Goldman Laboratories
Recent studies have substantially expanded our conception of the types of progenitor cells that continue to reside in the adult nervous system, and their respective roles in the normal maintenance of the brain and spinal cord. In the adult human, neural stem cells persist within the forebrain ventricular zone, and give rise to a variety of more restricted progenitor cell types.
The major progenitor pools of the adult human forebrain, each of which we have isolated to purity, include ventricular zone neuronal progenitor cells, hippocampal neuronal progenitors, and glial progenitor cells of the white matter. We are studying each of these cell types from the standpoints of their unique patterns of gene expression, their responses to their local tissue environments, and their behavior upon engraftment in models of both development and disease. As our knowledge of the biology and control of adult neural progenitor cells has become more extensive, we have begun to target, induce and implant these cells for therapeutic purposes.
We are thus engaged in a broad spectrum of gene and cell-based strategies for repairing the damaged or diseased nervous system. Our emphasis is on targeting and mobilizing endogenous stem and progenitor cells of the adult brain and spinal cord, for purposes of structural repair. For this purpose, we study the biology of adult progenitor cells in systems as diverse as the songbird neostriatum and the adult human temporal lobe, and their potential therapeutic roles in a correspondingly varied range of disease models. The Division’s current emphases include:
• Isolation and molecular characterization of different progenitor cell types of both the fetal and adult human CNS.
• Isolation and telomerase immortalization of developmentally-restricted neuronal progenitor cells from fetal CNS, such as those generating midbrain dopaminergic neurons, forebrain cholinergic neurons, and spinal cord motor neurons.
• Use of both native and immortalized neuronal progenitors in experimental models of cell type-selective neurodegenerative diseases, such as Parkinson’s and ALS
• Inducing endogenous progenitor cells as a means of treatment, for example mobilizing striatal progenitors in Huntington’s disease models, and dentate progenitors in dementia.
• Glial and oligodendrocyte progenitor-based cell therapy in models of perinatal leukodystophies and storage diseases.
• Combined neuronal and glial progenitor implant-based strategies in experimental models of spinal cord injury.
• Development of new cell-specific vectors for directing therapeutic gene expression to defined neuronal and glial cell targets.
The group’s work is supported by 3 NIH R01 Awards, a Javits Award, and foundations that include the National MS Society, the Michael J. Fox Foundation, the Christopher Reeve Paralysis Foundation, the New York State Spinal Cord Research Program, the Hereditary Disease Foundation and its Cure Huntington’s Disease initiative, and the Mathers Charitable
Foundation. Biotech and pharmaceutical collaborators include Merck Research Labs, Berlex Bioscience, Regeneron, Aventis, Qthera, Curis, and others, advancing both the scope and translational intent of these studies. |
