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Principal Investigator/Program Director (Last, First, Middle): Halonen, Sandra K. BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES. NAME POSITION TITLE Sandra K. Halonen Associate Professor eRA COMMONS USER NAME SHALONEN EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) DEGREE INSTITUTION AND LOCATION (if YEAR(s) FIELD OF STUDY applicable) University of Illinois, Champaign-Urbana, IL. B.S. 1976-1980 Biology M.S. University of Illinois, Champaign-Urbana, IL. 1982-1984 Evolutionary Ecology Champaign-Urbana. M.S. Ph.D. Louisiana University, Baton Rouge, LA. 1989-1993 UniversityState of Illinois, Champaign-Urbana. IL. 1982-1984 Parasitology Evolutionary Ecology A. Personal Statement University of Illinois, Champaign-Urbana. IL. 1982-1984 Louisiana State University, Baton Rouge, LA. 1989-1993 Parasitology My research is focused on understanding the role of astrocytes in the intracerebral immune response to Louisiana State University, Baton Rouge, LA. 1989-1993 T. gondii in latent infections in immunocompetant hosts and in reactivated Toxoplasmosis in immunosuppressed individuals. Recently my research has begun to define the functional impact of the parasite in neurons and to investigate chronic Cerebral Toxoplasmosis and development of neuropsychiatric disorders such as Schizophrenia. B. Positions and Honors Positions and Employment 1994-1997 Aaron Diamond Post Doctoral Research Fellow, Dept. of Neurology, Albert Einstein College of Medicine, Bronx, NY 1997-1998 Research Associate, Dept. of Pathology, Albert Einstein College of Medicine, Bronx, NY 1998-2003 Assistant Professor, Dept. of Natural Sciences, Mercy College, Dobbs Ferry, NY 1998-present Visiting Assistant Professor, Dept. of Pathology; Albert Einstein Coll. of Medicine, Bronx, NY 2003-present Affiliate Assistant Professor, Dept. of Microbiology, University of Washington, Seattle, WA 2003-2009 Assistant Professor, Dept. of Microbiology, Montana State University, Bozeman, MT 2010-present Associate Professor, Dept. of Microbiology and Immunology, Montana State University, Bozeman, MT Honors 1989-93 LSU Alumni Federation Fellowship 1994-97 Aaron Diamond Postdoctoral Fellowship, Albert Einstein College of Medicine; Bronx, N.Y. 2001 Sr. Gratia Mahia Award for Excellence in Teaching, Mercy College, Dobbs Ferry NY 2008 Lucy Logan Research Award; Montana State University, Bozeman, MT. 2007-09 External Advisory Committee Member, NIH-Fogarty Global Infectious Disease Training Grant; Albert Einstein College of Medicine; Bronx, N.Y 2011-present Associate Editor for Journal of Neuroinfectious Diseases PHS 398/2590 (Rev. 09/04) Page 1 Biographical Sketch Format Page Principal Investigator/Program Director (Last, First, Middle): Halonen, S.K. C. Peer-Reviewed Publications (in chronological order) Weidner, E. and S.K. Halonen. 1993. Microsporidian spore envelope keratins phosphorylate and disassemble during spore activation. J. Euk. Microbiol. 40:783-788. Halonen, S.K. and E.Weidner. 1994. Overcoating of Toxoplasma parasitophorous vacuoles with host cell vimentin type intermediate filaments. J. Euk. Microbiol. 41:65-71. Weidner, E., S.B. Manale, S.K. Halonen, and J.D. Lynn. 1994. Microsporidian spore invasion tubes as revealed by fluorescent probles. Biol. Bull. 187:255-6. Weidner, E., S.B. Manale, S.K. Halonen, and J.D. Lynn. 1995. Protein-membrane interaction is essential to normal assembly of the microsporidian spore invasion tube. Biol Bull. 188: 128-135. Halonen, S.K., E. Weidner and J.F. Siebenaller. 1996. Evidence for heterotrimeric GTP-binding proteins in Toxoplasma gondii. J. Euk. Microbiol. 43:187-192. Halonen, S.K., W.D. Lyman and F.C. Chiu. 1997. Growth and development of Toxoplasma gondii in a human neurons and astrocytes. J. Neuropath. Exp. Neurology 55:1150-56. Halonen, S.K., F.C. Chiu and L.M. Weiss. 1998. Association of host cell intermediate filaments with Toxoplasma gondii cysts in murine astrocytes. Int. J. Parasitology 28:815-823. Halonen, S.K., F.C. Chiu and L.M. Weiss. 1998. Effect of cytokines on the growth of Toxoplasma in murine astrocytes. Infect. Immun. 