Christine A. Kirvan
Department of Biological Sciences
California State University Sacramento
(916) 278-6438
ckirvan@csus.edu
EDUCATION
Ph.D., Microbiology (emphasis Immunopathology). University of California, Davis.
April 2000. G.P.A. 3.9. Dissertation title: The role of complement activation in experimental autoimmune myasthenia gravis using recombinant anti-acetylcholine receptor monoclonal antibodies.
Advisors: Mark Agius, M.D. and Robert Fairclough, Ph.D.
Master of Science, Microbiology . University of California, Davis, May 1997
Bachelor of Science, Microbiology . California State University, Fresno, May 1991
G.P.A. 3.65. Cum Laude
TEACHING EXPERIENCE
Associate Professor, California State University, Sacramento, Sacramento, CA.
2003-present. Upper division microbiology lecture and laboratory (BIO 139).
Immunology lecture (BIO 149A). Immunology and serology laboratory (BIO 149B).
Cell Physiology (BIO 121).
Co-Instructor, University of Oklahoma, Oklahoma City, OK. 2002-2003
Special Studies in Immunology
Adjunct Part-time/Full-time faculty, American River College, Sacramento, CA. 1998-
1999. Instructor for Microbiology, lecture and laboratory.
RESEARCH EXPERIENCE
Associate Professor, California State University, Sacramento, 8/03-present. The laboratory is currently investigation mechanisms of antibody-mediated pathogenesis in
Sydenham’s chorea, a pediatric, post-streptococcal autoimmune disorder. We are also investigating the role of streptococcal infections in a group of related neurological disorders known as PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders
Associated with Streptococcus) that include obsessive-compulsive disorder, pediatric tic disorder, and forms of attention deficit/hyperactivity disorder. There are many immunological similarities between Sydenham’s chorea and the PANDAS group of disorders suggesting that group A streptococcal-induced neurological disease may be
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more prevalent than previously thought. There are three areas of active research in my laboratory.
Expression of human brain cDNA by phage display for the identification of molecular targets in autoimmune neurological disorders.
The project will identify specific cell surface proteins in brain recognized by pathogenic antibodies in Sydenham’s chorea and PANDAS. The identification of specific proteins in the brain will better elucidate the mechanisms of pathogenesis of these disorders and will provide clues into the neurological consequences of antibody deposition in the brain.
Chorea- and PANDAS-specific cell surface proteins may potentially be used as targets for therapeutic. The data produced by the study may yield insights into these perplexing neurologic and psychiatric disorders that affect children in Sacramento and throughout the world.
Identification of antibody-mediated disruptions of neurotransmitter pathways in
Sydenham's chorea.
We are investigating the ability of chorea-specific monoclonal and patient-derived antibodies to deregulate the synthesis and release of the neurotransmitters dopamine and serotonin. Levels of tyrosine hydroxylase and tryptophan hydroxylase are investigated using immunoshitochemistry in the SK-N-SH human neuroblastoma in vitro model and the Lewis rat in vivo model.
Streptococcal M protein epitope mapping for Pediatric Autoimmune Neuropsychiatric
Disorders Associated with Streptococcus (PANDAS)
The project will identify group A streptococcal reactivity of PANDAS and non-PANDAS serum antibody. Using synthetic overlapping peptides of the M protein, the specific epitopes that are involved in PANDAS pathogenesis can be identified. Both ELISA and immunohistochemistry methods are employed for this study. Isolation of an immunodominant epitope will allow for the identification of the human cross-reactive autoantigen.
Rheumatic heart disease: identifications of autoimmune mechanisms of cardiac damage
The project with focus on rheumatic heart disease mediated by passive transfer of
Streptococcus pyogenes -specific T cells: studies in T cell infiltration of heart tissues and upregulation of endothelial cell adhesion molecules. We will also study antibody subclass distribution in rheumatic heart disease and Sydenham’s chorea:
Postdoctoral Fellowship , University of Oklahoma Health Sciences Center, 5/00-7/03.
Production, characterization, and analysis of monoclonal antibodies from patients with
Streptococcus pyogenes -induced rheumatic heart disease and Sydenham’s chorea. Antistreptococcal monoclonal antibodies (mAbs) derived from a patient with rheumatic carditis and Sydenham’s chorea were selected by cross-reactivity with group A streptococcal membrane and the dominant group A carbohydrate epitope N-acetyl-

-Dglucosamine by ELISA analysis. To identify molecular targets in brain tissue, mAbs were reacted with immunoblots of emulsified mouse brain extracts separated by SDS-
PAGE. The mAbs recognized a 55kD brain protein revealed by N-terminal sequencing
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to corresponded to

-tubulin by genetic database alignment. mAb specificity to tubulin was confirmed by both ELISA and immunoblot against purified brain tubulin. In addition to tubulin, the mAbs were found to recognize ganglioside antigens in ELISA.
