Gender	Male
E-mail	gareth.john@mssm.edu

Research

Specific Clinical/Research Interests: CNS, glia, astrocyte, inflammation, injury, repair

Current Students: Blake Gurfein

Postdoctoral Fellows: Yueting Zhang, Azeb Tadesse Argaw, Andleeb Zameer

Research Personnel: Sean Mahase

Summary of Research Studies:
Injury, inflammation or degenerative disease in the central nervous system (CNS) is accompanied by alterations in the morphology and gene expression patterns of astrocytes, the most numerous population of CNS glia. This response is referred to as a reactive astrogliosis, and accumulating evidence suggests that these cells regulate the inflammatory reponse, and further that they represent a significant obstacle to CNS regeneration, both in terms of neurons and the oligodendrocytes that myelinate them. Our research focuses on understanding the molecular profile and functional significance of a reactive astrogliosis, with the ultimate goal of designing novel strategies to promote CNS repair. Core techniques in use in the laboratory include functional genomics, molecular and cellular biology, and confocal imaging.

John GR, Scemes E, Suadicani SO, Liu JS, Charles PC, Lee SC, Spray DC, Brosnan CF. IL-1beta differentially regulates calcium wave propagation between primary human fetal astrocytes via pathways involving P2 receptors and gap junction channels. Proc Natl Acad Sci U S A 1999 Sep 28; 96(20): 11613-11618.

Liu JS H, John GR, Sikora A, Hua LL, Lee SC, Brosnan CF. Modulation of interleukin-1beta and tumor necrosis factor alpha signaling by P2 purinergic receptors in human fetal astrocytes. J Neurosci 2000 Jul 15; 20(14): 5292-5299.

Duffy HS, John GR, Lee SC, Brosnan CF, Spray DC. Reciprocal regulation of the junctional proteins claudin-1 and connexin43 by interleukin-1beta in primary human fetal astrocytes. J Neurosci 2000 Dec 1; 20(23): RC114.

John GR, Simpson JE, Woodroofe MN, Lee SC, Brosnan CF. Extracellular nucleotides differentially regulate interleukin-1beta signaling in primary human astrocytes: implications for inflammatory gene expression. J Neurosci 2000 Jun 15; 21(12): 4134-4142.

John GR, Shankar SL, Shafit-Zagardo B, Massimi A, Lee SC, Raine CS, Brosnan CF. Multiple sclerosis: re-expression of a developmental pathway that restricts oligodendrocyte maturation. Nat Med 2002 Oct; 8(10): 1115-1121.

John GR, Chen LF, Rivieccio MA, Melendez-Vasquez CV, Hartley A, Brosnan CF. Interleukin-1beta induces a reactive astroglial phenotype via deactivation of the Rho GTPase-Rock axis. J Neurosci 2004 Mar 17; 24(11): 2837-2845.

Zhang Y, Taveggia C, Melendez-Vasquez C, Einheber S, Raine CS, Salzer JL, Brosnan CF, John GR. Interleukin-11 regulates oligodendrocyte survival and maturation, and myelin formation. J Neurosci 2006; 26: 12174-12185.

Argaw AT, Zhang Y, Snyder B, Zhao ML, Kopp N, Lee SC, Raine CS, Brosnan CF, John GR. Interleukin induces blood-brain barrier permeability via reactivation of the hypoxia-angiogenesis program. J Immunol 2006; 177: 5574-5584 .

Zhang Y, Raine CS, Brosnan CF, John GR. Interleukin-11: a survival and maturation factor for human oligodendrocytes. J Neurosci 2006; 26: 12174-12184.

Brosnan CF, John GR. Revisiting Notch in remyelination of multiple sclerosis lesions. J Clin Invest 2008; Epub ahead of print.

Argaw AR, Gurfein BT, Zhang Y, Zameer A, Brosnan CF, John GR. Downregulation of endothelial CLN-5 and OCLN is induced by VEGF-A, and correlates with blood-brain barrier permeability in the inflamed CNS. Proc Natl Acad Sci USA;.