Dr. Zhu's research goals are to discover and characterize the activities of large collections of proteins to build signaling networks for better understanding the mechanisms of biological processes, and to identify biomarkers for important human diseases. More specifically, Dr. Zhu and his team are interested in analyzing protein posttranslational modifications, identifying important components involved in various signaling networks and studying host-pathogen interactions on the proteomics level.
Dr. Zhu's lab has developed two key technologies: high-throughput protein purification (>4,000 proteins/day) and high-density protein microarrays/chip (>15,000 protein/slide). So far, they have fabricated proteome chips in the budding yeast, herpesviruses and E. coli (K12). They are also currently working on building a focused protein chip in humans. Previously, they and other researchers demonstrated that protein chips could be used to characterize various protein-binding properties, including protein-protein, protein-DNA, protein-lipid and protein-drug interactions, and to identify downstream targets of protein kinases.
More recently, Dr. Zhu's team and their colleagues have made significant progress in expanding the application of protein chips in the following directions: 1) novel protein binding assays, such as RNA-protein, live cell-protein and lectin-protein interactions; 2) novel enzymatic reactions, including protein ubiquitination and acetylation, 3) human serum profiling and 4) a novel approach in protein chip fabrication. The above new assays or approaches have been applied to investigate host-pathogen interactions, protein glycosylation, cell surface glycan profiles, a ubiquitin E3 enzyme in yeast and biomarker identification in human inflammatory bowel diseases. Their recent progress has been highlighted in five publications. They strongly believe that the protein chip technologies are capable of accumulating massive amount of data to allow comprehensive and systematic analyses of complex eukaryotic proteomes.
Lab Website: Zhu Lab
Hu S, Wan J, Su Y, Song Q, Zeng Y, Nguyen HN, Shin J, Cox E, Rho HS, Woodard C, Xia S, Liu S, Lyu H, Ming GL, Wade H, Song H, Qian J, Zhu H. "DNA methylation presents distinct binding sites for human transcription factors." Elife. 2013 Sep 3;2:e00726. doi: 10.7554/eLife.00726.
Newman RH, Hu J, Rho HS, Xie Z, Woodard C, Neiswinger J, Cooper C, Shirley M, Clark HM, Hu S, Hwang W, Jeong JS, Wu G, Lin J, Gao X, Ni Q, Goel R, Xia S, Ji H, Dalby KN, Birnbaum MJ, Cole PA, Knapp S, Ryazanov AG, Zack DJ, Blackshaw S, Pawson T, Gingras AC, Desiderio S, Pandey A, Turk BE, Zhang J, Zhu H, Qian J. "Construction of human activity-based phosphorylation networks." Mol Syst Biol. 2013;9:655. doi: 10.1038/msb.2013.12.
Jeong JS, Jiang L, Albino E, Marrero J, Rho HS, Hu J, Hu S, Vera C, Bayron-Poueymiroy D, Rivera-Pacheco ZA, Ramos L, Torres-Castro C, Qian J, Bonaventura J, Boeke JD, Yap WY, Pino I, Eichinger DJ, Zhu H, Blackshaw S. "Rapid identification of monospecific monoclonal antibodies using a human proteome microarray." Mol Cell Proteomics. 2012 Jun;11(6):O111.016253. doi: 10.1074/mcp.O111.016253. Epub 2012 Feb 3.
Lu JY, Lin YY, Sheu JC, Wu JT, Lee FJ, Chen Y, Lin MI, Chiang FT, Tai TY, Berger SL, Zhao Y, Tsai KS, Zhu H, Chuang LM, Boeke JD. "Acetylation of yeast AMPK controls intrinsic aging independently of caloric restriction." Cell. 2011 Sep 16;146(6):969-79. doi: 10.1016/j.cell.2011.07.044. Epub 2011 Sep 9.
Hu S, Xie Z, Onishi A, Yu X, Jiang L, Lin J, Rho HS, Woodard C, Wang H, Jeong JS, Long S, He X, Wade H, Blackshaw S, Qian J, Zhu H. "Profiling the human protein-DNA interactome reveals ERK2 as a transcriptional repressor of interferon signaling." Cell. 2009 Oct 30;139(3):610-22. doi: 10.1016/j.cell.2009.08.037.