Glenn K. Matsushima, Ph.D.

gkmats@med.unc.edu 7109D Neuroscience Research Building Campus Box 7250 Chapel Hill, NC 27599-7250 919.966.0408

Research

Our laboratory is interested primarily in the responses of macrophages during injury to the central nervous system and during inflammation after insult by bacterial pathogens. We use molecular, cellular and biochemical approaches both in vitro and in vivo to identify the function of key mediators during pathogenesis.

Inflammation: One major area of research is to study the regulation of immune cells during bacterial infection and identify molecules important in regulating inflammation. We have focused on the function of a novel set of receptors known as Mer/Axl/Tyro3 receptor tyrosine kinases. Mer is expressed on macrophages; however, only recently have possible functions been elucidated. We find that Mer is important in the clearance of apoptotic cells and the failure to do so results in autoimmune disease such as systemic lupus erythematosus. We believe that this process may alter antigen presentation and appears important in the down regulation of inflammation, particularly TLR4-mediated activation of macrophages and dendritic cells.. Furthermore, this receptor may be key to understanding certain heritable forms of retinitis pigmentosum which leads to blindness.

Neuroimmunology: One major area of research is role of immune cells, particularly microglia that are resident macrophages of the brain, during demyelinating disease. We use murine models of demyelination to assess the role of receptors, cytokines, growth factors and chemokines. One model of demyelination that is induced by exposure to a copper chelator, cuprizone, in which there is a perturbation in the oligodendrocyte population that results in demyelination and microglia/macrophage accumulation. This model is very useful in that remyelination can also be studied and events similar to multiple sclerosis are featured. Thus, our hopes are to identify novel molecules, some of which are produced by microglia/macrophages, which may be therapeutically important in ameliorating central nervous system disease.

Publications

Williams JC, Wagner NJ, Earp HS, Vilen BJ, Matsushima GK (2010). Increased hematopoietic cells in the mertk-/- mouse peritoneal cavity: a result of augmented migration. J Immunol. 184(12):6637-48.

Seitz HM, Matsushima GK (2010). Dendritic cells in systemic lupus erythematosus. Int Rev Immunol. 29(2):184-209. Review.

Taylor LC, Puranam K, Gilmore W, Ting JP, Matsushima GK (2010). 17beta-estradiol protects male mice from cuprizone-induced demyelination and oligodendrocyte loss. Neurobiol Dis. 39(2):127-37.

Taylor LC, Gilmore W, Ting JP, Matsushima GK (2010). Cuprizone induces similar demyelination in male and female C57BL/6 mice and results in disruption of the estrous cycle. J Neurosci Res. 88(2):391-402.

Williams JC, Craven RR, Earp HS, Kawula TH, Matsushima GK (2009). TAM receptors are dispensable in the phagocytosis and killing of bacteria. Cell Immunol. 259(2):128-34.

Taylor LC, Gilmore W, Matsushima GK (2009). SJL mice exposed to cuprizone intoxication reveal strain and gender pattern differences in demyelination. Brain Pathol. 19(3):467-79.

Hiremath MM, Chen VS, Suzuki K, Ting JP, Matsushima GK (2008). MHC class II exacerbates demyelination in vivo independently of T cells. J Neuroimmunol. 203(1):23-32.

Seitz HM, Camenisch TD, Lemke G, Earp HS, Matsushima GK (2007). Macrophages and dendritic cells use different Axl/Mertk/Tyro3 receptors in clearance of apoptotic cells. J Immunol. 178(9):5635-42.

Angelillo-Scherrer A, Burnier L, Flores N, Savi P, DeMol M, Schaeffer P, Herbert JM, Lemke G, Goff SP, Matsushima GK, Earp HS, Vesin C, Hoylaerts MF, Plaisance S, Collen D, Conway EM, Wehrle-Haller B, Carmeliet P (2005). Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy. J Clin Invest. 115(2):237-46.

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Affiliations

Department of Microbiology & Immunology
Program in Molecular Biology & Biotechnology
Neuroscience Center
Comprehensive Center for Inflammatory Disorders
Neurodevelopmental Disorders Research Center
Curriculum in Neurobiology
Curriculum in Oral Biology