Hans Cheng |
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Research Interests
My lab is one of five groups in the Avian Disease and Oncology Laboratory, and we all share a common research goal. Thus, with our unique collection of inbred chickens lines and virus strains, we have a well-equipped multidisciplinary effort with expertise in molecular virology, pathology, immunology, and genetics to understand viral-induced cancers of the chicken.
My laboratory uses genomic and functional genomic approaches to identify and functionally characterize genes of agricultural importance in chicken, especially with regard to resistance to Marek’s disease (a herpesvirus-induced T cell cancer). Current projects include:
- Chicken genetic map - I lead the US effort, which forms the framework for the chicken genome assembly lead by Wes Warren (Genome Institute, Wash. U. in St. Louis)
- Molecular genetics and genomic selection for Marek’s disease resistance – Using an integrated genomics strategy (e.g., GWAS, RNA seq), we are identifying genes that confer genetic resistance to Marek’s disease. In addition, linked SNP markers, mainly based on allele-specific expression, are being used in genomic selection strategies in both experimental and commercial poultry flocks. Hi-C is also being employed to identify promoter-enhancer interactions with the hope of revealing causative polymorphisms that account for genetic resistance.
- Driver mutations for Marek’s disease – Hypothesizing that somatic mutations are required for transformation, various genomic strategies (e.g., DNA seq, RNA seq, cytogenetics) are being employed and integrated to identify driver genes.
- Vaccine synergy – Marek’s disease vaccines form the primary control method, however, very little information in known as to how they actually protect birds.
Education and Employment
1983 B.S., Michigan State University
1988 Ph.D., University of California at Berkeley
1988-90 Postdoctoal Fellow, University of California at Davis
1990-92 Molecular Geneticist, Petoseed, Woodland, CA
1992-date USDA, ARS
Key publications
Warren, W.C., Hillier, L.W. Tomlinson, C., Minx, P., Kremitzki, M., Graves, T., Markovic, C., Bouk, N., Pruitt, K.D., Thibaud-Nissen, F., Schneider, V., Mansour, T.A., Brown, C.T., Zimin, A., Hawken, R., Abrahamsen, M., Pyrkosz, A.B., Morisson, M., Fillon, V., Vignal, A., Chow, W., Howe, K., Fulton, J.E., Miller, M.M., Lovell, P., Mello, C.V., Wirthlin, M., Mason, A.S., Kuo, R., Burt, D.W., Dodgson, J.B., and Cheng, H.H. 2017. A new chicken genome assembly provides insight into avian genome structure. G3 7:109-117.
Cheng, H.H., Perumbakkam, S., Black Pyrkosz, A., Dunn, J.R., Legarra, A., and Muir, W.M. 2015. Fine mapping of QTL and genomic prediction using allele-specific expression SNPs demonstrates that the complex trait of genetic resistance to Marek’s disease is predominantly determined by transcriptional regulation. BMC Genomics 16:816.
Perumbakkam, S., Hunt, H.D., and Cheng, H.H. 2014. Marek’s disease virus influences the core gut microbiome of the chicken during the early and late phases of viral replication. FEMS Microbiol. Ecol. 90:300-312.
Hildebrandt, E., Dunn, J.R., Perumbakkam, S., Niikura, M, and Cheng, H.H. 2014. Characterizing the molecular basis of attenuation of Marek’s disease virus via in vitro serial passage identifies de novo mutations in the helicase-primase subunit gene UL5 and other candidates associated with reduced virulence. J. Virology 88:6232-6242.
Subramaniam, S., Johnston, J., Preeyanon, L., Brown, C.T., Kung, H.J., and Cheng, H.H. 2013. Integrated analyses of genome-wide DNA occupancy and expression profiling identify key genes and pathways involved in cellular transformation by Marek's disease oncoprotein, Meq. J. Virology 87:9016-9029.
