Program Type: Discovery
Identification and isolation of transplantable human hematopoietic stem cells from pluripotent cell lines; two steps from primitive hematopoiesis to transplantable definitive cells, and non-toxic conditioning of hosts for hematopoeitic stem cell transp…
A goal of stem-cell therapy is to transplant into a patient “tissue-specific” stem cells, which can regenerate a particular type of healthy tissue (e.g., heart or blood cells). A major obstacle to this goal is obtaining tissue-specific stem cells that (1) are available in sufficient numbers; and (2) will not be rejected by the recipient. […]
A small molecule tool for reducing the malignant potential in reprogramming human iPSCs and ESCs
This research project aims to solve a key bottleneck in the use of differentiated human embryonic stem cells and induced pluripotent stem cells for the regeneration and replacement of diseased or damaged tissues. This bottleneck is the potential of unintended transplants containing failed-to-differentiate stem cells developing into benign growths called teratomas, or worse, malignant teratocarcinomas. […]
Development of a clinical-grade extracorporeal liver support system using human induced pluripotent stem cell-derived hepatic cells
Liver failure is the fourth leading cause of adult death in California. Because liver cells can regenerate, some patients with liver failure could be saved without having to undergo organ transplantation if their liver function could be supported temporarily. Here, we propose to develop a device to support these patients called the “extracorporeal liver support […]
User-friendly predictive molecular diagnostic assays for quality control of stem cell derivatives for transplantation and drug discovery
Three years ago, with help from CIRM funding, we developed an assay. This is a genomics-base diagnostic assay, similar to those now used for diagnosing cancers; but in our case, it is designed to analyze human ES and iPS cells. The assay is very simple to use; researchers use microarrays to profile the genes that […]
Development of a Relevant Pre-Clinical Animal Model as a Tool to Evaluate Human Stem Cell-Derived Replacement Therapies for Motor Neuron Injuries and Degenerative Diseases
Motor neurons degenerate and die as a consequence of many conditions, including trauma to the spinal cord and its nerve roots and degenerative diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy. Paralysis and in many cases death may result from a loss of motor neurons. No effective treatments are available for these patients. […]
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 […]
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 […]