Faculty / Research

Styliani-Anna E. Tsirka, PhD

Professor 

 

PhD, Biochemistry, Aristotle University of Thesssaloniki, Greece

B.S., Chemistry, Aristotle University of Thesssaloniki, Greece

631-444-3859  styliani-anna.tsirka@stonybrook.edu
Neuro-immune interactions: Cross-talk between the nervous and immune systems in health and disease

Traditionally the central nervous system (CNS) has been thought to be ‘immune privileged’ and not interact with the immune system. Increasing evidence however suggests that many neurodegenerative diseases, as well as many acute injuries in the CNS, are characterized by the presence of inflammatory cells in the CNS. An initial response to neuronal injury is evidenced by the activation of CNS microglia.  Microglia are antigen-presenting, immune-competent, macrophage-like cells that reside in the CNS and are able to modulate neuronal survival, or are hypothesized to affect neuronal structural changes occurring in response to neuronal activity. Our research interests concern the communication, signaling events and cell-cell interactions between neurons and microglia subsequent to normal or exaggerated stimulation of the CNS that lead to reorganization of neuronal connections in the brain or neuronal cell death.

Stella Tsirka was born and raised in Greece. She received her BS and PhD degrees from the University of Thessaloniki. She then pursued postdoctoral studies at Univ California San Francisco and SUNY Stony Brook, under the mentoring of Drs Phil Coffino and Sid Strickland, respectively. She was appointed Research Assistant Professor in the Department of Psychiatry at SBU in 1998, and joined the Pharmacology faculty in 2000.

Selected peer-reviewed publications or manuscripts in press.

