impact We will develop new gene editing approaches to overcome the block to T cell development from iPSC that occurs when key […]
Establishment of a novel approach to systematically study the dynamic organization of protein complexes in stem cells
Research Objective We focus on hiPSCs pluripotency and neurodifferentiation to develop a novel framework to allow simultaneous identification of multiple interactions between proteins and between proteins and the genome Impact Our framework will allow high-throughput queries of the organization and functionality of proteins and shift the focus towards unprecedented, multi-dimensional studies of the cellular complexity. […]
Harnessing vascular stem cells to grow and protect the human brain
Research Objective The origins of brain vascular mural cells are unknown. This proposal will identify mural stem cells in the developing human and mouse brain and determine their impact on blood brain barrier formation. Impact Brain vascular diseases can have profound impacts on long-term neurological function. This proposal will map the stages of mural stem […]
Determining how age-specific heterogeneity of human hematopoietic stem cells and megakaryocyte progenitors contribute to thrombotic disease upon aging
Research Objective Our research will determine how aging of human blood stem cells leads to dramatic increases in disorders of platelets, cells that normally prevent bleeding but form harmful clots when dysregulated. Impact Our findings have the potential to inform prevention and mitigation strategies of bleeding and clotting disorders that contribute to significant morbidity and […]