OVERALL RESEARCH SUMMARY

We are interested in the identification and characterization of novel viruses. In our work, we integrate a variety of experimental methodologies that cross many disciplines including molecular biology, classic virology, genomics, epidemiology, clinical investigation and bioinformatics.

Genomic approaches to viral discovery: We utilize cutting edge genomic methods to systematically search for viruses in an unbiased fashion. This includes massively parallel screening using a pan-viral DNA microarray (ViroChip) and high throughput shotgun sequencing. Both of these methods have been extensively validated in our laboratory. The ViroChip currently contains ~22,000 viral 70mers designed from all human, animal, plant and insect viruses in Genbank. By strategic targeting a mixture of highly conserved and unique sequences for representation on the microarray, the ViroChip is capable of detecting thousands of known viruses as well as novel viruses with homology to known viral families. During the 2003 SARS oubreak, the ViroChip played a key role in the identification of SARS as a novel coronavirus. A complementary approach, high throughput sequencing, entails making random clone libraries from clinical specimens, sequencing large numbers of clones, and computationally identifying any clones with homology to known viruses. We have recently described a novel polyomavirus, WU virus, detected in patients with acute respiratory tract infections using this methodology.

Diseases of unknown etiology: We are currently investigating a number of diseases of unknown etiology using these methodologies. A significant effort in the laboratory is focused on diseases of the respiratory tract, the central nervous system, and the gastrointestinal tract. Although many known viruses have been implicated in these diseases, epidemiological investigations typically fail to identify an infectious agent in ~ 30% of respiratory infections, ~75% of encephalitis cases, and ~30% of cases of acute diarrhea, suggesting that novel pathogens are likely to exist. In addition we are applying these viral discovery methods to a number of other diseases, including human cancers, where viruses have been postulated to play a role in disease etiology.

Viral diversity and surveillance: The past two decades have witnessed the emergence of many significant viral pathogens including HIV, Sin nombre hantavirus, nipah virus, avian influenza and SARS. Subsequent investigations revealed that in each of these cases, the viruses emerged from an animal reservoir. In fact, it has been estimated the 75% of all emerging diseases are zoonotic in nature. These studies highlight the importance of understanding viral diversity in animal and insect reservoirs and vectors. Thus we are interested in proactively elucidating the spectrum of viruses present in rodents, bats, mosquitoes, ticks.

Characterization of WU polyomavirus: We have identified a novel virus referred to as WU virus in the family Polyomaviridae by screening of human respiratory secretions. Two human polyomaviruses, BK and JC, were identified in 1971 and infect the majority of humans around the world. These two viruses are closely related to each other and are both are pathogenic in immunocompromised individuals. Earlier this year, a third polyomavirus, KI, was described in human clinical specimens, although its pathogenicity and prevalence in humans has not yet been established. The discovery of WU virus brings the number of polyomaviruses detected in humans to four. WU differs from BK and JC significantly in its genome sequence and in its relative tissue tropism, suggesting that it is likely to have unique biological properties. This discovery raises many questions for further investigation such as: Is WU virus a human pathogen? If so, what kind of disease does it cause? Where in the body does WU virus reside? At what age does infection typically occur? Perhaps most importantly, there are likely to be many more as of yet unidentified viruses infecting the human body.

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Present position
2004-	Assistant Professor of Molecular Microbiology and Pathology&Immunology Washington University School of Medicine
Education/Training
1988-1992	B.S. Chemistry, Stanford University
1992-1998	Ph.D. Biological Chemistry, Massachusetts Institute of Technology
1998-2004	Postdoctoral Fellow, University of California, San Francisco

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Selected Publications

Finkbeiner, Stacy R.; Allred, Adam F.; Tarr, Phillip I.; Klein, Eileen J.; Kirkwood, Carl D.; Wang, David; “Metagenomic Analysis of Human Diarrhea: Viral Detection and Discovery” PLoS Pathogens (2008) e1000011.

Mihindukulasuriya, K.A.; Wu, G.; St. Leger, J.; Nordhausen, R.W.; Wang, D.; “Identification of a novel coronavirus from a beluga whale using a pan-viral microarray” Journal of Virology 82 (2008) 5084.

