Dr. Heng Zhu
Associate Professor of Pharmacology & Molecular Sciences
Associate Professor of Oncology
Co-Director of the High-Throughout Biology Center
B.S., Peking University Ph.D., Clemson University
Postdoctoral Fellow in proteomics, Yale University, New Haven, CT
Proteomics and systems biology
Fueled by the ever-growing DNA sequence information, the field of proteomics has become one of the most important disciplines to characterize protein function and activity and provide insight into functional networks on a global scale. Emerging evidences suggest that proteins rarely act as single, isolated species when performing their function in vivo; they normally associate with other proteins and/or molecules as complexes and function in a network mode. The goals of my laboratory 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, our group is interested in analyzing protein posttranslational modifications, identifying important components involved in various signaling networks, and host-pathogen interactions on the proteomics level.
To achieve the above goals we developed two key technologies: high-throughput protein purification (>4,000 proteins/day) and high-density protein microarrays/chip (>15,000 protein/slide). So far, we have fabricated proteome chips in the budding yeast, herpesviruses, and E. coli (K12). We are also currently working on building a focused protein chip in humans. Previously, we and others 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, we and 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. Our recent progress has been highlighted in five publications. We 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.
Chen, C.S.; Zhu, H. Protein microarrays. Biotechniques. 2006 Apr;40(4):423, 425, 427 passim.
Tao, S.C.; Zhu, H. Protein chip fabrication by capture of nascent polypeptides. Nat Biotechnol. 2006 Oct;24(10):1253-1254.
Zhu, H.; Zhang, L.; Itoh, K.; Yamamoto, M.; Ross, D.; Trush, M.A.; Zweier, J.L.; Li, Y. Nrf2 controls bone marrow stromal cell susceptibility to oxidative and electrophilic stress. Free Radic Biol Med. 2006 Jul 1;41(1):132-143.
Hu, S.; Li, Y.; Liu, G.; Song, Q.; Wang, L.; Han, Y.; Zhang, Y.; Song, Y.; Yao, X.; Tao, Y.; Zeng, H.; Yang, H.; Wang, J.; Zhu, H.; Chen, Z.N.; Wu, L. A protein chip approach for high-throughput antigen identification and characterization. Proteomics. 2007 Jun;7(13):2151-2161.
Tao, S.C.; Chen, C.S.; Zhu, H. Applications of protein microarray technology. Combinatorial chemistry & high throughput screening. 2007 Sep;10(8):706-718.
Zhu, H.; Cao, Z.; Zhang, L.; Trush, M.A.; Li, Y. Glutathione and glutathione-linked enzymes in normal human aortic smooth muscle cells: chemical inducibility and protection against reactive oxygen and nitrogen species-induced injury. Mol Cell Biochem. 2007 Jul;301(1-2):47-59.
Zhu, H.; Jia, Z.; Mahaney, J.E.; Ross, D.; Misra, H.P.; Trush, M.A.; Li, Y. The highly expressed and inducible endogenous NAD(P)H:quinone oxidoreductase 1 in cardiovascular cells acts as a potential superoxide scavenger. Cardiovascular toxicology. 2007;7(3):202-211.
Zhu, H.; Zhang, L.; Trush, M.A.; Li, Y. Upregulation of endogenous glutathione system by 3H-1,2-dithiole-3-thione in pancreatic RINm5F beta-cells as a novel strategy for protecting against oxidative beta-cell injury. Free radical research. 2007 Feb;41(2):242-250.
Zhu, J.; Gopinath, K.; Murali, A.; Yi, G.; Hayward, S.D.; Zhu, H.; Kao, C. RNA-binding proteins that inhibit RNA virus infection. Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3129-3134.
Chen, C.S.; Korobkova, E.; Chen, H.; Zhu, J.; Jian, X.; Tao, S.C.; He, C.; Zhu, H. A proteome chip approach reveals new DNA damage recognition activities in Escherichia coli. Nat Methods. 2008 Jan;5(1):69-74.
Evans-Nguyen, K.M.; Tao, S.C.; Zhu, H.; Cotter, R.J. Protein arrays on patterned porous gold substrates interrogated with mass spectrometry: Detection of peptides in plasma. Anal Chem. 2008 Mar 1;80(5):1448-1458.
Huh, Y.H.; Kim, Y.E.; Kim, E.T.; Park, J.J.; Song, M.J.; Zhu, H.; Hayward, G.S.; Ahn, J.H. Binding STAT2 by the acidic domain of human cytomegalovirus IE1 promotes viral growth and is negatively regulated by SUMO. J Virol. 2008 Nov;82(21):10444-10454.