This finding is of particular interest as gangliosides and tubulin associate at the cell membrane. The mAbs were not found capable of directing complement-mediated lysis or apoptosis of the neuronal cell line. The mAbs labeled human basal ganglia tissue and formaldehyde-fixed neuroblastoma cells indicating that mAb binding may influence cell physiology through aberrant signal transduction. The mAbs and patient sera were subsequently shown to modulate the activation of calcium/calmodulin dependent protein kinase (CaM II) by 32 P assay and evoke dopamine release from human neuroblastoma cells. Tubulin and/or gangliosides may play an important role as tissue targets for autoantibodies in brain disorders such as Sydeham’s chorea.
Graduate Study , University of California, Davis, 7/92-9/98 .
Complement-mediated pathogenesis in experimental autoimmune myasthenia gravis
(EAMG) in Lewis rats. This project has involved the construction of class switch mutant recombinant antibodies in which the variable region of a myasthenia-producing antibody has been joined to non-complement activating Fc fragments, in addition to the construction of a wild-type 132A. The variable regions of both heavy and light chains were rescued utilizing 5’ RACE and 32
P-based sequencing. These antibodies have been used to study the levels of complement-induced destruction of the acetylcholine receptor and neuromuscular junction in vivo and in vitro and are compared to wild-type myasthenia-producing antibodies. Assessment of complement activation was analyzed by 51 Cr-rlease assay and the non-complement activating anti-AChR antibody will be given to Lewis rats with active EAMG in an attempt to block or reduce the level of clinical disease. Antibodies capable of blocking the active disease state will be humanized for use as this work may lead to a possible development of an immunotherapy for EAMG and has application for the human disease, 1992-1998.
Isolation and characterization of genomic heavy chain varible region of the derived
132A and YTH 34.5 heavy chain variable regions. Genomic DNA from rat glial tumor cell line was used to PCR amplify the VH which encodes both the 132A and YTH34.5 heavy chain variable region. The sequence of the genomic VH was compared to the VH sequences of 132A VH(anti-AchR mAb) and YTH34.5(anti-CD52 mAb).
Detection of serum antibodies to a novel antigen in multiple sclerosis and other neurological diseases. This research involved the screening of 140 patients and normal controls for serum antibodies to a-crystallin. This protein was injected into Lewis rats and induced an EAE-like syndrome. This project involved ELISA and western blot, animal model, and hybridoma technology, 1996-1997.
Undergraduate Research , California State University, Fresno, 1989-1991
Evolution of RNA splicing, specifically on the possible existence of small nuclear ribonucleoprotein (snRNP) particles in Bacillus subtilis . This investigation utilized both autoimmune rheumatoid patient sera and a snRNP-specific monoclonal antibody to identify six snRNP-like RNAs in 32 P-labeled B. subtilis extracts using immunoprecipitation, Urea-PAGE, and autoradiography procedures.
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PUBLICATIONS
Kirvan, CA . JG Galvin, S Kosanke, and MW Cunningham. “Streptococcal M-Protein
Specific T Cell Lines From Experimental Autoimmune Valvulitis: Identification of
Cardio-pathogenic Epitopes”. To be submitted to Journal of Clinical Investigation
Manuscript in progress.
Kirvan, CA
, H. Hill, G. Veasy, EE Adderson, and MW Cunningham. “Insights Into the
Immunology of Acute Rheumatic Fever: A Study of Antibody Subclass Distribution and the TH1/TH2 Paradigm”. To be submitted to the Journal of Infectious Diseases 4/15/09.
Manuscript in progress.
Kirvan, CA , CJ Cox, SE Swedo, and MW Cunningham. Tubulin Is a Neuronal Target of Autoantibodies in Sydenham's Chorea. J. Immunology , 2007 June 1;178(11):7412-21.
Kirvan, CA , SE Swedo, LA Snider, and MW Cunningham. Antibody-Mediated
Neuronal Cell Signaling Links Pediatric Autoimmune Neuropsychiatric Disorders
Associated with Streptococcus (PANDAS) with Sydenham’s Chorea.