Le, Binh-Minh; Demertzis, Lee M.; Wu, Guang; Tibbets, Robert J.; Buller, Richard; Arens, Max Q.; Gaynor, Anne, M.; Storch, Gregory A.; Wang, David; “Clinical and Epidemiologic Characterization of WU Polyomavirus Infection in St. Louis, USA” Emerging Infectious Diseases (2007)

Kistler, Amy, Avila, Pedro C.; Rouskin, Silvi; Wang, David; Ward, Theresa; Yagi, Shigeo; Schnurr, David, Ganem, Don; DeRisi, Joseph L.;Boushey, Homer A.; “Pan-viral screening of respiratory tract infections in asthmatic and non-asthmatic adults reveals unexpected coronavirus and human rhinovirus diversity” Journal of Infectious Diseases 196 (2007) 817-25.

Gaynor Anne M.; Nissen, Michael D.; Whiley, David M.; Mackay, Ian M.; Wu, Guang; Brennan, Daniel C.; Storch, Gregory A.; Sloots, Theo P. Wang, David. “Identification of a novel polyomavirus from patients with acute respiratory tract infections” PLoS Pathogens 3 (2007) e64. doi:10.1371/journal.ppat.0030064.

Sang, R.; Onyango, C.; Gachoya, J.; Mabinda, E.; Konongoi, S.; Ofula, V.; Dunster, L.; Okoth, F.; Coldren, R.; Tesh, R.; Travassos da Rosa, A.; Finkbeiner, S.; Wang, D.; Crabtree, M.; Miller, B.; “ Tickborne arbovirus surveillance in market livestock, Nairobi, Kenya ”Emerging Infectious Diseases 12 (2006) 1074.

Urisman, Anatoly; Fischer, Kael F; Chiu, Charles Y; Kistler, Amy L; Beck Shoshannah; Wang, David; DeRisi, Joseph L;“E-predict: a computational strategy for species identification based on observed DNA microarray hybridization patterns” Genome Biology 6 (2005) R78.

Wang, David; Urisman, Anatoly; Liu, Yu-tsueng; Springer, Michael; Ksiazek, Thomas G.; Erdman, Dean D.; Mardis, Elaine R.; Hickenbotham, Matthew; Magrini, Vincent; Eldred, James; Latreille, J. Phillipe; Wilson, Richard K.; Ganem, Don; DeRisi, Joseph L. “Viral discovery and sequence recovery using DNA microarrays”PLoS Biology 1 (2003) 257.

Rota, Paul A.; Oberste, M. Steven; Monroe, Stephan S.; Nix, W. Allan; Campagnoli, Ray; Icenogle, Joseph; Peneranda, Silvia, Bankamp, Bettina; Maher, Kaija; Chen, Min-hsin; Tong, Suxiong; Tamin, Azaibi; Lowe, Luis; Frace, Michael; DeRisi, Joseph L.; Chine, Qi; Wang, David; Erdman, Dean; Peret, Teresa; Burns, Cara; Ksiazek, Thomas G.; Rollin, Pierre E.; Sanchez, Anthony; Liffick, Stephanie; Holloway, Brian; Limor, Josef; McCaustland, Karen; Olson-Rassmussen, Melissa; Fouchier, Ron; Gunther, Stephan; Osterhaus, Albert; Drosten, Christian; Pallansch, Mark; Anderson, Larry J.; Bellini, William J. “Characterization of a novel coronavirus causing severe acute respiratory syndrome” Science, 300 (2003) 1394.

Wang, David; Coscoy, Laurent; Zylberberg, Maxine; Avila, Pedro C.; Boushey, Homer A.; Ganem, Don; DeRisi, Joseph L. “Microarray-based detection and genotyping of viral pathogens” Proceedings of the National Academy of Sciences (USA), 99 (2002) 15687.

Polson, Andrew; Wang, David; DeRisi, Joseph; Ganem, Don “Modulation of host cell gene expression by the constitutively active G-protein coupled receptor of Kaposi’s sarcoma herpes virus (KSHV)” Cancer Research, 62 (2002) 4525.

Wang, David; Pearlberg, Joseph; Liu, Yu-tsueng; Ganem, Don. “Deleterious effects of hepatitis delta virus replication on host cell proliferation” Journal of Virology, 75 (2001) 3600.  

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