Microglia, the immune cells of the central nervous system, undertake a number of different functional roles. One major role consists of participating in a signaling pathway that leads to excitatory neuronal death in acute (e.g., stroke), or chronic (e.g., Alzheimer's, amyotrophic lateral sclerosis, glaucoma) neurodegenerative diseases. We propose to investigate the process of microglial activation in this setting of excitotoxic neurodegeneration. Identification and characterization of genes involved in microglial activation could generate potential targets in the CNS for the rational design of new therapeutic approaches for intervention in these diseases. We propose to define, using DNA chip technology, the signaling cascades that result in microglial activation. Furthermore, we will make use of tissue plasminogen activator (tPA), a serine protease that is produced by neurons and microglia and that mediates microglial activation via interaction with a microglial cell surface receptor, annexin II. tPA will be used as a tool to dissect the process of activation, since it functions as an extracellular trigger to activate intracellular effectors. The signaling pathways that lead to microglial activation will be analyzed. This set of experiments will identify candidate targets for subsequent pharmaceutical study for inhibition or suppression of the neurotoxic properties of activated microglia.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Molecular, Cellular and Developmental Neurosciences 2 (MDCN)
Program Officer
Nunn, Michael
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
State University New York Stony Brook
Schools of Medicine
Stony Brook
United States
Zip Code
Miyauchi, Jeremy Tetsuo; Caponegro, Michael D; Chen, Danling et al. (2018) Deletion of Neuropilin 1 from Microglia or Bone Marrow-Derived Macrophages Slows Glioma Progression. Cancer Res 78:685-694
Miyauchi, Jeremy Tetsuo; Tsirka, Stella E (2018) Advances in immunotherapeutic research for glioma therapy. J Neurol 265:741-756
Powell, Jonathan; Mota, Filipa; Steadman, David et al. (2018) Small Molecule Neuropilin-1 Antagonists Combine Antiangiogenic and Antitumor Activity with Immune Modulation through Reduction of Transforming Growth Factor Beta (TGF?) Production in Regulatory T-Cells. J Med Chem 61:4135-4154
Nissen, Jillian C; Thompson, Kaitlyn K; West, Brian L et al. (2018) Csf1R inhibition attenuates experimental autoimmune encephalomyelitis and promotes recovery. Exp Neurol 307:24-36
Harrington, Andrea D; Schmidt, Millicent P; Szema, Anthony M et al. (2017) The Role of Iraqi Dust in Inducing Lung Injury in United States Soldiers-An Interdisciplinary Study. Geohealth 1:237-246
Nissen, Jillian C; Tsirka, Stella E (2016) Tuftsin-driven experimental autoimmune encephalomyelitis recovery requires neuropilin-1. Glia 64:923-36
Torres, Luisa; Danver, Joan; Ji, Kyungmin et al. (2016) Dynamic microglial modulation of spatial learning and social behavior. Brain Behav Immun 55:6-16
Miyauchi, Jeremy T; Chen, Danling; Choi, Matthew et al. (2016) Ablation of Neuropilin 1 from glioma-associated microglia and macrophages slows tumor progression. Oncotarget 7:9801-14
Lewis, Crystal S; Torres, Luisa; Miyauchi, Jeremy T et al. (2016) Absence of Cytotoxicity towards Microglia of Iron Oxide (?-Fe2O3) Nanorhombohedra. Toxicol Res (Camb) 5:836-847
Elmes, Matthew W; Kaczocha, Martin; Berger, William T et al. (2015) Fatty acid-binding proteins (FABPs) are intracellular carriers for ?9-tetrahydrocannabinol (THC) and cannabidiol (CBD). J Biol Chem 290:8711-21

Showing the most recent 10 out of 50 publications