66:4989-4993. Ma Y.F., Y.W. Zhang, S.K. Halonen, M.M. McAllister, and L.M. Weiss. 1999. The in vitro development of Neospora caninum bradyzoites. Int J. Parasitol. 10:1713-23. Halonen, S.K. & L.M. Weiss. 1999. Effect of cytokines and quercetin on Toxoplasma gondii cyst induction in murine astrocytes. J. Euk. Microbiol. 46(5):83S-84S. Halonen, S.K. and L.M. Weiss. 2000. Investigation into the mechanism of IFN-γ mediated inhibition of Toxoplasma gondii in murine astrocytes. Infect. Immun. 68:3426-3430. Huang, H., S.B. Petkova, R.G. Pestell, B. Bouzahzah, J. Chan, H. Magazine, L.M. Weiss, G.J. Christ, P. Lisanti, S.A. Douglas, V. Shtutin, S.K. Halonen, M. Wittner and H.B. Tanowitz. 2000.Trypanosoma cruzi infection (Chagas’ disease) of mice causes activation of the mitogen-activated protein kinase cascade and expression of endothelin-1 in the myocardium. J. Cardiovasc. Pharmacol. 36:S148-50. Zhang, Y.W., S.K. Halonen, Y.F. Ma, M. Wittner and L.M. Weiss. 2001. Initial characterization of CST, a Toxoplasma gondii cyst wall glycoprotein. Infect. & Immun. 69:501-507. Halonen, S.K. and L.M. Weiss. 2001. Interferon gamma induced inhibition of Toxoplasma gondii is mediated by IGTP. Infect. Immun. 69: 5573-6. Halonen, S.K. 2004. World Class Parasites Vol. 8: Opportunistic Infections: Toxoplasma, Sarcocystis, Microsporidia. Chapter 5. Immune response to Toxoplasma gondii in the central nervous system. David S. Lindsey and Louis M. Weiss Editors. Kluwer Academic Publishers; pp 67-88. Suzuki, Y. and S.K. Halonen. 2006. Cerebral Toxoplasmosis: Pathogenesis and Host Resistance. In: Toxoplasma gondii - a Model Apicomplexan; Perspectives and Methods. Kami Kim and L.M. Weiss, Eds; Elsevier Press Halonen, S.K., T. Woods, K. McInnerney, and L.M. Weiss. 2006. Microarray Analysis of the IFNγ response genes in Astrocytes. J. Neuroimmunology 175:19-30. Dzierszinski, F., M., M. Pepper, J.S. Stumhofer, D.F. LaRosa, E. H. Wilson, L.A. Turka, S.K. Halonen, C.A., Hunter, and D.S. Roos. 2007. Presentation of Toxoplasma gondii antigens via the endogenous major histocompatibility complex Class I pathway in non-professional and professional antigen presenting cells. J. Immunol. 75 (11): 5200-9. Halonen, S.K. and L.M. Weiss. 2008. Toxoplasma gondii IWOP10 2008: One Hundred Years and Counting. Submitted to J. Eukaryotic Microbiology July 2008; invited submission Melzer, T.A., A. Duffy, L.M. Weiss and S.K. Halonen. 2008. IGTP is necessary for Toxoplasma Vacuolar Disruption and Induces Parasite Egression in IFNγ Stimulated Astrocytes; Infection and Immunity 76(11):4883-4894. Halonen, S.K. 2009. Role of Autophagy in the Host Defense against Toxoplasma gondii in Astrocytes. Autophagy 5(8):268-269. PHS 398/2590 (Rev. 09/04) Page Continuation Format Page Principal Investigator/Program Director (Last, First, Middle): Halonen, S.K. Halonen, S.K., T.C. Melzer, H.J. Cranston, and L.M. Weiss. 2010. Host Cell Preference of Toxoplasma gondii in Murine Brain: A confocal study. Journal of Neuroparasitology; June 2010. Zhang, Y.W., S.K. Halonen, Y.F. Ma, H.B. Tanowitz and L.M. Weiss. 2010. A Purification Method for Enrichment of the Toxoplasma gondii Cyst Wall. J. Neuroparasitology. Halonen, S.K. and L.M. Weiss. 2013. Toxoplasmosis; Handbook of Clinical Neurology, Volume 114 (3rd Series); Neuroparasitology and Tropical Neurology; pgs. Elsevier Science. Y. Suzuki, O. Sa, E. Ochai, J. Mullins, R. Yolken, and S. Halonen. 2013. Cerebral Toxoplasmosis: Pathogenesis, Host Resistance and Behavioral Consequences In: Toxoplasma gondii - a Model Apicomplexan; Perspectives and Methods; p. 751 – 783; Second Edition. Kami Kim and L.M. Weiss, Elsevier Press. S.K. Halonen., Melzer, T.A. H.J. Cranston, J. Gress, K. McInnerney, A. Mazurie, and E. Dratz. 2014. Differential gene expression in murine astrocytes infected with virulent (type I) vs. avirulent (type II) strains of Toxoplasma gondii. 