Groenen, M.A.M., Megens, H.-J., Zare, Y., Warren, W.C., Hillier, L.W., Crooijmans, R.P.M.A., Vereijken, A., Okimoto, R., Muir, W.M., and Cheng, H.H. 2011. The development and characterization of a 60K SNP chip for chicken. BMC Genomics 12:274.
Robinson, C.M., Hunt, H.D., Cheng, H., and Delany, M. 2010. Mapping of Marek’s disease herpesvirus integrations into chicken chromosomes indicates positional preference for telomeres and clonal relationships among tumors. Herpesviridae 1:5.
Niikura, M., Kim, T., Silva, R.F., Dodgson, J., and Cheng, H.H. 2011. Virulent Marek’s disease virus generated from infectious bacterial artificial chromosome clones with complete DNA sequence and implication of viral genetic homogeneity in pathogenesis. J. Gen. Virol. 92:598-607.
Silva, R.F., Dunn, J.R., Cheng, H.H., and Niikura, M. 2010. A MEQ deleted Marek’s disease virus cloned as a bacterial artificial chromosome is a highly efficacious vaccine. Avian Diseases 54:862-869.
Tai, S.H.S., Niikura, M., Cheng, H.H., Kruger, J.M., Wise, A.G., and Maes, R.K. 2010. Complete genomic sequence and an infectious BAC clone of feline herpesvirus-1 (FHV-1). Virology 401:215-227.
Muir, W.M., Wong, G.K., Zhang, Y., Wang, J., Groenen, M.A. M, Crooijmans, R.P.M.A., Megens, H.-J., Zhang, H., Okimoto, R., Vereijken, A., Jungerius, A., Albers, G.A.A., Taylor Lawley, C., Delany, M.E., MacEachern, S., and Cheng, H.H. 2008. Genome-wide assessment of world-wide chicken SNP genetic diversity indicates significant absence of rare alleles in commercial breeds. PNAS 105:17312-17317.
Cheng, H.H., Zhang, Y., and Muir, W.M. 2007. Evidence for widespread epistatic interactions influencing Marek’s disease virus viremia levels in chicken. Cytogen. Genome Res. 117:313-318.
Niikura, M., Kim, T., Hunt, H.D., Burnside, J., Morgan, R.W., Dodgson, J.B., and Cheng, H.H. 2007. Marek's disease virus up-regulates major histocompatibility complex class II cell surface expression in infected cells. Virology 359:212-219.
Wong, G.K., Liu, B., Wang, J., Zhang, Y., Yang, X., Zhang, Z., Meng, Q., Zhou, J., Li, D., Zhang, J., Ni, P., Li, S., Ran, L., Li, H., Zhang, J., Li, R., Li, S., Zheng, H., Lin, W., Li, G., Wang, X., Zhao, W., Li, J., Ye, C., Dai, M., Ruan, J., Zhou, Y., Li, Y., He, X., Zhang, Y., Wang, J., Huang, X., Tong, W., Chen, J., Ye, J., Chen, C., Wei, N., Li, G., Dong, L., Lan, F., Sun, Y., Zhang, Z., Yang, Z., Yu, Y., Huang, Y., He, D., Xi, Y., Wei, D., Qi, Q., Li, W., Shi, J., Wang, M., Xie, F., Wang, J., Zhang, X., Wang, P., Zhao, Y., Li, N., Yang, N., Dong, W., Hu, S., Zeng, C., Zheng, W., Hao, B., Hillier, LW., Yang, SP., Warren, W.C., Wilson, R.K., Brandstrom, M., Ellegren, H., Crooijmans, R.P., van der Poel, J.J., Bovenhuis, H., Groenen, M.A., Ovcharenko, I., Gordon, L., Stubbs, L., Lucas, S., Glavina, T., Aerts, A., Kaiser, P., Rothwell, L., Young, J.R., Rogers, S., Walker, B.A., van Hateren, A., Kaufman, J., Bumstead, N., Lamont, S.J., Zhou, H., Hocking, P.M., Morrice, D., de Koning, D.J., Law, A., Bartley, N., Burt, D.W., Hunt, H., Cheng, H.H., Gunnarsson, U., Wahlberg, P., Andersson, L., Kindlund, E., Tammi, M.T., Andersson, B., Webber, C., Ponting, C.P., Overton, I.M., Boardman, P.E., Tang, H., Hubbard, S.J., Wilson, S.A., Yu, J., Wang, J., Yang, H; International Chicken Polymorphism Map Consortium. 2004. A genetic variation map for chicken with 2.8 million single-nucleotide polymorphisms. Nature 432:717-722.
