Therapeutic/Technology: Model system development

A new precision medicine based iPSC-derived model to study personalized intestinal fibrosis treatments in pediatric patients with Crohn’s disease

Research Objective We propose to discover a tool that will utilize patient specific iPSC-derived human mini-guts to identify personalized antifibrotic treatments in pediatric Crohn’s disease patients Impact The major bottleneck in intestinal fibrosis research is the difficulty in obtaining patient-specific biologically relevant cells for in vitro modeling. This iPSC-derived tool would overcome it. Major Proposed […]

A novel hybrid CRISPR tool for gene network perturbation and hiPSC engineering

Research Objective A CRISPR-based tool for simultaneous up- and downregulation of many (~5-20) genes, and a computational tool using scRNA-seq data to predict which genes to perturb for efficacious cell-type conversion. Impact A critical bottleneck to the creation of specific cell types from stem cells (and related therapies) is our current inability to make cells […]

A screen for drugs to protect against chemotherapy-induced hearing loss, using sensory hair cells derived by direct lineage reprogramming from hiPSCs

Research Objective Development of a screen using inner ear sensory hair cell-like cells made by direct lineage reprogramming, for discovering drugs to ameliorate hearing loss during cancer chemotherapy. Impact Hearing loss, both adult and pediatric, due to life-saving cisplatin chemotherapies. Lack of human inner ear hair cells for drug discovery purposes and disease modeling. Major […]

Human Cardiac Chip for Assessment of Proarrhythmic Risk

Research Objective This proposal will develop patient specific ‘heart-on-a-chip’ devices that will significantly impact early screening of drugs to accurately predict drug-induced proarrhythmia and toxicity. Impact Patient specific ‘heart-on-a-chip’ device will significantly reduce the cost of bringing a new drug candidate to market while improving efficacy. Major Proposed Activities To improve the maturity of human […]

An IPSC cell based model of macular degeneration for drug discovery.

Research Objective Towards a cure for age related blindness, we propose to create a human stem cell based model to screen for drugs that are protective against Age related macular degeneration (AMD). Impact With up to 11 million people in the United States affected by AMD, effective treatments against macular degeneration could address vision loss […]

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. […]