1.    S.E. Tsirka, A. Gualandris, D.G. Amaral, S. Strickland (1995) Excitotoxin-induced neuronal degeneration and seizure are mediated by tissue-type plasminogen activator.  Nature 377:340-344.
2.    S.E. Tsirka, A.D. Rogove, S. Strickland (1996) Tissue plasminogen activator and neuronal cell death. Nature 384:123-124.
3.    S.E. Tsirka, T.H. Bugge, J.L. Degen, S. Strickland. Neuronal death in the CNS demonstrates a non-fibrin substrate for plasmin. (1997) Proc.Natl.Acad.Sci.USA 94: 9779-9781.
4.    A.D. Rogove, S.E. Tsirka. (1998) Neurotoxic responses by microglia elicited by excitotoxic injury in the mouse hippocampus. Curr.Biol.8: 19-25.
5.    Y.F. Wang, S.E. Tsirka, S. Strickland, P.E. Stieg, S.G. Soriano, S.A. Lipton. (1998) Tissue plasminogen activator (tPA) increases neuronal damage after focal cerebral ischemia in wild-type and tPA-deficient mice. Nature Med 4: 228-232.
6.    Y.-P. Wu, C.-J. Siao, W. Lu, T.-C. Sung, M.A. Frohman, P. Milev, T.H. Bugge, J.L. Degen, J.M. Levine, R.U. Margolis, S.E. Tsirka. (2000) The tPA/plasmin extracellular proteolytic system regulates hippocampal mossy fiber reorganization through a novel proteoglycan substrate. J. Cell Biol. 148:1295-1304
7.    W. Lu, M. Bhasin and S. E. Tsirka. (2002) Involvement of tissue plasminogen activator in both onset and effector phases of experimental allergic encephalomyelitis, J Neurosci: 22: 10781-10789.
8.    M Bhasin, M Wu, SE Tsirka. (2007) Modulation of microglial/macrophage activation by macrophage inhibitory factor (TKP) or tuftsin (TKPR) attenuates the disease course of experimental autoimmune encephalomyelitis, BMC Immunology, 8 (1): 10 [Epub ahead of print]
9.    W.B. Nolin, J. Emmetsberger, N. Bukhari, Y. Zhang, J.M. Levine, and S.E.Tsirka. (2008) tPA-Mediated Generation of Plasmin is Catalyzed by the Proteoglycan NG2, Glia,  56:177-189.
10.    Wu, M and SE Tsirka. (2009) Endothelial NOS-deficient Mice reveal dual roles for nitric oxide during Experimental Autoimmune Encephalomyelitis, Glia. 57(11):1204-15 PMCID: PMC2706940
11.    Pothakos, K, Robinson, JK, Marsteller, D., Gravanis, I, Dewey, SL., Tsirka SE. (2009) Decreased serotonin levels associated with behavioral disinhibition in tissue plasminogen activator deficient (tPA−/−) mice, Brain Research, 1326:135-42 PMCID: PMC2853966
12.    Mirrione MM, Konomos DK, Gravanis, I, Dewey, SL, Aguzzi, A, Heppner, FL, and SE Tsirka. (2010) Microglial ablation and lipopolysaccharide preconditioning affects pilocarpine-induced seizures in mice, Neurobiol Dis. 39(1):85-97 PMCID: PMC2875881
13.    Emmetsberger J, Mirrione MM, Zhou C, Siddiq M, Fernandez-Monreal M, Ji K, SE Tsirka (2010) Tissue Plasminogen Activator alters intracellular sequestration of zinc through interaction with the transporter ZIP4, J. Neurosci. 30(19):6538-47 PMCID: PMC2872103
14.    Yao Y, Tsirka SE. (2010) The C-terminus of mouse monocyte chemoattractant protein 1 (MCP1) mediates MCP1 dimerization while blocking its chemotactic potency. J Biol Chem. 285:31509-16. PMCID: PMC2951225
15.    Sierra A, Encinas JM, Deudero JJP, Chancey JH, Enikolopov G, Overstreet-Wadiche LS, Tsirka SE, Maletic-Savatic M (2010) Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Cell Stem Cell, 7:483-95
16.    Talos F, Abraham A, Vaseva A, Holembowski L, Tsirka SE, Scheel A, Bode D, Dobbelstein M, Bruck W, Moll UM (2010) p73 is an Essential Regulator of Neural Stem Cell Maintenance in Embryonal and Adult CNS Neurogenesis. Cell Death Diff, 17:1816-29
17.    Zhai H, Heppner FL, Tsirka SE (2011). Microglia/Macrophages Promote Glioma Progression, Glia. 59:472-85. PMCID: PMC3080032
18.    Yao Y and Tsirka, SE (2011) Truncation of Monocyte Chemoattractant Protein-1 by Plasmin Promotes Blood-Brain Barrier Disruption. J Cell Sci. 124:1486-95. PMCID: PMC3078815
19.    Yao Y, Tsirka SE. (2011) Mouse MCP1 C-terminus inhibits human MCP1-induced chemotaxis and BBB compromise. J Neurochem. 118:215-23
20.    Zhai H, Acharya S, Gravanis I, Mehmood S, Seidman RJ, Shroyer KR, Hajjar KA, Tsirka SE. (2011) Annexin A2 promotes glioma cell invasion and tumor progression. J Neurosci. 31:14346-60