2014. Journal of Neuroinfectious Diseases 5(2). S.K.Halonen. Modulation of Host Programmed Cell Death Pathways by the Intracellular Protozoan Parasite, Toxoplasma gondii: implications for maintenance of chronic infection and potential therapeutic applications; Manuscript accepted for publication in Book entitled “Cell Death – Autophagy, Necrosis and Apoptosis”; anticipated publication date: May 2015 Tanaka, N., H.J. Cranston, W. Maaty, B. Bothner and S.K. Halonen. Proteomic Host Response to Toxoplasma gondii strains of distinct virulence phenotypes. Manuscript in Preparation. D. Research Support Completed Research Grants: IFNγ Inhibition of Toxoplasma gondii in Astrocytes P.I.: Sandra K. Halonen Agency: National Institute of Allergy & Infectious Disease Type: R21 AI64057-01 Funding Period: 3/14/05 – 3/15/07 Major Goal: To investigate the mechanism of IFNγ inhibition of Toxoplasma gondii in astrocytes. IFNγ Immune Effector Mechanisms in Cerebral Toxoplasmosis P.I.: Sandra K. Halonen Agency: National Institute of Allergy & Infectious Disease Type: R21 AI64652-01 Funding Period: 3/14/05- 3/14/08 Major Goal: To investigate the mechanism of IGTP-dependent IFNγ induced inhibition of Toxoplasma gondii in astrocyte Toxoplasma gondii and Schizophrenia: Pilot Study P.I.: Sandra K. Halonen Agency: Stanley Medical Research Institute Funding Period: 3/01/08 - 2/28/11 Major Goal: To investigate the possible role of infection with Toxoplasma gondii and Schizophrenia via RT-PCR and immunohistochemistry using human brain tissues of schizophrenia positive patients. Global Analysis of the Host Cell Response to Infection with Toxoplasma gondii in Astrocytes P.I.: Edward Dratz; Project P.I.: S.K. Halonen Agency: National Institute of Health Type: COBRE (P-30) Funding Period: 9/26/08 – 2/28/14 Major Goal: To define the IFNγ response to Toxoplasma gondii infection in astrocytes at the transcriptional and proteomic levels. PHS 398/2590 (Rev. 09/04) Page Continuation Format Page Principal Investigator/Program Director (Last, First, Middle): Halonen, S.K. Grants Funded: Neural Stem Cells and 3D Culture Models P.I.: Sandra K. Halonen Agency: Gulf Manco Group Co. Type: Fellowship Award Funding Period: 09/01/14-05/15/18 Major Goal: Neural Stem Cells (NSCs) are partially differentiated pluripotent stem cells that have the ability to generate all types of cells found in the central nervous system (CNS). NSCs derived differentiated cells will be used to generate cerebral organoid cultures, 3-D brain-like masses, created in vitro. The cerebral organoids created by these studies will be used to model Cerebral Toxoplasmosis and other disease processes in the CNS. Grants Submitted (pending): Toxoplasma gondii and the Nervous System P.I.: Louis M. Weiss; Consortium Investigator: S.K. Halonen Agency: NIH-NIAID Type: R01 (Submitted 06/05/14, not funded; resubmission in consideration) Funding Period: April 2016-March 2020 Major Goal: The effect of T. gondii infection will be examined using imaging mass spectrometry to examine small molecule profiles surrounding T. gondii cysts in mouse brains with latent infection. Ultrastructural and SeeDB approaches will be used to characterize the distribution and formation of T. gondii tissue cysts. Grants in Preparation: Proteomic Analyses of Astrocyte Host Cell Responses to Toxoplasma gondii strains of Distinct Virulence Phenotypes P.I.: Sandra K. Halonen Agency: NIH-NIAID Type: R21 (Anticipated Submission Date: 06/16/15) Funding Period: 12/1/15 -11/30/17 Major Goal: To identify astrocyte host cell proteins and host targets of parasites kinases and phosphatases that are differentially regulated during parasite infection and explore how these host cell changes are altered by the parasites of distinct virulent phenotypes. Model of Cerebral Toxoplasmosis in Human Neuronal Cells P.I.: Sandra K. Halonen Agency: NIH-NIMH Type: R01 (Anticipated Submission Date: 10/05/15) Funding Period: 4/1/16-3/30/20 Major Goal: Human neurons and astrocytes, derived from ihPSC’s will be used to model Cerebral Toxoplasmosis to further our understanding of chronic Toxoplasma infection in the immunocompetant host and its possible etiological role in psychiatric disorders such as Schizophrenia. Transcriptional, proteomic and cellular assays incorporating optogenetic approaches, will be used to assess functional impact of the parasite on neuronal functions. PHS 398/2590 (Rev. 09/04) Page Continuation Format Page