Stage of Program: Basic or Applied Basic Research (DISC1 and many 1.0 Projects)
Mass Cytometry to Delineate the Human Muscle Stem Cell Hierarchy and Dysfunction in Aging
Aging is characterized by a decline in skeletal muscle mass and strength (sarcopenia), coupled with an accumulation of fat tissue, impairing mobility and quality of life in 45% of individuals over 65 years of age. In aged mice, the regeneration defect arises in part from a diminished regenerative capacity of resident muscle stem cells (MuSCs). […]
Mechanisms of human induced neuronal cell reprogramming
We and other groups have recently shown that it is possible to convert skin cells from foreskin of newborns into nerve cells that closely resemble nerve cells of the brain in terms of both shape and functional properties. If it were possible to also reprogram human adult skin cells into similarly functional nerve cells, we […]
Non-invasive live imaging of stem cell signature metabolic states
Stem cells in tissues exhibit unique metabolic states that could distinguish them from other more specialized cells. Using a new type of microscopy we can image the metabolic states of cells in living tissues and, therefore, attempt to identify stem cell populations. Because stem cells can give rise to tumors that are metabolically very different […]
Molecular regulation of stem cell potency
The field of stem cell biology as it applies to regenerative medicine requires a detailed understanding of what controls stem cell function. Our fundamental interest is in the molecular pathways that control how potent as a stem is in terms of its ability to make new tissues in response to injury and disease. We have […]
Directed Differentiation of Specialized Endothelial Cells
Vascular endothelial cells (EC) or endothelial progenitor cells (EPC) derived from stem cells could potentially lead to a variety of clinically relevant therapeutic applications, including various strategies for treating heart and vascular diseases. However, because EC exhibit a variety of functionally distinct subphenotypes, it is important to be able to generate the appropriate endothelial type. […]
Biophysical Determinants of Early Embryonic Stem Cell Fate Specification
Regenerative therapies require effective differentiation of stem cells to cell types that are functionally identical to those found in vivo. Many current differentiation protocols merely involve optimization of proteins added to the culture media, but do not consider the microenvironmental context in which cells differentiate during development or tissue repair. When we include the biophysical […]
Engineered matrices for control of lineage commitment in human pancreatic stem cells
Patients with end-stage type 1 diabetes (T1D) can be effectively managed by allogeneic islet transplantation. However, a severe cadaveric organ shortage greatly limits use of this promising procedure. Stem cells have the potential to provide a solution to this bottleneck because of their ability to self-renew and differentiate into islet β-cells. Although progress has been […]
Metabolically-driven epigenetic changes in iPSC reprogramming
Generation of induced pluripotent stem cells (iPSCs) from somatic cells through cellular reprogramming offers tremendous potential for therapeutics, the study of disease states, and elucidation of developmental processes. Central to the process of generating a pluripotent cell from a somatic cell is an energy-dependent epigenetic reconfiguration event that must occur to produce iPSCs with characteristics […]
Role of intracytoplasmic pattern recognition receptors in HSC engraftment
The research performed through this project is very important for the fields of solid organ and bone marrow transplantation because it focuses on a potential new target to increase engraftment of stem cells. Currently, patients that receive stem cell transplants from a non-identical donor must take medications to suppress their immune system; otherwise the stem […]
Paracrine and synaptic mechanisms underlying neural stem cell-mediated stroke recovery
Stem cell therapy holds promise for the almost million Americans yearly who suffer a stroke. Preclinical data have shown that human neural stem cells (hNSCs) aid recovery after stroke, resulting in a major effort to advance stem cell therapy to the clinic, and we are currently transitioning our hNSC product to the clinic for stroke […]