James E. Goldman, MD, PhD

Our lab has been tracing cell lineages in the developing mammalian CNS to study the origins of neurons and glia from immature neuroectodermal cells. Using recombinant retroviruses to transfer genes into progenitor cells, we have followed the migration and differentiation of immature cells of germinal zones in vivo and have determined time- and location-specific patterns of glial development. We are examining what roles environmental vs. lineage-controlled factors play in specifying cell fates. We are particularly interested in how progenitors migrate through the developing brain, focusing on molecular mechanisms that regulate the direction, the beginning and the cessation of migration. Our lab is also starting to examine these same type of mechanisms as they apply to glial tumor migration through the brain.

We have also been studying responses of glial cells to pathological changes in the CNS. We are particularly interested in how the immature glia that reside in the adult CNS remyelinate axons after a demyelinating insult. We are also studying Alexander disease, a leukodystrophy in which the brain does not myelinate properly and astrocytes accumulate massive amounts of intermediate filaments and the small heat shock proteins, alpha ß-crystallin and hsp27. Recent studies show that Alexander disease is caused by mutations in the gene encoding GFAP, an intermediate filament expressed by astrocytes. We are studying how these mutations result in the accumulation of filaments, an accompanying astrocyte stress response, and the inability of the brain to myelinate properly.

Selected publications:

• Gensert, J.M., and Goldman, J.E. Remyelination by endogenous progenitors in the adult rat CNS. Neuron 19: 197-203 (1997).

• Messing, A., Head, M.W., Galles, K., Galbreath, E.J., Goldman, J.E., and Brenner, M. Fatal encephalopathy with astrocyte inclusions in GFAP transgenic mice. Am. J. Pathol. 152: 391-398 (1998).

• Koyama, Y. and Goldman, J.E.: Formation of GFAP inclusions in astrocytes and their disaggregation by ?ß-crystallin. Am. J. Pathol., 154: 1563-1572 (1999).

• Levison, S.W.; Young, G.M.; and Goldman, J.E.: Cycling cells in the adult rat neocortex produce oligodendrocytes. J. Neurosci. Res., 57: 435-446 (1999).

• Kakita, A. and Goldman, J.E.: Patterns and dynamics of SVZ cell migration in the postnatal forebrain: monitering living progenitors in slice preparations. Neuron, 23: 461-472 (1999).

• Brenner, M., Johnson, A.B., Boespflug-Tanguy, O., Rodriguez, D., Goldman, J.E. and Messing, A. Mutations in glial fibrillary acidic protein (GFAP) associated with Alexander disease. Nature Genetics, 27: 117-120 (2001).

• Staugaitis, S.M., Zerlin, M., Levine, J.M., Hawkes, R., and Goldman, J.E.: Aldolase C/Zebrin II expression in neonatal rat forebrain reveals cellular heterogeneity within the subventricular zone and early astrocyte differentiation. J. Neurosci., 21: 6195-6205 (2001).