Dr. Tiina M. Kauppinen
Assistant Professor - Department of Pharmacology and Therapeutics
University of Manitoba
753 McDermot Avenue, Chown Building A201, Winnipeg, MB R3E 0T6
tel: (204) 789-3846 fax: (204) 789-3932
email: tiina.kauppinen@med.umanitoba.ca

Research Focus:

My research centers on the role of neuroinflammation, particularly activation of microglia (brain macrophages/immune cells) and astrocytes/astroglia (brain support cells), on
neurological disorders. This interest stemmed from my Ph.D. thesis work (published under my maiden name, Tikka) in which we discovered the neuroprotective potential of minocycline, an antibiotic with several anti-inflammatory functions and one of the most promising treatments in ischemic stroke.

Neuroinflammation has been established as an important contributor in neurological conditions, including stroke, Alzheimer’s disease, multiple sclerosis and traumatic brain injury. In addition, a growing body of evidence suggests the presence of inflammatory component also in variety of psychiatric disorders such as depression and schizophrenia. Although activation of microglia and astroglia, and elevated levels of pro-inflammatory cytokines correlate with neuronal death, the cause-and-effect relationship between glial activation and neuronal damage is not clear. While glial release of pro-inflammatory cytokines, free radicals, and proteases can be detrimental to neurons, their ability to phagocyte (microglia), support neuronal metabolism (astroglia) and release of trophic factors and antioxidants can be beneficial for repair and recovery process.

The focus of my research is: 1) to understand how neuroinflammatory cells (microglia, astroglia and circulating peripheral cells) are involved in neurodegeneration and neurogenesis; 2) to learn to modulate their responses towards neuroprotective phenotype; and 3) to develop new therapeutic strategies with multiple disease relevance.

My laboratory is currently developing approaches to directly and exclusively target microglial cells, which will allow us to directly address their role in neuroinflammation and nervous system disorders. In our studies we employ in vitro and in vivo approaches, such as functional genomics, cell-specific gene delivery, imaging techniques and behavioural tests.

Selected Publications:

Kauppinen TM, Suh SW, Higashi Y, Berman AR, Escarten C, Won SJ, Wang C, Cho SH, Gan L and Swanson RA. Poly(ADP-ribose)polymerase-1 modulates microglial responses to amyloid β. J. Neuroinflam. 2011; 8:152.

Cho SH, Sun B, Zhou Y, Kauppinen TM, Halabisky B, Wes P, Ransohoff RM, Gan L. CX3CR1 modulates microglial activation and protects against plaque-independent cognitive deficits in a mouse model of Alzheimer's disease. J. Biol. Chem. 2011; 286(37):32713-3222.

Kauppinen TM, SW Suh SW, Berman A, Hamby A, Swanson RA. Inhibition of poly(ADP-ribose)-polymerase suppress inflammation and promotes recovery after ischemia injury. J. Cereb. Blood Flow Metab. 2009; 29(4):820-829.

Burns, DM, Ying W, Kauppinen TM, Zhu K, Swanson RA. Selective Down-Regulation of Nuclear Poly(ADP-Ribose) Glycohydrolase. PLoS ONE. 2009; 4(3):e4896.

Brennan AM, Suh SW, Won SJ, Narasimhan P, Kauppinen TM, Lee H, Edling Y, Chan PH, Swanson RA.NADPH oxidase is the primary source of superoxide induced by NMDA receptor activation. Nat. Neurosci. 2009; 12(7):857-863.

Kauppinen TM, Higashi Y, Suh SW, Escartin C, Nagasawa K, Swanson RA.Zinc triggers microglial activation. J. Neurosci. 2008; 28(22):5827-5835.

Kauppinen TM, Chan WY, Suh SW, Wiggins AK, Huang EJ and Swanson RA. Direct phosphorylation and regulation of poly(ADP-ribose) polymerase-1 by extracellular signal-regulated proteins 1/2. Proc. Natl. Acad. Sci. U S A. 2006; 103(18): 7136-7141.

Alano CC, Kauppinen TM, Vall AV, Swanson RA. Minocycline inhibits poly(ADP-ribose) polymerase-1 at nanomolar concentrations. Proc. Natl. Acad. Sci. U S A. 2006; 103(25):9685-90.

Kauppinen TM, Suh SW, Genain CP, Swanson RA.Poly(ADP-ribose) polymerase-1 activation in a primate model of multiple sclerosis. J. Neurosci. Res. 2005, 81(2):190-198

Kauppinen TM, Swanson RA. Poly(ADP-ribose)polymerase-1 promotes microglial activation, proliferation, and matrix metalloproteinase-9 - mediated neuron death. J. Immunology. 2005; 174: 2288-2296.

Tikka TM, Fiebich BL, Goldsteins G, Keinanen R, Koistinaho J. Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia. J. Neurosci. 2001; 21(8):2580-2588.

Yrjanheikki J, Tikka T, Keinanen R, Goldsteins G, Chan PH, Koistinaho J A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc. Natl. Acad. Sci. U S A. 1999; 96(23):13496-13500.