Disease Focus: Skeletal/Smooth Muscle disorders
Interrogating Satellite Cell and Myofiber Defects and Repair in Human DMD using Single Nuclei/Single Cell RNA Sequencing of Muscle Resident Cells
Research Objective We will describe, for the first time, human muscle satellite cell, myofiber and immune cell dynamics due to dystrophin deficiency and AAV gene therapy in human muscle at single nuclei resolution. Impact These studies will elucidate satellite stem cell and myofiber defects in Duchenne and Becker Muscular Dystrophy and determine efficacy, mechanism and […]
Engineering AAV capsids for transduction of neural and muscle stem cells
Research Objective The studies will identify and characterize new gene therapy vectors able to deliver gene editing components to stem cells. to enable treatment of diseases involving both muscle and brain. Impact New AAV capsids that target muscle and neural stem cells will enhance the number of neurological diseases able to be treated with AAV-based […]
Stimulating endogenous muscle stem cells to counter muscle wasting
Drug Discovery for Duchenne Muscular Dystrophy Using Patient-Derived Human iPSCs
Research Objective We will utilize human induced pluripotent stem cells derived from Duchenne muscular dystrophy (DMD) patients for drug testing and drug discovery for this rare genetic disease. Impact Diverse iPSC lines that recapitulate patient phenotypes will supplement preclinical studies to de-risk clinical trials while identifying a therapeutic target for DMD-associated cardiomyopathy. Major Proposed Activities […]
In Utero Treatment of Duchenne Muscular Dystrophy with Non-viral Gene Editing
Research Objective To develop a lipid nanoparticle/mRNA complex that can safely and efficiently edit muscle stem cells in utero, correct the dystrophin mutation, and develop a treatment for Duchenne muscular dystrophy Impact If successful, we will have developed an effective and low-cost treatment for Duchenne muscular dystrophy and a robust method to safely and efficiently […]
iPSC-derived smooth muscle cell progenitor conditioned medium for treatment of pelvic organ prolapse
Research Objective Conditioned media from human iPSC-derived smooth muscle cell progenitors. This media exerts paracrine effect to restore damaged vaginal wall in patients with pelvic organ prolapse. Impact Pelvic organ prolapse (POP) is characterized by the downward movement of the vagina and/or uterus through the vaginal opening. It is treated with surgery. The candidate is […]
Matrix Assisted Cell Transplantation of Promyogenic Fibroadipogenic Progenitor (FAP) Stem Cells
Research Objective We seek to develop a cell based-hydrogel therapy to improve outcomes in patients with muscle degeneration. The technology will improve muscle through sustained release of cell-based cytokines. Impact While designed for rotator cuff injuries based on the model, low back pain and spinal degeneration as well as traumatic muscle loss would be well […]
Pluripotent stem cell-derived bladder epithelial progenitors for definitive cell replacement therapy of bladder cancer
Research Objective We will 1) identify non-invasive bladder cancer patients with (pre)cancerous urothelium by single-cell RNA-seq and 2) replace this dangerous lesion with normal hESC-derived bladder progenitors. Impact Replacement of corrupted (pre)cancerous urothelium with pluripotent cell-derived normal bladder progenitors will provide a definitive treatment for bladder cancer, expected to eliminate recurrence. Major Proposed Activities To […]
Identification and Generation of Long Term Repopulating Human Muscle Stem Cells from Human Pluripotent Stem Cells
Research Objective We will molecularly and functionally define muscle stem cells in human muscle in development, juvenile and adult and develop strategies to generate the most regenerative muscle stem cells from hPSCs. Impact There is no clinically relevant cell endowed with continuous repopulation ability from hPSCs. This work could provide a cell therapy for muscle […]
Stimulating endogenous muscle stem cells to counter muscle atrophy
Research Objective Intramuscular delivery of two repurposed FDA approved drugs will activate resident muscle stem cells. This therapeutic strategy will augment regeneration and restore strength to atrophied muscles. Impact Currently effective treatments are lacking for localized muscle atrophy due to nerve injury (eg., Carpal Tunnel Syndrome) or immobilization after trauma or surgery (eg., hip or […]