J. Neuroimmunology, 2006 Oct;179(1-2):173-9
Kirvan, CA , SE Swedo, D Kurahara, and MW Cunningham. Streptococcal Mimicry and
Antibody-Mediated Pathogenesis in Sydenham’s Chorea. Autoimmunity , 2006
Feb;39(1):21-9
Kirvan, CA , SE Swedo, JS Heuser, and MW Cunningham. Mimicry and Autoantibody-
Mediated Neuronal Cell Signaling by Calcium/Calmodulin-Dependent Protein Kinase II in Sydenham’s Chorea.
Nature Medicine , 2003 Jul;9(7):914-20.
Agius, MA, CA Kirvan , AL Schafer, E Gudapati, and S Zhu. High prevalence of antialpha-crystallin antibodies in multiple sclerosis: correlation with severity and activity of disease. Acta Neurol Scand. 1999 Sep; 100 (3):139-47.
Agius, MA, S Zhu, EK Lee, JA Aarli, CA Kirvan , RH Fairclough, and R Masselli.
Antibodies to AChR, synapse-organizing proteins, titin, and other muscle proteins in
Morvan's fibrillary chorea. Ann N Y Acad Sci. 1998 May 13; 841 :522-4.
Agius, MA, S Zhu, CA Kirvan , AL, Schafer, MY Lin, RH Fairclough, JJ Oger, T Aziz, and JA Aarli. Rapsyn antibodies in myasthenia gravis. Ann N Y Acad Sci. 1998 May
13; 841 :516-21.
Agius, MA, CA Kirvan , and B Sanyal. Homology of an anti-acetylcholine receptor monoclonal antibody with a monoclonal antibody to Campath-1 antigen suggests usage of the same VH genes. Ann N Y Acad Sci. 1998 May 13; 841 :469-70.
Kirvan , CA , S. Zhu, DP Richman, and MA Agius. Expression and initial characterization of recombinant antiacetylcholine receptor antibodies in experimental
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autoimmune myasthenia gravis. Ann N Y Acad Sci. 1998 May 13; 841 :466-8.
Richman, DP, MA Agius, CA Kirvan , CM Gomez, RH Fairclough, BL DuPont, and RA
Maselli. Antibody effector mechanisms in myasthenia gravis. The complement hypothesis. Ann N Y Acad Sci. 1998 May 13; 841 :450-65
Kovacs, S.A., J. O’Neil, J. Watcharapijarn,
C. Kirvan , S. Vijay, and V. Silva.
Eubacterial components similar to small nuclear ribonucleoprotein particles:
Identification if immunoprecipitable proteins and capped RNAs in a cyanobacterium and a Gram-positive eubacterium. J. Bacteriology 1993 175 :1871-1878.
INVITED SPEAKER
Kirvan, CA. Update on the Pathogenesis of Streptococcus pneumoniae. California
Association of Medical Laboratory Technologist. State Meeting Sacramento CA
(10/2011), UC Davis Medical Center (2/2012)
Kirvan, CA. Update on Antibody-Mediated Mechanisms of Sydenham's Chorea and
Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS). Department of Microbiology and Immunology, University of
Oklahoma Health Sciences Center. 4/8/11
Kirvan, CA. Update on the Pathogenesis of Group A Streptococcus. California
Association of Medical Laboratory Technologist. Reno, NV (6/2010), Anaheim, CA
(10/2010), Visalia, CA (2/2011)
Kirvan, CA . Methicillin Update on Methicillin Resistant Staphylococcus aureus.
Sacramento Chapter for the American Association of Critical-Care Nurses.
2/4/2009
Kirvan, CA . Characterization of humoral responses in Sydenham's chorea and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS)”
UC Davis M.I.N.D. Institute 9/19/2008
Kirvan, CA. Characterization of h umoral responses in Sydenham’s chorea and Pediatric
Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections
(PANDAS). Lancefield International Symposium on Streptococci and Streptococcal
Disease. Porto Heli, Greece. 6/23/08.
Kirvan, CA, Antibody Mediated Neuronal Cell Signaling in Sydenham’s chorea and
Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus
(PANDAS). Lancefield International Symposium on Streptococci and Streptococcal
Disease. Cairns, Australia. 9/28/05.
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Kirvan, CA, Neuronal cell signaling in Pediatric Autoimmune Neuropyschiatric
Disorders Associated with Streptococcal infections. University of Utah, Salt Lake City,
UT. 8/22/05
Kirvan, CA , SE Swedo, JS Heuser, and MW Cunningham. Antibody-mediated neuronal cell signaling in Sydenham’s chorea. Lancefield International Symposium on
Streptococci and Streptococcal Disease. Goa, India. October 2002.
