Therapeutic/Technology: Model system development
A new phenotypic screening platform that identifies biologically-relevant targets and lead compounds for the treatment of Parkinson’s disease
Research Objective Demonstrate that our HitFinder™ library can be screened for phenotypic changes in A53T-IPSC-derived dopaminergic neurons and use a secondary handle to identify the targets responsible. Impact This technology combines phenotypic screening and target-ID eliminating the need to bias assays and/or screening libraries permitting application directly in iPSC-derived cells. Major Proposed Activities Prepare screening […]
Enhanced Branching Morphogenesis and Pluripotent Cell Lineage Differentiation for Pediatric Regenerative Therapies
Research Objective Approximately 20,000 babies are born annually with kidney disease; the long-term outcome is poor. These studies address new ways to develop mini-kidney structures for transplantation to induce repair. Impact ~85% of people on the organ waitlist are in need of a kidney and there are insufficient donors. There is a pressing need to […]
Generation of human airway stem cells by direct transcriptional reprogramming for disease modeling and regeneration
Research Objective We will generate human airway stem cells by direct transcriptional reprogramming of fibroblasts. We will use these induced airway stem cells to model motile cilia disease in a dish. Impact Generating airway stem cells through reprogramming will create a scalable and editable cell line from which we can derive airway epithelium, thus enabling […]
Reprogramming human stem cells for blood cell generation
Research Objective To create a universal donor blood cell line that can be used to produce human red blood cells for transplantation. Impact Successful completion of this work would create a safe, unrestricted source of universal donor human blood cells that could be used to improve healthcare and save lives throughout the world. Major Proposed […]
Organoid Modeling of Human Cortical Microcircuits
Research Objective The proposed studies will develop three-dimensional cell culture methods for creating human brain neural circuits for disease research and drug discovery. Impact The proposed research will develop a new research platform for studying how neurons in the human brain function, how neurological disease subverts this activity, and how we might find new therapies. […]
Blood Brain Barrier (BBB)-on-Chip: Development and validation of a novel iPS-based microfluidic model of the human BBB
Research Objective to develop and systematically characterize a novel model of the human BBB using a microfluidic device (chip) and cells derived from induced pluripotent stem cells (iPSCs). Impact The success of the proposed research will provide a novel, highly attractive model for screening of molecules to treat neurological disorders and for personalized medicine in […]
Genome editing for causation and reversion of MPN-associated mutations in human hematopoietic stem cells
Research Objective Use gene editing to create tools for the study of mechanisms by which patient-observed mutations lead to myeloproliferative neoplasms. Impact Editing reagents will yield new insight into how acquired MPN-associated mutations cause disease by overproduction of various cell types and pave the way for gene editing therapies to reverse MPNs. Major Proposed Activities […]
Cell Villages and Clinical Trial in a Dish with Pooled iPSC-CMs for Drug Discovery
Translational Candidate Human stem cells in a dish engineered into heart cells to supplement, refine, reduce, and/or ultimately replace human clinical trials. Area of Impact Increase genetic diversity of preclinical studies in human samples to derisk clinical trials and save time and costs. Mechanism of Action We will have several non-invasive human-derived stem cells collected […]
Human iPSC-derived micro-heart muscles for high-throughput cardiac drug discovery
Translational Candidate In vitro miniaturized array of heart muscle amenable for use in efficient high-throughput drug discovery and screening campaigns. Area of Impact Effective high-throughput screening of drugs on human heart muscles does not exist, hindering the discovery of therapeutics to treat heart failure. Mechanism of Action Current approaches for drug discovery often miss a […]
Embryonic stem cell-based generation of rat models for assessing human cellular therapies
Heart failure, diabetes and neurodegenerative diseases are among the leading causes of death and disability worldwide. These diseases are characterized by the loss of specific cell types and can be treated and potentially cured with stem cell-based therapies. Before human stem cells can be used in clinical trials, however, their safety and efficacy need to […]