Wallis, J.W., Aerts, J., Groenen, M.A., Crooijmans, R.P., Layman, D., Graves, T.A., Scheer, D.E., Kremitzki, C., Fedele, M.J., Mudd, N.K., Cardenas, M., Higginbotham, J., Carter, J., McGrane, R., Gaige, T., Mead, K., Walker, J., Albracht, D., Davito, J., Yang, S.P., Leong, S., Chinwalla, A., Sekhon, M., Wylie, K., Dodgson, J., Romanov, M.N., Cheng, H., de Jong, P.J., Osoegawa, K., Nefedov, M., Zhang, H., McPherson, J.D., Krzywinski, M., Schein, J., Hillier, L., Mardis, E.R., Wilson, R.K., and Warren, W.C. 2004. A physical map of the chicken genome. Nature 432:761-764.
Niikura, M., Liu, H.-C., Dodgson, J.B., and Cheng, H.H. 2004. A comprehensive screen for chicken proteins that interact with proteins unique to virulent strains of Marek’s disease virus. Poultry Science 83:1117-1123.
Liu, H.-C., Cheng, H.H., Softer, L. and Burnside, J. 2001. A strategy to identify positional candidate genes conferring Marek’s disease resistant by integrating DNA microarrays and genetic mapping. Anim. Genet. 32:351-359.
Liu, H.-C., Kung, H.-J., Fulton, J.E., Morgan, R.W. and Cheng, H.H. 2001. Growth hormone interacts with the Marek’s disease virus SORF2 protein and is associated with disease resistance in chicken. PNAS 98:9203-9208.
Bacon, L.D., Hunt, H.D. and Cheng, H.H. 2000. A review of the development of chicken lines to resolve genes determining resistance to diseases. Poultry Sci. 79:1082-1093.
Groenen, M.A.M., Crooijmans, R.P.M.A., Veenendall, A., Cheng, H.H., Siwek, M. and van der Poel, J.J. 1998. A comprehensive microsatellite linkage map of the chicken genome. Genomics 49:265-274.
Liu, W.-T., Marsh. T.L., Cheng, H. and Forney, L.J. 1997. Characterization of microbial diversity by determining terminal restriction fragment length polymorphisms of 16S ribosomal DNA. Appl. Environ. Microbiol. 63:4516-4522.
Cheng, H.H. and Crittenden, L.B. 1994. Microsatellite markers for genetic mapping in the chicken. Poultry Sci. 73:539-546.
Cheng, H.H., Muhlrad, P.J., Hoyt, M.A., Crowl, R. and Echols, H. 1988. Cleavage of the cII protein of phage l by purified HflA protease: control of the switch between lysis or lysogeny. PNAS 85:7882-7886.
Current Personnel
Postdoctoral Associates
- Alexis Black Pyrkosz
Graduate Students
- Cari Hearn – CMIB
- Alec Steep – Genetics Program
- Sudawapee Umthong – Microbiology
Undergraduate Student
- Kalee Rumfelt
Technician
- Laurie Molitor
Additional External Funding Beyond ARS Support
- USDA AFRI, Enhancing genetic resistance to Marek’s disease in chicken via allele-specific expression screens and genome-wide selection; PI
- USDA AFRI, Genome biology of Marek’s disease: Viral integration and genome alterations in genetically resistant and susceptible stocks: PI
- USDA AFRI, The role of host genetic resistance and vaccination on transmission of Marek’s disease virus in poultry; co-PI.
- USDA National Needs Graduate Fellowship Grants; co-PI