Disease Focus: Neurological Disorders
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 […]
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 […]
Role of the NMD RNA Decay Pathway in Maintaining the Stem-Like State
A subset of intellectual disability cases in humans are caused by mutations in an X-linked gene essential for a quality control mechanism called nonsense-mediated RNA decay (NMD). Patients with mutations in this gene—UPF3B—commonly have not only ID, but also schizophrenia, autism, and attention-deficit/hyperactivity disorder. Thus, the study of UPF3B and NMD may provide insight into […]
Modeling Alexander disease using patient-specific induced pluripotent stem cells
Alexander disease (AxD) is a devastating childhood disease that affects neural development and causes mental retardation, seizures and spasticity. The most common form of AxD occurs during the first two years of life and AxD children show delayed mental and physical development, and die by the age of six. AxD occurs in diverse ethnic, racial, […]
Common molecular mechanisms in neurodegenerative diseases using patient based iPSC neurons
A major medical problem in CA is the growing population of individuals with neurodegenerative diseases, including Parkinson’s (PD) and Huntington’s (HD) disease. These diseases affect millions of people, sometimes during the prime of their lives, and lead to total incapacitation and ultimately death. No treatment blocks the progression of neurodegeneration. We propose to conduct fundamental […]
Stem Cell Mechanisms Governing Discrete Waves of Gliogenesis in the Childhood Brain
White matter is the infrastructure of the brain, providing conduits for communication between neural regions. White matter continues to mature from birth until early adulthood, particularly in regions of brain critical for higher cognitive functions. However, the precise timing of white matter maturation in the various neural circuits is not well described, and the mechanisms […]
Stem cell models to analyze the role of mutated C9ORF72 in neurodegeneration
Amyotrophic lateral sclerosis (ALS) is an idiopathic adult-onset degenerative disease characterized by progressive weakness from loss of upper and lower motor neurons. Onset is insidious, progression is essentially linear, and death occurs within 3-5 years in 90% of patients. In the US, 5,000 deaths occur per year and in the world, 100,000. In October, 2011, […]
The HD iPSC Consortium: Repeat Length Dependent Phenotypes for Assay Development
Progenitor Cells Secreting GDNF for the Treatment of ALS
This project aims to use a powerful combined neural progenitor cell and growth factor approach to treat patients with amyotrophic lateral sclerosis (ALS or Lou Gehrig’s Disease). ALS is a devastating disease for which there is no treatment or cure. Progression from early muscle twitches to complete paralysis and death usually happens within 4 years. […]
Restoration of memory in Alzheimer’s disease: a new paradigm using neural stem cell therapy
Alzheimer’s disease (AD), the leading cause of dementia, results in profound loss of memory and cognitive function, and ultimately death. In the US, someone develops AD every 69 seconds and there are over 5 million individuals suffering from AD, including approximately 600,000 Californians. Current treatments do not alter the disease course. The absence of effective […]