Research in the Lurie laboratory focuses on the glial response to central nervous system (CNS) injury and disease. Specifically, Lurie and her co-workers are interested in those cellular cascades which control the proliferation and migration of glial cells following damage, as well as those processes which regulate both the production of, and the glial response to, various growth factors. Recent work has centered on elucidating the role that tyrosine phosphorylation plays in these signal transduction events during CNS injury. These studies utilize a wide variety of model systems including the avian auditory system, rat hippocampus, mouse CNS, and several different tissue culture preparations. Techniques employed in the laboratory include non-radioactive enzyme activity assays, cell proliferation assays, polyclonal antibody development, tissue histology and immunocytochemistry, and image analysis.

Glial cells, particularly astrocytes, play a key role in CNS regeneration following damage. Individual responses of astrocytes are complex, varied, and are not well defined. Some subsets of astrocytes respond to injury by increased proliferation and other activities which are thought to inhibit neuronal regeneration. Other subsets may aid in regeneration by phagocytosis of cellular debris, reconstitution of the extracellular matrix, and secretion of growth factors. To date, it has been difficult to identify which population of astrocytes are involved in these various cellular activities. However, modulation of proliferation and other related cellular functions by external cues is often mediated by phosphorylation/dephosphorylation of intracellular proteins. This process is controlled by the competing activities of specific kinases and phosphatases, and protein tyrosine phosphorylation has been implicated in both the proliferation and differentiation of astrocytes.

Recent work in the Lurie laboratory has identified a subset of astrocytes in the chick auditory brainstem that show strongly increased immunostaining for the tyrosine phosphatase, SHP-1, following injury. This increase correlates with an increase in glial proliferation. Interestingly, the SHP-1 positive astrocytes appear to be those cells which do not enter the cell cycle, even though they are among the population which divide following injury. Similar responses have been found in the rat hippocampus following excitotoxic or metabolic-induced injury. These observations suggest that SHP-1 plays an important role in the regulation of cellular proliferation following CNS damage.

Other research in the group involves elucidating the role of SHP-1 during manipulation of both the cell cycle and growth factor-mediated signal transduction cascades in vitro, as well as the role this enzyme may play during the oncogenic transformation of astrocytes into malignant glial brain tumors. The Lurie lab maintains active collaborations with other research groups at the University of Washington, the University of Kansas Medical Center, and the Institute of Psychiatry, London.

Grass TM, Lurie DI, Coffin JD (2006)  Transitional angiogenesis and vascular remodeling during coronary angiogenesis in response to myocardial infarction.  In Press Acta Histochemica.

Beamer CA, Brooks DM, Lurie DI (2006)  Motheaten (me/me) mice deficient in SHP-1 are less susceptible to focal ischemia.  In press  J. Neurosci. Res. 

Zhao J, Brooks D, Lurie DI (2006) Lipopolysaccharide-activated  SHP-1 deficient motheaten microglia release increased nitric oxide, TNF-a and IL-1b, Glia 53(3):304-12. Lurie, Brooks, anGray (2006) The effect of Lead on the avian auditory brainstem. Neurotoxicology, 27(1):843-8.

Stone,  Lurie,  Kelley, and Poulsen (2005)  Adeno-Associated virus mediated gene transfer to hair cells and support cells of the cochlea.  Molecular Therapy, 11(6):843-848.

Zhao and Lurie (2004)  Loss of SHP-1 phosphatase selectively alters cytokine expression in the mouse hindbrain following cochlear ablation.   Cytokine, 28:1-9.

Zhao and Lurie (2004)  Cochlear Ablation in mice lacking SHP-1 results in an extended period of cell death in anteroventral cochlear nucleus neurons.  Hearing Res. 189:63-75.

Wishcamper, CA, Brooks DM,  Coffin JD, Lurie DI (2003) Focal ischemia upregulates SHP-1 in non-proliferating reactive astrocytes.  Brain Research, 974:88-98.

Sorbel, J.D. Brooks, D. M. and D.I. Lurie (2002) SHP-1 expressison in avian mixed neural/glial cultures.  J. of Neurosci. Res.  68:703-715.

Wishcamper, C.A., Coffin, J.D. and D.I. Lurie (2001)  Lack of the protein tyrosine phosphatase SHP-1 results in decreased numbers of glia within the Motheaten (me/me) mouse brain.  J. Comp. Neurol.  441:118-133.

Lurie, D.I., F. Solca, E.H. Fischer, E.W Rubel (2000) Tyrosine Phosphatase SHP-1 immunoreactivity increases in a subset of astrocytes following deafferentation of the chicken auditory brainstem.  J.Comp.Neurol.  421:199-214.

Lurie, D.I. and D. Durham (2000)  Neuronal death but not eighth nerve degeneration results in significant gliosis following deafferentation within the auditory brainstem nucleus, n. Magnocellularis in the adult chicken.   Hearing Research, 149: 189-198.

Kelley M.S. , D. I. Lurie, E. W Rubel (1997)  Rapid regulation of cytoskeletal proteins and their mRNAs following afferent deprivation in the avian cochlear nucleus.  J. Comp. Neurol. 389:469-483.

Lurie, D.I., T.R. Pasic, S.J. Hockfield, E.W Rubel (1997) Development of CAT-      301 immunoreactivity in Auditory brainstem nuclei of the gerbil.  J. Comp. Neurol.  380:319-334.

Oesterle, E.C., D.I.Lurie, E. W Rubel (1997)  Neurofilament proteins in avian auditory hair cells.  J. Comp. Neurol.  379:603-616.

Pijak S.D., G.F. Hall, P.J. Tenicki, A.S. Boulos, D.I. Lurie, M.E. Selzer. (1996) Neurofilament spacing, phosphorylation and axon diameter in regenerating and uninjured lamprey axons.  J. Comp. Neurol.  368:569-581.

Merrick, S.E., S.J. Pleasure, D.I. Lurie, D.S. Pijak, M.E. Selzer, V.M-Y. Lee (1995)  Glial cells of the lamprey central nervous system contain keratin.  J. Comp. Neurol. 355(2):199-210.

Lurie, D. I. and E.W Rubel (1994)  Unilateral cochlear removal results in increased astrocyte proliferation in the chick auditory nucleus, Nucleus Magnocellularis.  J. Comp. Neurol. 346:276-288.

Solca, F.F., D.I. Lurie, C.D. Diltz, R. Johnson, S. Kumar, K.A. Walsh, E.W Rubel, E.H. Fischer (1994) Identification and purification of NAP-185: a chicken brain neuroglia-associated protein. Journal of Biol. Chem. 269(44):27559-27565.

Garden, G.A., K.S. Canady, D.I. Lurie, M. Bothwell, E.W Rubel (1994)  A biphasic change in ribosomal conformation during deafferentation-induced neuronal death is altered by inhibition of mitochondrial, but not cytoplasmic, protein synthesis.   J. Neurosci. 14(4): 1994-2008.