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Pathology and Microbiology

Steven Tracy, Ph.D., Professor

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ACADEMIC DEGREES:

Department of Biology, UCSD, BA, 1972
Graduate School Department of Biology, UCSD, PhD, 1979
Post-doctoral Training UCSD Department of Medicine

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Contact Name: Steven Tracy Ph.D.
Phone Numbers: 559-7747, 559-7697
e-mail address:  stracy@unmc.edu

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CURRENT
American Diabetes Association, "Coxsackievirus induction of insulitis in young NOD mice". PI, $97,654 total direct costs, 02/05-01/07

Juvenile Diabetes Research Foundation (JDRF) International, Research Grant, "Coxsackievirus modulation of T1D outcome in NOD mice." PI, $480,000 total direct costs, 02/05-01/08

NIH, 1P20 RR018788-01, "The Molecular Biology of Neurosensory Systems" (S. Smith, P.I.), total direct costs, $10.7 million.  Project 2: Role of neuregulins in myelin repair in the CNS and PNS (K. Drescher, P.I.), total direct costs, $1.6 million, 09/03-06/08. Consultant, 5% FTE

PAST
1993-1997 National Institutes of Health, 2-RO1-HL40303
1997-1999 American Heart Association, Nebraska Affiliate
1998-2000 NIH, 1-R21-A142153
2002-2004 NATO Collaborative Linkage Grant
2002-2004 American Heart Association-NE Affiliate
2002-2005 Juvenile Diabetes Research Foundation (JDRF) International

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Tracy S, Drescher KM, Chapman NM, Kim K-S, Carson SD, Pirruccello S, Lane PH, Romero JR, and Leser JS (2002) Toward testing the hypothesis that group B coxsackieviruses (CVB) trigger insulin-dependent diabetes: Inoculating NOD mice with CVB markedly lowers diabetes incidence. J Virol 76:12097-12111.

Dunn J, Bradrick S, Chapman N, Tracy S, Romero J (2003) The stem loop II within the 5' nontranslated region of clinical coxsackievirus B3 genomes determines cardiovirulence phenotype in a murine model.  J Infect Dis.187:1552-61.

Drescher KM, Kono K, Bopegamage S, Carson SD, Tracy S (2004)  Coxsackievirus B3 infection and type 1 diabetes development in NOD mice: Insulitis determines susceptibility of pancreatic islets to virus infection. Virology 329:381-394.

Lee CK, Kono K, Haas E, Kim KS, Drescher KM, Chapman NM, Tracy S. (2005)     Characterization of an infectious cDNA copy of the genome of a naturally-occurring,    avirulent coxsackievirus B3 clinical isolate. J General Virology 86:197-210

Kim K-S, Tracy S, Tapprich W, Bailey J, Lee C-K, Kim K, Barry W, Chapman N. (2005) 5' Terminal deletions occur in coxsackievirus B3 during replication in murine hearts and cardiac myocyte cultures and correlate with encapsidation of negative-strand viral RNA.  J Virol 79:7024-7041. 

Tracy S, Drescher KM, Chapman N, Kono K, Tapprich W (2006) Evolution of virulence in picornaviruses. Curr Topics Microbiol Immunol "Quasispecies: Concept and implications for virology" (editor: E. Domingo) 299:193-210. 

Kanno T, Kim K, Kono K, Chapman NM, Tracy S (2005,  in review) Group B coxsackievirus diabetogenic phenotype correlates with replication efficiency. J Virol 

Drescher KM and Tracy S (2006, in preparation) Group B coxsackievirus replication in NOD mouse islets:           virus associates with all major islet cell populations. 

Matsumori A, Shimada T, Chapman NM, Tracy S, Mason JW (2006, in press) Myocarditis and heart failure associated with hepatitis C virus infection. J Cardiac Failure.

REVIEWS
Kim K, Kanno T, Tracy S (2006, submitted) Virulence phenotypes in the group B coxsackieviruses. Future Virology 

Drescher KM and Tracy S (2006, in preparation) Human enteroviruses and the etiology of type 1 diabetes.  Future Virology

CHAPTERS
Chapman N, Gauntt C, Tracy S (2002) Immune responses to coxsackievirus infections. pp. 391-404.  In: The Picornaviruses.  B Semler, E Wimmer, eds.; Plenum Press, New York.

Kim K-S, Hofling K, Chapman NM, Tracy S (2002) The primary viruses of myocarditis. pp. 23-54  In:  Myocarditis: From Bench to Bedside. Cooper LS, Knowlton K, eds.; Mayo Academic Press, Rochester MN.

