Award Type: Fundamental Mechanisms (Track 1)
In vitro modeling of human motor neuron disease
Motor neuron (MN) diseases such as spinal muscular atrophy and amyotrophic lateral sclerosis lead to progressive degeneration of MNs, presenting first with muscle weakness, followed by locomotor defects and frequently death due to respiratory failure. While progress has been made in identifying genes associated with MN degeneration, the molecular and cellular processes underlying disease onset […]
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 […]
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 […]
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 […]
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 […]
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 […]
Metabolic regulation of cardiac differentiation and maturation
Cells in the body take up nutrients from their environment and metabolize them in a complex set of biochemical reactions to generate energy and replicate. Control of these processes is particularly important for heart cells, which need large amounts of energy to drive blood flow throughout the body. Not surprisingly, the nutritional requirements of heart […]
A novel druggable mechanism to safeguard stem cell genome
Safeguarding the genome is essential for cells’ proper functions, and more importantly for safe and efficacious applications involving pluripotent stem cells and adult stem cells. However, how pluripotent or somatic stem cells maintain genome integrity during self-renewal, differentiation, and reprogramming is still largely unknown. We recently identified a small molecule drug that exhibits unprecedented abilities […]
Generation of a functional thymus to induce immune tolerance to stem cell derivatives
Stem cell research offers the promise of replacing missing or damaged tissues in the treatment of disease. Stem-cell-derived transplants still face problems with rejection as in traditional organ transplants. Several drugs can prevent rejection but also suppress the immune system, leaving patients vulnerable to infections and cancer. To avoid rejection without using drugs requires re-educating […]