California Institute of Regenerative Medicine (CIRM)
NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA (BSCRC)
Rose Hills Foundation
Ablon Scholars Foundation
Understanding Human Developmental Somitogenesis and Myogenesis
Somites form during embryonic development and give rise to various cell and tissue types, such as skeletal muscles, ribs, vertebrae, brown fat and skin of the back. We have transcriptionally profiled human presomitic and somitic mesoderm, which has improved our knowledge on this critical process and enabled us to efficiently derive human somite cells from pluripotent stem cells in a dish. We are now using a similar strategy to study different stages of human developmental myogenesis to improve our understanding of myogenic specification in vivo and enhance myogenic cell derivation in vitro.
Maturation of human pluripotent stem cells towards skeletal muscle progenitor cells and muscle fibers
The developmental status of human pluripotent stem cell (hPSC) derived skeletal muscle cells is not well defined. By using directed differentiation and RNA sequencing, we are are identifying targets to mature HPSC derived muscle to fetal and adult satellite cells.
Gene editing with CRISPR/Cas9 for Duchenne Muscular Dystrophy
We reprogrammed DMD patient fibroblasts to DMD-hiPSCs and devised a correction strategy applicable to the majority of DMD patients. Using CRISPR/Cas9, we removed exons 45-55 to restore the dystrophin reading frame in DMD-hiPSCs and demonstrated that directed differentiation of these hiPSCs to skeletal and cardiac muscle restored dystrophin expression in vitro and in vivo.
Tools and Technology Development for Pluripotent Stem Cells and Differentiation
We have several projects aimed as using tailored engineering platforms to enhance our ability to reprogram, expand and/or differentiate hPSCs to generate robust and stable differentiated progenitors for downstream in vitro and in vivo applications including high throughput screening, nanoparticles, engineered surfaces for stem cell differentiation and imaging reporter systems
Transplantation of hPSC-derived skeletal muscle progenitor cells for muscular dystrophy therapies
The functional and therapeutic potential of human fetal, adult, and hPSC derived skeletal muscle progenitor cells (SMPCs) in vivo is not known. We are identifying the most engraftable cell type, signaling factors, and niche components to increase the potential of cell based therapy using SMPCs. This work will be combined with CRIPSR/Cas9 gene editing to develop personalized approaches for patients with muscle disease.