Kim K-S, Hofling K, Chapman NM, Tracy S (2002) Cardiotropic viruses. In: Myocarditis.  Cooper LS, Knowlton K, eds.; Mayo Academic Press, Rochester MN.

Chapman N, Kim K-S, Tracy S (2003) The group B coxsackieviruses as vaccines and vectors.  In: Cardiomyopathy and Heart Failure. Matsumori A, ed. Kluwer Academic Publishers, Norwell MA.

WWW PUBLICATIONS
Kim K-S, Chapman N, Tracy S (2005) Enteroviruses.  In: The Embryonic Encyclopedia of Life Sciences.  Nature Publishing Group; London.  http://www.els.net

  • PREVIOUS GRADUATE STUDENTS/POST-DOCTORAL FELLOWS (present location):

POST-DOCS
Melinda Beck, Ph.D., Post-Doctoral Scientist, 1988-1990. UNC/Chapel Hill
Katja Höfling, M.D., Post-Doctoral Scientist 1999 - 2000. Germany
Kyung-Soo Kim, Post-Doctoral Scientist 1999 - 2003 (UNMC)
Ken Kohno, M.D., Post-Doctoral Scientist 2002 - 2004. (Kitasato University)
Chang Kyu Lee, M.D., Visiting Assistant Professor, 2002-2003 [Korea University, Korea]
Akira Ukimura, M.D., Ph.D., Visiting Assistant Professor, 2002 [Osaka Medical College]
Yoon Seok Chung, Ph.D., Visiting Scientist, 2004 [National Institutes of Health, Korea]
Kisoon Kim, Ph.D., Post-Doctoral Scientist 2004- [UNMC]
Toru Kanno, DVM, PhD, Post-Doctoral Scientist 2005-

PHD AND MS GRADUATE STUDENTS
1987     MS Ulrike Fortmüller-Sippel. Georg-August-Universität, Göttingen Germany.
1987     MS Angelika Friedrich. Georg-August-Universität, Göttingen Germany.
1992     MS Julie Carstens. University of Nebraska Medical Center, Omaha NE.
1993     PHD Beth-Ann Griswold-Coller. Smith-Klein-Beecham, Brussels, Belgium.
1994     PHD Zhongheng Tu.  Unknown.
1995     PHD John Mullican.  Washburn University, KS.
1997     MS Anna Ragland. University of Arizona, Tucson AZ.
1999     PHD Sandra Willian.  EPA, Cincinnatti OH.

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This laboratory focuses on the molecular biology of an important group of human viruses called the group B coxsackieviruses (CVB).  These are enteroviruses (Picornavirus family), similar to but distinct from the other well-known enterovirus group, the polioviruses.  The CVB comprise six serotypes (CVB1-6); we focus on using the CVB3 as our model for the majority of our work.  As the worldwide effort to eradicate poliovirus continues toward completion, the CVB are increasingly highlighted as the enterovirus of choice for enteroviral research. The CVB are known to cause myocarditis (inflammation of the heart), a disease that can be rapidly fatal in babies; dilated cardiomyopathy, a leading cause for heart transplantation; aseptic meningitis; pancreatitis; and other conditions. Although infectious diseases kill more people worldwide than any other causes and represent a serious problem in the US as well, research on infectious diseases at medical schools have, oddly enough, often been ignored in favor of more high profile areas.  Now that the US perceives itself threatened by potential bioterrorism actions, the study of infectious disease organisms and viruses are rightfully acquiring greater respect. 

This laboratory studies how CVB are involved in two significant human diseases, insulin dependent (type 1) diabetes mellitus and myocarditis. Additionally, we continue our interest in developing the CVB as a vaccine as well as gene expression vector for potential human clinical use.

Studies on T1D in the NOD mouse have demonstrated a rational relationship between virus infection and either protection from, or sudden onset of, T1D.  Interest now focuses on the nature of the T cell response invoked by CVB infection which results in protection from the autoimmune disease, as well as the genetics of CVB virulence phenotypes, which play a significant role in this relationship.  Studies on CVB involvement in myocarditis focus on defining how CVB persist and replicate in heart through a recently discovered, novel mutation that naturally occurs in these viruses, as well as understanding viral genetics of virulence.

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Molecular biology of picornaviruses, cell and virus culture, development of enterovirus vectors, mouse models for myocarditis and for type 1 diabetes.

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