Human Stem Cell Use: iPS Cell
Transplantation of genetically corrected iPSC-microglia for the treatment of Sanfilippo Syndrome (MPSIIIA)
Research Objective This research will discover whether transplantation of stem cell-derived microglia can be used to treat Sanfilippo syndrome, a devastating and currently untreatable childhood neurological disease. Impact If successful, this research will identify a promising new therapeutic approach for Sanfilippo Syndrome and provide the first evidence that stem cell derived microglia could be used […]
Improving the efficacy and tolerability of clinically validated remyelination-inducing molecules using developable combinations of approved drugs
Research Objective The candidate is a fixed dose binary small molecule drug combination, consisting of two agents that act synergistically on a multipotent stem cell population in the CNS to stimulate remyelination. Impact The proposed studies will address bottleneck issues related to the effect size and tolerability of clinically validated remyelination drug classes. Major Proposed […]
Injectable, autologous iPSC-based therapy for spinal cord injury
Research Objective We propose to develop and validate a therapy for spinal cord injuries in which human stem cell-derived neural cells is injected into the injured spinal cord using an injectable gel. Impact Our study will address the critical need for an SCI treatment that significantly improves the neurological recovery and hence quality of life […]
Optimization of a gene therapy for inherited erythromelalgia in iPSC-derived neurons
Research Objective The goal of this grant is to develop a gene therapy for a rare painful disorder, Inherited Erythromelalgia (IEM). Impact There are currently no FDA approved drugs for IEM, which is caused by a gain-of-function mutation in a sodium channel, Nav1.7. We propose epigenetic repression of Nav1.7 to provide a cure for IEM. […]
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 […]
Human iPSC-derived chimeric antigen receptor expressing macrophages for improved cancer treatment.
Research Objective These studies will produce a new CAR-targeted iPSC-derived macrophage-based cell therapy product for treatment of refractory malignancies such as ovarian cancer. Impact These studies eliminate a bottleneck in macrophage production and enable these cells to be engineered and manufactured in a standardized, off-the-shelf manner, rather than on a patient-specific basis. Major Proposed Activities […]
A universally applicable skin sheet for Dystrophic Epidermolysis Bullosa via next-generation gene editing, iPS cell technology and tissue engineering
Research Objective We will develop a cell therapy for a rare skin disease. Patient-derived iPS cells will be genetically corrected and differentiated into epithelial sheets to be grafted on skin wounds. Impact In this proposal we will develop a universal genetic correction strategy for all COL7A1 which will be a prerequisite for the commercial viability […]
AAV9-Cas13 gene therapy for Angelman syndrome
Research Objective AAV9-Cas13 gene therapy for Angelman syndrome using a first-in-kind mechanism of action that will safely and permanently restore expression of endogenous UBE3A that is deficient in CNS neurons. Impact Angelman syndrome is a rare (1 in 15,000 births) neurogenetic disorder caused by loss of UBE3A in the brain, causing severe developmental delay, ataxia […]
Hypoxia-specific Production of Exosomes from iPSC-derivatives for Myocardial Repair
Research Objective A lead therapeutic candidate will be selected: 1) exosomes from hypoxia-injured iPSC-derived cardiomyocytes (iCMs), 2) exosomal miRNA cluster, and 3) siRNA inhibition of exosomal target gene, Notch3. Impact Effective targeted therapy to restore the injured and vulnerable myocardium is urgently needed to reduce the high mortality of HF patients. Promising discovery of iPSC […]
Small Molecules to inhibit Nemo-like Kinase for Treatment of Diamond Blackfan Anemia
Research Objective We propose to study small molecules that inhibit Nemo-like Kinase, to improve the production of red blood cells in bone marrow stem cells of children with Diamond Blackfan Anemia (DBA). Impact If small molecule NLK inhibitors are identified that are effective in improving the anemia of DBA and nontoxic, then treatment and transfusions […]