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Dong Yu
Assistant
Professor 9220D McDonnell Pediatric Research Building Department of Molecular
Microbiology Campus Box 8230 Affiliated
Graduate Programs: DBBS
Homepage: http://dbbs.wustl.edu/ Microbial
Pathogenesis Program: http://dbbs.wustl.edu/programs/micro Molecular
Cell Biology Program: http://dbbs.wustl.edu/programs/cellbio Molecular
Genetics and Genomics Program: http://dbbs.wustl.edu/dbbs/website.nsf/WV/9A02B0DEF211B91386256D4F00694D4D?OpenDocument |
My laboratory studies the molecular mechanisms of human cytomegalovirus (HCMV) replication and pathogenesis. HCMV is a beta-herpesvirus, contains a 250-kb double-stranded DNA genome and encodes more than 150 viral genes. HCMV is a ubiquitous pathogen that establishes a life-long latent infection and recurrent reactivation in the human host. HCMV is the leading viral cause of birth defects in the United States and a major cause of disease in immuno-compromised hosts, including cancer patients, patients with HIV infection, and recipients of bone marrow and solid organ transplants. In addition, HCMV has also been associated with various vascular diseases such as atherosclerosis and restenosis.
We have developed the infectious bacterial artificial chromosome (BAC)-based reverse genetic system for HCMV, and we have defined the entire set of 156 HCMV genes into 3 functional categories (88 non-essential genes, 41 essential genes, and 27 important genes). Our current research focuses on the interface of virus-host interactions. In particular, we are interested in understanding how the host controls HCMV replication (e.g., apoptosis, interferon), how HCMV evades anti-viral responses, and how the virus modulates host processes (e.g., cellular gene expression, cell cycle control) to create a favorable environment needed for its replication. We use cellular and virological approaches to study HCMV biology in multiple cell culture systems and we also use mouse cytomegalovirus (MCMV) as the surrogate model for studying roles of the conserved CMV genes in viral pathogenesis in vivo.
We have recently identified the functions of several viral proteins that are important in HCMV infection. For instance, we found that the HCMV protein pUL38 functions as an inhibitor to block endoplasmic reticulum-induced cell death and that the viral protein pUL117 modulates the architecture of replicating viral DNA to promote HCMV replication. Our other research efforts focus on viral proteins regulating host cell cycle control, modulating DNA damage responses, suppressing interferon signaling pathways, and promoting virus replication in various cultured human cells that are natural targets of HCMV in vivo.
Keywords: Cytomegalovirus, DNA virus, virology, viral evasion, molecular biology, genetics, microbial pathogenesis
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Present
Position |
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09/2004- |
Assistant
Professor |
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01/2006- |
Research Associate Member Siteman NCI Comprehensive Cancer Center, Washington University School of Medicine, St. Louis, MO |
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08/1998 |
Ph.D.
Biochemistry and Molecular Biology, University of Connecticut Health Center,
Farmington, CT |
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07/1991 |
B.S.
Biochemistry, Fudan University, Shanghai, China |
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01/2006- |
Research Associate Member, Siteman NCI Comprehensive Cancer Center |
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09/2004- |
Assistant
Professor |
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08/1999-09/2004 |
Postdoctoral
Fellow |
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08/1998-08/1999
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Postdoctoral
Fellow |
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2008-2013 |
Investigator
in the Pathogenesis of Infectious Disease, Burroughs Wellcome Fund |
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2005-2007 |
Wyeth
Young Investigator Award in Vaccine Development, the Infectious Diseases
Society of America
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2003-2008 |
Howard
Temin Career Development Award, National Institute of Health |
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2000-2003 |
Fellow,
the Leukemia & Lymphoma Society of America |
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1999 |
Edward
G. Henderson Prize for Outstanding Ph.D. Thesis Research, University of
Connecticut |
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University and Hospital Appointments and
Committees |
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09/2006- |
PhD Admissions Committee, The Division of Biology and
Biomedical Sciences, Washington University, St. Louis, MO |
1. Yu, D., G.A. Smith, L.W. Enquist and T. Shenk (2002) Construction of a self-excisable bacterial artificial chromosome containing the human cytomegalovirus genome and mutagenesis of the diploid TRL/IRL13 gene. J. Virol. 76 (5): 2316-2328.
2. Yu, D., M.C. Silva and T. Shenk (2003) Functional map of human cytomegalovirus AD169 defined by global mutational analysis. Proc Natl Acad Sci USA 100 (21): 12396-12401.
3. Murphy, E., D. Yu, J. Grimwood, J. Schmutz, M. Dickson, M. Jarvis, G. Hahn, J.A. Nelson, R.M. Myers and T. Shenk (2003) Coding potential of laboratory and clinical strains of human cytomegalovirus. Proc Natl Acad Sci USA 100 (25): 14976-14981.
4. Terhune, S., E. Torigoi, N. Moorman, M. Silva, Z. Qian, T. Shenk, and D. Yu (2007) Human cytomegalovirus UL38 protein blocks apoptosis. J. Virol. 81 (7): 3109-3123.
5. Qian, Z., B. Xuan, T. T. Hong, and D.
Yu (2008) The full-length protein encoded by human cytomegalovirus gene UL117
is required for the proper maturation of viral replication compartments. J.
Virol. 82 (7): 3452-3465.