Professor Goldman is working to understand environmental and lineage control of neuronal and glial fates in the developing CNS. Using viral gene transfer, transgenics, live slice imaging, and culture systems, his research is defining the migration of precursor cells from germinal zones of the perinatal rodent forebrain and cerebellum, and the development of these precursors into neurons and glia.. He is also interested in how these precursors can be altered to mimic the continued proliferation and migration seen in glial brain tumors. His laboratory also studies the population of cycling precursor cells in the adult CNS to understand their fates under normal and pathological situations. For example, cycling precursors in adult white matter can differentiate into myelinating oligodendrocytes after demyelination. The Goldman lab is studying Alexander disease, a degenerative disorder of white matter caused by mutations in the astrocyte intermediate filament protein, GFAP. They have found that mutant GFAP accumulation leads to upregulation of several cell stress pathways and alterations in astrocyte function that may cause the death of oligodendrocytes and neurons.
Mela and Goldman JE. The tetraspanin, KAI1/CD82, is expressed by late-lineage oligodendrocyte precursors and may function to restrict precursor migration and promote oligodendrocyte differentiation and myelination. J Neurosci, 29:11172-11181, 2009.
Tang G, Der Perng M, Wilk S, Quinlan R, and Goldman JE. Oligomers of mutant GFAP inhibit the proteasome system in Alexander disease astrocytes and the small heat shock protein, alpha B-crystallin, reverses the inhibition, J Biol Chem, 285: 10777-10785, 2010.
Ivkovic, S., Canoll, P., and Goldman, J.E. Constitutive EGFR signaling leads to glial progenitor hyperplasia in postnatal white matter. J. Neurosci., 28:914-922, 2008.
Tang G, Yue Z, Talloczy, Z, Hagemann T, Cho W, Sulzer D, Messing A, and Goldman JE: Alexander disease-mutant GFAP accumulation stimulates autophagy through p38 MAPK and mTOR signaling pathways. Hum Mol Genetics, 17:1540-1555, 2008.
Ventura R and Goldman JE: Dorsal radial glia generate olfactory bulb interneurons in the postnatal murine brain. J. Neurosci. 27:4297-4302, 2007.