Disease Focus: Blood Disorders
Targeted Gene Editing in the Treatment of X-Linked Hyper-IgM Syndrome
Research Objective We are seeking to develop site-specific hematopoietic stem cell gene therapy with autologous transplant as a definitive treatment option for X-linked Hyper-IgM Syndrome. Impact These studies would bring stem cell gene therapy for X-HIGM closer to the clinic, as there are currently no options for those without an HLA match or with infections […]
Protein tyrosine phosphatase – sigma inhibitors for hematopoietic regeneration
Research Objective We propose to develop a lead small molecule inhibitor of PTPσ, a receptor expressed by human blood stem cells, for the purpose of promoting human hematopoietic regeneration. Impact Systemic administration of a PTPσ inhibitor can accelerate hematologic recovery in thousands of patients who have received myelosuppressive chemo- or radiotherapy. Major Proposed Activities Generate […]
GENE EDITING FOR FOXP3 IN HUMAN HSC
Research Objective CRISPR/Cas9 mediated FOXP3 gene editing in patient-derived hematopoietic stem cells as a cure for IPEX syndrome Impact FOXP3 mutation in IPEX syndrome leads to immune system dysregulation. Allogeneic HSCT, the only available treatment, has very poor outcomes including GvHD and low immune reconstitution. Major Proposed Activities Demonstrate specificity of targeted insertion of FOXP3 […]
Optimizing self-renewal signaling kinetics to stabilize ex vivo hematopoietic stem cell expansion
Research Objective We aim to develop conditions for stable expansion of blood stem cells outside of the body Impact Blood stem cells are a rare but necessary cell type for curative bone marrow transplantation and related gene therapies. Stable blood stem cell expansion will increase therapy availability and success Major Proposed Activities Validate a fully […]
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 […]
Modulating Liver Sinusoidal Endothelial Cell Permeability to Enhance Engraftment of Endothelial Cell Progenitors for the Treatment of Hemophilia A
Research Objective We aim to demonstrate that regulators of endothelial cell permeability can foster engraftment of endothelial cell progenitors in the liver sinusoids leading to production of Factor VIII. Impact Our work would provide conceptual proof that a cell based therapy for hemophilia A is possible and should be pursued. Major Proposed Activities Demonstrate that […]
New Methods for the Chemical Expansion of Hematopoietic Stem and Progenitor Cells
Research Objective We will develop a new agent that can increase the production of hematopoietic stem and progenitor cells and determine how the compound functions Impact We aim to develop a method to achieve the highest fold expansion of hematopoietic stem cells from a single unit of cord blood achieved to date increasing the supply […]
Development of a Noninvasive Prenatal Test for Beta-Hemoglobinopathies for Earlier Stem Cell Therapeutic Interventions
Translational Candidate An earlier, safer noninvasive prenatal screening test for β-thalassemia and sickle cell disease to identify candidates for prenatal stem cell therapy Area of Impact Our test is safer and can be conducted earlier than the current methods of prenatal testing (e.g. chorionic villous sampling and amniocentesis) Mechanism of Action Our test uses next […]
Development of a Noninvasive Prenatal Test for Beta-Hemoglobinopathies for Earlier Stem Cell Therapeutic Interventions
Translational Candidate An earlier, safer noninvasive prenatal screening test for β-thalassemia and sickle cell disease to identify candidates for prenatal stem cell therapy Area of Impact Our test is safer and can be conducted earlier than the current methods of prenatal testing (e.g. chorionic villous sampling and amniocentesis) Mechanism of Action Our test uses next […]
Toward a Cure for Gaucher Disease Type 1: Autologous Transplantation of Genome Edited Hematopoietic Stem Cells
Translational Candidate Autologous blood stem cells edited to restore glucocerebrosidase expression Area of Impact Gaucher disease type 1 (non-neuronopathic) Mechanism of Action To treat Gaucher disease, autologous blood stem cells undergo genome editing to restore the deficient enzyme. Reintroducing these edited cells replaces the patient's bone marrow, establishing a lasting enzyme reservoir. The bone marrow […]