Jean de Vellis Ph.D.
Director; Associate Director for Cellular and Molecular Neuroscience and Neurogenomics
UCLA Intellectual and Developmental Disabilities Research CenterUniversity of California, Los Angeles
760 Westwood Plaza, 68-177 NPI
375D, NRB
733222
Los Angeles, CA 90024-1759
310-825-9395 (tel)
[email protected]
Biography/Curriculum Vitae:
Research Interests:
Mechanisms of glial pathogenesis and repair in developmental neurodegenerative diseases
Narrative of Current Research Efforts:
de Vellis's research has been focused on the development of neurons, astrocytes and oligodendrocytes(OL), their dysfunctions in white matter developmental disorders and their potential for regeneration. During development, intrinsic genomic mechanisms of commitment and lineage restriction are modulated by environmental signals in both embryonic and postnatal cells.
Studies of neural progenitor in culture and neural cell transplants have been instrumental in assessing the potential of cell grafts for CNS repair. We have previously demonstrated in a myelin-deficient rat model that direct brain delivery of specific factors known to participate in oligodendrogenesis and myelinogenesis, in combination with OL progenitor transplants, provide a promising approach for myelin repair. In vivo IGF-I acts synergistically with transferrin to promote proliferation and specification of neural stem/progenitor cells into OL that express myelin genes in the normal and the myelin-deficient rat brain. This research augurs well for the potential of cell replacement therapy in genetic and environmental dys- and de-myelinating human diseases, such as Pelizaeus Merzbacher's, leukodystrophies, Canavan's and traumatic CNS injury.
In the adult, demyelinating diseases, as in Multiple Sclerosis, are devastating maladies that affect the integrity of the insulating membrane myelin and the axon. Although, the adult CNS has been considered to be depleted of cells capable of remyelination, a combination of 4 growth factors was found to stimulate the proliferation of adult OL progenitors in a mouse demyelinating model. In white matter diseases, OL encounter stressors and inflammatory cytokines. Activation of several genes, transcription factors and newly synthesized proteins can change the fate of cells to live or die.
We identified potential mechanisms involved in the clearance of denatured proteins produced by stress in OL: an antioxidant dehydrogenase, HSP70, Rab3a and ubiquitin. These findings may help developing future therapy against loss of OL in degenerative disorders.
Major Honors and Awards:
Representative Publications:
Givogri MI, de Planell M, Galbiati F, Superchi D, Gritti A, Vescovi A, de Vellis J and Bongarzone ER (2006) Notch signaling in astrocytes and neuroblasts of the adult subventricular zone in health and after cortical injury. Dev Neurosci, 28:81-91.
Espinosa-Jeffrey A, Kumar S, Zhao PM, Awosika O, Agbo C, Huang A, Chang R and De Vellis J (2002) Transferrin regulates transcription of the MBP gene and its action synergizes with IGF-1 to enhance myelinogenesis in the md rat. Dev Neurosci, 24:227-41.
Tzeng SF, Bresnahan JC, Beattie MS and de Vellis J (2001) Upregulation of the HLH Id gene family in neural progenitors and glial cells of the rat spinal cord following contusion injury. J Neurosci Res, 66:1161-72.
Lee M, Lelievre V, Zhao P, Torres M, Rodriguez W, Byun JY, Doshi S, Ioffe Y, Gupta G, Espinosa de los Monteros AE, de Vellis J and Waschek J (2001) Pituitary adenylyl cyclase-activating polypeptide stimulates DNA synthesis but delays maturation of oligodendrocyte progenitors. J Neurosci, 21:3849-59.
Cheng JD and de Vellis J (2000) Oligodendrocytes as glucocorticoids target cells: functional analysis of the glycerol phosphate dehydrogenase gene. J Neurosci Res, 59:436-45.
Created 7/30/2005 by
Last modified 2/14/2019 by Oksana Klimova
