Disease Focus: Neurological Disorders
Generation of forebrain neurons from human embryonic stem cells
The goal of this proposal is to generate forebrain neurons from human embryonic stem cells. Our general strategy is to sequentially expose ES cells to signals that lead to differentiation along a neuronal lineage, and to select for cells that display characteristics of forebrain neurons. These cells would then be used in transplantation experiments to […]
Using human embryonic stem cells to treat radiation-induced stem cell loss: Benefits vs cancer risk
A variety of stem cells exist in humans throughout life and maintain their ability to divide and change into multiple cell types. Different types of adult derived stem cells occur throughout the body, and reside within specific tissues that serve as a reserve pool of cells that can replenish other cells lost due to aging, […]
MicroRNAs in Human Stem Cell Differentiation and Mental Disorders
Many mental disorders are closely associated with problems that occur during brain development in early life. For instance, by 2 years of age, autistic children have larger brains than normal kids, likely due to, at least in part, excess production of neurons and support cells, the building blocks of the nervous system. In autistic brains, […]
The Immunological Niche: Effect of immunosuppressant drugs on stem cell proliferation, gene expression, and differentiation in a model of spinal cord injury.
Our understanding of the effect of immunosuppressive agents on stem cell proliferation and differentiation in the central nervous system is limited. Indeed, even the necessity for long-term immunosuppression to promote the survival of stem cells grafted into the “immunoprivileged” central nervous system (CNS) is unknown. Grafting multipotent stem cells into the injured CNS often results […]
Identifying small molecules that stimulate the differentiation of hESCs into dopamine-producing neurons
In this application, we propose to identify small molecule compounds that can stimulate human embryonic stem cells to become dopamine-producing neurons. These neurons degenerate in Parkinson’s disease, and currently have very limited availability, thus hindering the cell replacement therapy for treating Parkinson’s disease. Our proposed research, if successful, will lead to the identification of small […]
In vitro differentiation of hESCs into corticospinal motor neurons
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, fatal neurological disease that leads to the degeneration of motor neurons in the brain and in the spinal cord. There are currently 20,000 ALS patients in the United States, and 5,000 new patients are diagnosed every year. Unfortunately no cure has been found for ALS. The only […]
Cellular Reprogramming: Dissecting the Molecular Mechanism and Enhancing Efficiency
Pluripotent stem cells have a remarkable potential to develop into virtually any cell type of the body, making them a powerful tool for the study or direct treatment of human disease. Recent demonstration that induced pluripotent stem (iPS) cells may be derived from differentiated adult cells offers unprecedented opportunities for basic biology research, regenerative medicine, […]
Systemic Protein Factors as Modulators of the Aging Neurogenic Niche
Approaches to repair the injured brain or even prevent age-related neurodegeneration are in their infancy but there is growing interest in the role of neural stem cells in these conditions. Indeed, there is hope that some day stem cells can be used for the treatment of spinal cord injury, stroke, or Parkinson’s disease and stem […]
MGE Enhancers to Select for Interneuron Precursors Produced from Human ES Cells
There are now viable experimental approaches to elucidate the genetic and molecular mechanisms that underlie severe brain disorders through the generation of stem cells, called iPS cells, from the skin of patients. Scientists are now challenged to develop methods to program iPS cells to become the specific types of brain cells that are most relevant […]
Role of the microenvironment in human iPS and NSC fate and tumorigenesis
Multipotent Neural Stem Cells (NSC) can be derived from adult central nervous system (CNS) tissue, embryonic stem cells (ESC), or iPSC and provide a partially committed cell population that has not exhibited evidence of tumorigenesis after long term CNS transplantation. Transplantation of NSC from these different sources has been shown by multiple investigators in different […]