Jia, Z.; Zhu, H.; Trush, M.A.; Misra, H.P.; Li, Y. Generation of superoxide from reaction of 3H-1,2-dithiole-3-thione with thiols: implications for dithiolethione chemoprotection. Mol Cell Biochem. 2008 Jan;307(1-2):185-191.
Liu, X.; Yu, X.; Zack, D.J.; Zhu, H.; Qian, J. TiGER: A database for tissue-specific gene expression and regulation. BMC Bioinformatics. 2008;9:271.
Tao, S.C.; Li, Y.; Zhou, J.; Qian, J.; Schnaar, R.L.; Zhang, Y.; Goldstein, I.J.; Zhu, H.; Schneck, J.P. Lectin microarrays identify cell-specific and functionally significant cell surface glycan markers. Glycobiology. 2008 Oct;18(10):761-769.
Zhu, H.; Jia, Z.; Zhang, L.; Yamamoto, M.; Misra, H.P.; Trush, M.A.; Li, Y. Antioxidants and phase 2 enzymes in macrophages: regulation by Nrf2 signaling and protection against oxidative and electrophilic stress. Experimental biology and medicine (Maywood, NJ. 2008 Apr;233(4):463-474.
Hu, S.; Xie, Z.; Onishi, A.; Yu, X.; Jiang, L.; Lin, J.; Rho, H.S.; Woodard, C.; Wang, H.; Jeong, J.S.; 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):610-622.
Krishna, R.; Gumbiner, B.; Stevens, C.; Musser, B.; Mallick, M.; Suryawanshi, S.; Maganti, L.; Zhu, H.; Han, T.H.; Scherer, L.; Simpson, B.; Cosgrove, D.; Gottesdiener, K.; Amatruda, J.; Rolls, B.J.; Blundell, J.; Bray, G.A.; Fujioka, K.; Heymsfield, S.B.; Wagner, J.A.; Herman, G.A. Potent and selective agonism of the melanocortin receptor 4 with MK-0493 does not induce weight loss in obese human subjects: energy intake predicts lack of weight loss efficacy. Clin Pharmacol Ther. 2009 Dec;86(6):659-666.
Kung, L.A.; Tao, S.C.; Qian, J.; Smith, M.G.; Snyder, M.; Zhu, H. Global analysis of the glycoproteome in Saccharomyces cerevisiae reveals new roles for protein glycosylation in eukaryotes. Mol Syst Biol. 2009;5:308.
Lin, Y.Y.; Lu, J.Y.; Zhang, J.; Walter, W.; Dang, W.; Wan, J.; Tao, S.C.; Qian, J.; Zhao, Y.; Boeke, J.D.; Berger, S.L.; Zhu, H. Protein acetylation microarray reveals that NuA4 controls key metabolic target regulating gluconeogenesis. Cell. 2009 Mar 20;136(6):1073-1084.
Zhang, J.; Sprung, R.; Pei, J.; Tan, X.; Kim, S.; Zhu, H.; Liu, C.F.; Grishin, N.V.; Zhao, Y. Lysine acetylation is a highly abundant and evolutionarily conserved modification in Escherichia coli. Mol Cell Proteomics. 2009 Feb;8(2):215-225.
Zhu, J.; Liao, G.; Shan, L.; Zhang, J.; Chen, M.R.; Hayward, G.S.; Hayward, S.D.; Desai, P.; Zhu, H. Protein array identification of substrates of the Epstein-Barr virus protein kinase BGLF4. J Virol. 2009 May;83(10):5219-5231.
Lin, J.; Xie, Z.; Zhu, H.; Qian, J. Understanding protein phosphorylation on a systems level. Brief Funct Genomics. 2010 Jan;9(1):32-42.
Selvin, E.; Steffes, M.W.; Zhu, H.; Matsushita, K.; Wagenknecht, L.; Pankow, J.; Coresh, J.; Brancati, F.L. Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. N Engl J Med. 2010 Mar 4;362(9):800-811.
Xie, Z.; Hu, S.; Blackshaw, S.; Zhu, H.; Qian, J. hPDI: a database of experimental human protein-DNA interactions. Bioinformatics. 2010 Jan 15;26(2):287-289.
Zhu, H.; Jones, C.K.; van Zijl, P.C.; Barker, P.B.; Zhou, J. Fast 3D chemical exchange saturation transfer (CEST) imaging of the human brain. Magn Reson Med. 2010 Sep;64(3):638-644.