Therapeutic/Technology: Exploring stem cell mechanisms
Human endothelial reprogramming for hematopoietic stem cell therapy.
The current roadblocks to hematopoietic stem cell (HSC) therapies include the rarity of matched donors for bone marrow transplant, engraftment failures, common shortages of donated blood, and the inability to expand HSCs ex vivo in large numbers. These major obstacles would cease to exist if an extensive, bankable, inexhaustible, and patient-matched supply of blood were […]
Human Induced Pluripotent Stem Cell-Derived Cardiovascular Progenitor Cells for Cardiac Cell Therapy.
Despite therapeutic advances, cardiovascular disease remains a leading cause of mortality and morbidity in California. Regenerative therapies that restore normal function after a heart attack would have an enormous societal and financial impact. Although very promising, regenerative cardiac cell therapy faces a number of challenges and technological hurdles. Human induced pluripotent stem cells (hiPSC) allow […]
Regulation of Epidermal Self-Renewal and Differentiation by Histone and DNA Demethylases.
Tissue specific stem and progenitor cells exist to replenish the tissue it resides during normal homeostasis or during regeneration from a wound. Disease and aging leads to a depletion of these stem and progenitor cells, which can impede the ability of the body to regenerate itself. Thus, an understanding of the mechanisms of how tissue […]
Epigenetic regulation of human cardiac differentiation
Each cell type in our body has its own identity. This identity allows a heart cell to contract repetitively, and a brain cell to conduct nerve impulses. Each cell type gains its identity by turning on or off thousands of genes that together give the cell its identity. Understanding how these sets of genes are […]
Mechanism and Utility of Direct Neuronal Conversion with a MicroRNA-Chromatin Switch
Many human diseases and injuries that affect the brain and nervous system could potentially be treated by either introducing healthy neurons or persuading the cells that normally provide supporting functions to become functioning neurons. A number of barriers must be traversed to bring these goals to practical therapies. Recently our laboratory and others have found […]
Asymmetric stem cell division oriented by a local self-renewing signal
When stem cells divide, the two daughter cells have a choice. Commonly, one of the daughter cells becomes a new stem cell while the other one will be more specialized (or differentiated). This property — the ability to generate more stem cells (self-renewal) while making differentiated cells simultaneously — defines a stem cell. Stem cells […]
3D Modeling of Retina using Polymer Scaffolds for Understanding Disease Pathogenesis
Inherited retinal degenerations result in visual loss in patients as early as in their adolescence. Retinitis Pigmentosa includes a group of such degenerations which run in families and can result in legal blindness by 40 years of age. Even though we know by now a number of gene mutations which can cause these disorders, we […]
Modeling disease in human embryonic stem cells using new genetic tools
The use of stem cells or stem cell-derived cells to treat disease is one important goal of stem cell research. A second, important use for stem cells is the creation of cellular models of human development and disease, critical for uncovering the molecular roots of illness and testing new drugs. However, a major limitation in […]
Investigation of the role of O-GlcNAcylation in SOX2 function during reprogramming
Induced pluripotent stem cells (iPSCs) are a potential source of material for cell replacement therapies. Thus, achieving maximal efficiency of reprogramming will be important for cellular medicine. In this submission we propose to test whether manipulating the mammalian glucose sensing pathway. The enzyme OGT is part of the glucose-sensing pathway and is necessary in pluripotent […]
Induction of Pluripotent Stem Cell-Derived Pacemaking Cells
Currently, over 350,000 patients per year with abnormal heart rhythm receive electronic pacemakers to restore their normal heart beat. Electronic pacemakers do not respond to the need for changing heart rate in situations such as exercise and have limited battery life, which can be resolved with biopacemakers. In this proposed project, we will examine methods […]