Institute for Brain Disorder and Neural Regeneration

The Institute's primary biomedical research focus is on defining the regional localization and the biological properties of neural stem cells during embryonic and postnatal development and in the mature and the aging mammalian brain. Stem cells are also being utilized as "biological probes" to elucidate the pathogenesis of a spectrum of complex and poorly understood acquired and genetic nervous system disorders. In these prototypical disorders, distinct profiles of regional stem cells or their more lineage-restricted neuronal or glial progeny undergo irreversible cellular dysfunction and premature death or cellular transformation in response to acute or more chronic injury signals. Further, the knowledge gained from these multidisciplinary studies is being channeled into the design of innovative genetic, epigenetic and stem cell associated regenerative therapies. Research scientists within the Institute are in the process of defining the dynamic roles of environmental factors, cell-cell signaling pathways and cell autonomous cues in promoting stem cell activation, expansion, lineage restriction, lineage commitment, cell cycle exit and terminal differentiation. Institute investigators have identified specific transcription factor codes that endow the progeny of specific stem cell subpopulations with their unique cellular properties.

These insights have already allowed Institute scientists to "reprogram" specific regional stem and progenitor cell subpopulations both in vitro and in vivo to acquire the cellular properties of specific neuronal and glial subtypes. Specific complements of these discrete neural cell subtypes are invariably affected in different classes of neurological diseases including neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease and motor neuron disease/ amyotrophic lateral sclerosis, primary brain tumors, demyelinating and dysmyelinating disorders, stroke, HIV infection, epilepsy, diabetes mellitus and associated metabolic syndromes and premature aging. Other Institute investigators have also utilized embryonic stem cells, both to define initial stages of neural induction and patterning of the neural tube that have previously been difficult to examine experimentally, and as therapeutic reagents for those diseases of the nervous system in which multiple regional neuronal and glial subtypes are targeted. The overall aim of these studies is to identify innovative approaches to brain repair by activation of latent neural stem cell pools throughout the neuraxis to engage in selective regeneration of those cell types and neural network connections that have been compromised in specific disease states in the adult brain. The ability to selectively activate, elaborate and modulate these latent developmental programs to participate in selective neural regenerative responses within discrete temporal intervals and spatial domains will help to reestablish functional neural networks that preserve the integrity of previously acquired informational traces.

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