Stage of Program: Basic or Applied Basic Research (DISC1 and many 1.0 Projects)
Understanding Chemotherapy-Induced Peripheral Neuropathy Mechanisms using CRISPRi and Chemical Screens in Human iPSC-Derived Sensory Neurons
Research Objective The research objectives are to identify causal genes for chemotherapy-induced mitochondrial toxicity and neurodegeneration in sensory neurons and drugs that target this toxicity. Impact These studies will open the possibility for genetic or drug targeting to prevent and treat drug-induced peripheral neuropathies and possibly neuropathies caused by disease or inherited. Major Proposed Activities […]
The role of WNT and BMP signaling pathways in iPSC to iTenocyte step-wise differentiation for tendon repair
Research Objective Development-inspired differentiation will enable efficient and specific generation of tenocytes that can repair tendon injury, restore dysfunctional tissue, and prevent long term effects. Impact This study will eliminate heterogenous differentiation of pluripotent stem cells and will results in high yield and unified tenogenic phenotype. Major Proposed Activities Establish the mechanism by which Wnt […]
Developing a Human Model of Sporadic ALS Using Machine Learning and Robotic Microscopy
Research Objective We will develop the first human stem cell model of sporadic ALS (sALS) to identify disease mechanisms in the most common form of ALS and to discover drugs to treat the vast majority of ALS patients. Impact Failure of drugs to treat sALS may be due to the use of models of familial […]
Drug Discovery for Dilated Cardiomyopathy using Patient-Derived Human iPSCs
Research Objective Greenstone Biosciences will use patient-derived stem cells to discover safe and effective drugs for cardiovascular disease. Impact The use of patient-derived stem cells to discover novel drug targets for cardiovascular disease, identify drug candidates, and establish clinical trial in a dish to evaluate drug safety and efficacy. Major Proposed Activities Use patient-derived induced […]
Developing a microglia replacement therapy
Research Objective To develop a new cell therapy for the brain by transplanting the brain's immune cells Impact The brain cell therapy we envision could be used to treat rare genetic metabolic diseases, Multiple Sclerosis, brain tumors, as well as common neurodegenerative diseases including Alzheimer's disease. Major Proposed Activities Finding the best source of human […]
Towards a trophectoderm stem-cell model representing human blastocysts of the highest implantation potential
Research Objective To define a new reference for embryos and stem cell lines of the highest developmental potential and work towards a trophoblast stem cell model to study factors important for successful implantation Impact The molecular determinants of successful human blastocyst implantation remain unknown and trophectoderm stem cell models to study these embryo factors and […]
Development of a stem-cell based approach to interpret global effects of genetic variants contributing to neurodevelopmental disease risk
Research Objective We are developing a strategy to characterize the disease-relevance of hundreds of mutations across diverse genetic backgrounds using stem cells Impact Understanding how mutations impact cellular function can identify treatments for genetic diseases, but currently less than 1% of identified mutations have a known function. Major Proposed Activities Identify optimal conditions for SNV […]
Development of universal off-the-shelf iPSC derived dendritic cells for use as patient specific anti-tumor vaccine
Research Objective This proposal aims to develop a novel cell based vaccine for the treatment of cancer. The vaccine would be derived from stem cells and be personalized to the genetics of the patient and their cancer. Impact Success would provide proof-of-principle of a novel cell based therapy for cancers broadly. It is expected to […]
Control of OCT4 abundance and function in human stem cells
Research Objective Our work will reveal an essential pathway that establishes precise levels of the OCT4 transcription factor and protects stem cell identity despite genetic or environmental stress. Impact Our work will enhance our ability to generate and expand high-quality induced pluripotent stem cells from older patients or patients of neurodegenerative disease for use in […]
Modulation of human alveolar stem cells to promote lung regeneration and avoid pulmonary fibrosis
Research Objective Understanding regulators of human alveolar lung stem cell function will promote more normal lung regeneration after injury and avoid the nearly untreatable problem of advanced pulmonary fibrosis. Impact Idiopathic Pulmonary Fibrosis (IPF), Adult Respiratory Distress Syndrome (ARDS), and other chronic fibrotic lung disorders. Major Proposed Activities Modify human fibroblasts to create a supporting […]