Kirvan, CA , SE Swedo, JS Heuser, and MW Cunningham. Antibody-mediated neuronal cell signaling in Sydenham’s chorea. Indo-US Vaccine Action Plan meeting.
Goa, India. October 2002.
ABSTRACTS
Kirvan, CA , SE Swedo, JS Heuser, and MW Cunningham. Anti-streptococcal/antiganglioside monoclonal antibodies in Sydenham’s induce neuronal cell signaling.
American Society for Microbiology. Salt Lake City, UT, USA. May 2002
Kirvan, CA , JS Heuser, and MW Cunningham. Anti-streptococcal monoclonal antibodies in Sydenham’s chorea target tubulin and ganglioside and induce neuronal cell signaling. Texas Regional Immunology Meeting. Oklahoma City, OK, USA. 11/01
Kirvan, CA , JS Heuser, and MW Cunningham. Anti-streptococcal monoclonal antibodies in Sydenham’s chorea target tubulin and ganglioside and induce neuronal cell signaling. Lancefield Society. San Francisco, CA, USA October 2001.
Kirvan, CA , JS Heuser, and MW Cunningham. Anti-streptococcal monoclonal antibodies in Sydenham’s chorea target tubulin and ganglioside and induce neuronal cell signaling. University of Oklahoma Immunology Retreat. Vinita, OK, USA.
October 2001.
Kirvan, CA , JS Heuser, and MW Cunningham. Tubulin and Gangliosides are Molecular
Targets of Anti-Streptococcal Monoclonal Antibodies from Syndenham’s Chorea.
American Society for Microbiology. Orlando, FL, USA. May 2001
Kirvan, CA , JS Heuser, and MW Cunningham. Characterization of anti-Brain
Monoclonal Antibodies from Streptococcus-induced Sydenham’s Chorea. Federation of
American Societies of Experimental Biology. Orlando, FL, USA. March 2001.
AWARDS AND ACADEMIC HONORS
Pedagogy Enhancement Award (2012)
C. M. Goethe Project Grant (2009)
C. M. Goethe Project Grant (2007)
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C. M. Goethe Project Grant (2004)
California State University Program for Education and Research in Biotechnology
Faculty Seed Grant (2004)
NIH/NIAID Immunology Training Grant for Postdoctoral Fellows (2001).
Henry R. Viets Fellowship (1996).
Henry R. Viets Fellowship (1992).
National Dean’s Honor List (1991).
California State University Program for Education and Research in Biotechnology
Travel Award (1990).
Outstanding Undergraduate Research Presentation-11th Annual Central California
Research Symposium (1990).
MEMBERSHIPS
American Society for Microbiology
Lancefield Society (Group A Streptococcus)
CLINICAL EXPERIENCE
Fresno Community Hospital, Fresno CA, microbiology laboratory assistant 1988-1991. duties included culture and isolation of bacteria from a variety of human sources including blood and body fluids, isolation of ova and parasite, culture and isolation of acid-fast bacilli including Mycobacterium tuberculosis, fungal culture, Gram staining, trichrome staining, Pneumocystis carnii staining, KOH, india ink, and LPCB fungal mounts, set-up of MIC, and routine quality control. Trained for proper handling of pathogens including sterile technique and biohazard precautions.
Valley Children’s Hospital, Fresno, CA, hematology laboratory assistant and phlebotomist 1988-1990. responsibilities included operation of coulter counter for CBC analysis, cytospin of cerebral spinal fluid, set-up of platelet counts, sedimentation rates, and Wright stains, routine quality control and phlebotomy. Trained in biohazard precautions of blood/body fluids and needles.
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TECHNICAL SKILLS
RNA isolation tissue culture/sterile technique
PCR (RT-PCR, 5’RACE) mammalian cell transfection site-directed mutagenesis gene expression
DNA sequencing protein purification plasmid manipulations/cloning ELISA western blotting radioisotope use antibody affinity studies complement activation assays immunohistochemistry in situ antigen detection column chromatography recombinant DNA/protein production immunoprecipitation immunohistochemisty gel-electrophoresis hybridoma production immunofluorescence bacterial culture techniques disease induction clinical evaluation of experimental animals signal transduction LDH cytotoxicity assays immunohistochemistry DNA array
REFERENCE CONTACTS
Available on request.
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