Disease Focus: Neurological Disorders
Generation of disease models for neurodegenerative disorders in hESCs by gene targeting
The ability to target a specific locus in the mouse genome and to alter it in a specific fashion has fundamentally changed experimental design and made mice the preeminent model for studying human diseases . However, pathogenesis in humans have unique pathways that may not be revealed by only using mouse or other animal models. […]
Directed Evolution of Novel AAV Variants for Enhanced Gene Targeting in Pluripotent Human Stem Cells and Investigation of Dopaminergic Neuron Differentiation
Human embryonic stem cells (hESCs) and induced pluripotent stem (iPS) cells have considerable potential as sources of differentiated cells for numerous biomedical applications. The ability to introduce targeted changes into the DNA of these cells – a process known as gene targeting – would have very broad implications. For example, mutations could readily be introduced […]
North Bay CIRM Shared Research Laboratory for Stem Cells and Aging
Age-related diseases of the nervous system are major challenges for biomedicine in the 21st century. These disorders, which include Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis and stroke, cause loss of neural tissue and functional impairment. Currently, there is no cure for these devastating neurological disorders. A promising approach to the treatment of […]
Defining the Isoform-Specific Effects of Apolipoprotein E on the Development of iPS Cells into Functional Neurons in Vitro and in Vivo
GOALS We propose to determine the effects of different forms of apoE on the development of induced pluripotent stem (iPS) cells into functional neurons. In Aim 1, iPS cells will be generated from skin cells of adult knock-in (KI) mice expressing different forms of human apoE and in humans with different apoE genotypes. In Aim […]
Mechanisms in Choroid Plexus Epithelial Development
Buried deep inside the brain are cells known as choroid plexus epithelial (CPe) cells. Although not as famous as other cells in the nervous system, CPe cells perform a large number of important jobs that keep the brain and spinal cord healthy. They produce the fluid (known as cerebrospinal fluid, or CSF) that bathes the […]
High throughput modeling of human neurodegenerative diseases in embryonic stem cells
An important class of neurological diseases predominantly affects spinal motor neurons, the neurons that control muscle movement. The most well known of these motor neuronopathies is Amyotrophic Lateral Sclerosis (ALS), commonly referred to as Lou Gehrig’s disease for the famous Yankee first baseman who died of the disease. The first symptoms of ALS are usually […]
Derivation of Parkinson’s Disease Coded-Stem Cells (PD-SCs)
Parkinson’s disease (PD) is currently the most common neurodegenerative movement disorder, severely debilitating approximately 1-2% of the US population. The disease is caused by a selective loss of dopamine-producing neurons located in a specific region of the brain. This loss leads to significant motor function impairment and age-dependent tremors. Unfortunately there is currently no cure […]
Generation of clinical grade human iPS cells
The therapeutic use of stem cells depends on the availability of pluripotent cells that are not limited by technical, ethical or immunological considerations. The goal of this proposal is to develop and bank safe and well-characterized patient-specific pluripotent stem cell lines that can be used to study and potentially ameliorate human diseases. Several groups, including […]
Establishment of Frontotemporal Dementia Patient-Specific Induced Pluripotent Stem (iPS) Cell Lines with Defined Genetic Mutations
We propose to generate induced pluripotent stem (iPS) cells from skin cells derived from human subjects with frontotemporal dementia (FTD). FTD accounts for 15–20% of all dementia cases and, with newly identified genetic causes, is now recognized as the most common dementia in patients under 65 years of age. FTD patients suffer progressive neurodegeneration in […]
Development of Induced Pluripotent Stem Cells for Modeling Human Disease
Human embryonic stem cells (hESC) hold great promise in regenerative medicine and cell replacement therapies because of their unique ability to self-renew and their developmental potential to form all cell lineages in the body. Traditional techniques for generating hESC rely on surplus IVF embryos and are incompatible with the generation of genetically diverse, patient or […]