21.    Bukhari N, Torres L, Robinson JK, Tsirka SE. (2011) Axonal regrowth after spinal cord injury via chondroitinase and the tissue plasminogen activator (tPA)/plasmin system. J Neurosci. 31(42):14931-43.
22.    Yao, Y and Tsirka SE (2012) The MCP1/CCL2-CCR2 system affects the progression and clearance of intracerebral hemorrhage. Glia 60(6):908-18
23.    Harrington AD, Tsirka SE, Schoonen MA. (2012) Quantification of particle-induced inflammatory stress response: a novel approach for toxicity testing of earth materials. Geochem Trans. 13(1):4. PMID:22513118
24.    Vaseva, AV, Holzmann, S, Ji, K, Tsirka, SE and Moll, UM (2012) p53 protein regulates the mitochondrial permeability transition pore during oxidative stress-induced necrosis and ischemic stroke. Cell, 149(7):1536-48
25.    Wu, M, Cypser, JH, Chen, E, Tsirka, SE (2012) Tuftsin promotes an anti-inflammatory switch and attenuates symptoms in Experimental Autoimmune Encephalomyelitis. PLoS One, 7(4):e34933. PMID: 22529957
26.    Emmetsberger J, Tsirka SE. (2012) Microglial inhibitory factor (MIF/TKP) mitigates secondary damage following spinal cord injury. Neurobiol Dis., 47(3):295-309. PMID: 22613732
27.    Ji J, Tsirka SE (2012) Inflammation Modulates Expression of Laminin in the CNS Following Ischemic Injury. J Neuroinflammation., 9:159.
28.    Louie E, Chen XF, Coomes A, Ji K, Tsirka S, Chen EI. (2012) Neurotrophin-3 modulates breast cancer cells and the microenvironment to promote the growth of breast cancer brain metastasis. Oncogene. 32(35):4064-77.
29.    Ji K, Akgul G, Wollmuth LP, Tsirka SE. (2013) Microglia actively regulate the number of functional synapses. PLoS One.8(2):e56293.
30.    Abraham AB, Bronstein R, Chen EI, Koller A, Ronfani L, Maletic-Savatic M, Tsirka SE. (2013) Members of the high mobility group B protein family are dynamically expressed in embryonic neural stem cells. Proteome Sci.11(1):18
31.    Bronstein R, Torres L, Nissen JC, Tsirka SE (2013) Culturing Microglia From The Neonatal And Adult Central Nervous System. JoVE, (78). doi: 10.3791/50647.
32.    Yao Y, Tsirka SE (2013) Blood-Brain Barrier and Monocyte Chemoattractant Protein-1. Cell Mol Life Sci., 71(4):683-97.
33.    Nissen JC, Selwood D, Tsirka SE (2013) Tuftsin signals through its receptor neuropilin-1 via the transforming growth factor beta pathway. J Neurochem, 127(3):394-402.
34.    Ji K, Miyauchi J, Tsirka SE (2013) Microglia: an active player in the regulation of synaptic activity. Neural Plasticity, 2013:627325
35.    Abraham AB, Bronstein R, Reddy AS, Maletic-Savatic M, Aguirre A, Tsirka SE. (2013) Aberrant Neural Stem Cell Proliferation and Increased Adult Neurogenesis in Mice Lacking Chromatin Protein HMGB2. PLoS One. 8(12):e84838.
36.    He Y, Yao Y, Tsirka SE, Cao Y. (2014) Cell-Culture Models of the Blood-Brain Barrier. Stroke. Jun 17. pii: STROKEAHA.114.005427. PMID: 24938839
37.    Yao Y and Tsirka SE (2014) Mouse Monocyte Chemoattractant Protein 1 (MCP1) Functions as a Monomer. Intern. J. Biochem Cell Biol,, in press
38.    Gao Z, Nissen JC, Ji K, Tsirka SE (2014) The experimental autoimmune encephalomyelitis disease course is modulated by nicotine and other cigarette smoke components. PLOS One, in press

Research Group

Jillian Nissen, Postdoc (jillian.cypser@stonybrook.edu)
Luisa Torres, PhD Graduate student (luisa.torres@stonybrook.edu)
Robert Bronstein, PhD Graduate student (robert.bronstein@stonybrook.edu)
Jeremy Miyauchi, PhD Graduate student (jeremy.miyauchi@stonybrook.edu)
Michael Caponegro, Master's graduate student
Billy (Hyun) Chun, Medical student
Toyosi Awotorebo, Undergraduate student
Ramyaprabha Bondalapati, Undergraduate student
Christopher Lopez, Undergraduate student
Petros Rafael, Undergraduate student

Stella Tsirka

Department of Pharmacological Sciences BST8, Rm 192 Stony Brook University 

Stony Brook, NY 11794-8651

Tel: 631-444-3859

Fax: 631-444-3218

Email: styliani-anna.tsirka@stonybrook.edu