Work Phone Number:
Los Angeles, CA 90095
|Member, Brain Research Institute, CTSI, JCCC Signal Transduction and Therapeutics Program Area, Molecular Biology Institute, Stein Eye Institute|
|Faculty, Cell & Developmental Biology GPB Home Area, Computational and Systems Biology Interdepartmental Program|
Our current research is at the interface of chemical biology, computational biology, structural biology, systems biology, and therapeutic development. To better understand the biological functions of different signaling pathways in the visual system and to explore the therapeutic potential of targeting abnormal signaling pathways. The current focus of our laboratory is structure-based drug discovery with an emphasis on developing proteins and small molecules that can systematically modulate signal transduction pathways. In an effort of translational research, our laboratory is also interested in structure-based drug repositioning.
Currently, the Wnt pathway is one of the focuses in our laboratory. Wnt signaling plays an essential role in embryonic development and regulation of cell growth. Inappropriate activation of the Wnt pathway has been shown to lead to different eye diseases, including glaucoma, degenerative retinal disorders, and corneal diseases. Aiming to develop potential novel pharmaceutical agents, we have taken a systems biology approach and are working on the development of small-molecule inhibitors that target different protein-protein interactions alone the Wnt signaling pathways.
Diouf Barthelemy, Lin Wenwei, Goktug Asli, Grace Christy R R, Waddell Michael Brett, Bao Ju, Shao Youming, Heath Richard J, Zheng Jie J, Shelat Anang A, Relling Mary V, Chen Taosheng, Evans William E Alteration of RNA Splicing by Small-Molecule Inhibitors of the Interaction between NHP2L1 and U4. SLAS discovery : advancing life sciences R & D. 2017; 2472555217735035.
Zhang Chi, Miller Darcie J, Guibao Cristina D, Donato Dominique M, Hanks Steven K, Zheng Jie J Structure-functional insights into the interaction between the Cas family scaffolding protein p130Cas and the focal adhesion-associated protein paxillin. The Journal of biological chemistry. 2017; .
Yang Jun, Milasta Sandra, Hu Dongli, AlTahan Alaa, Interiano Rodrigo, Zhou Junfang, Davidson Jesse, Low Jonathan, Lin Wenwei, Bao Ju, Goh Pollyanna, Nathwani Amit, Wang Ruoning, Wang Yingdi, Ong Su Sien, Boyd Vincent, Young Brandon, Das Sourav, Shelat Anang A, Wu Yinan, Li Zhenmei, Zheng Jie, Mishra Ashutosh, Cheng Yong, Qu Chunxu, Peng Junmin, Green Douglas R, White Stephen, Guy R Kip, Chen Taosheng, Davidoff Andrew Targeting histone demethylases in MYC-driven neuroblastomas with ciclopirox. Cancer research. 2017; 12(7): e0180366.
Ahadome Sarah D, Zhang Chi, Tannous Elizabeth, Shen James, Zheng Jie J Small-molecule inhibition of Wnt signaling abrogates dexamethasone-induced phenotype of primary human trabecular meshwork cells. Experimental cell research. 2017; 90(8): 562-574.
Qi Jing, Lee Ho-Jin, Saquet Audrey, Cheng Xiao-Ning, Shao Ming, Zheng Jie J, Shi De-Li Auto-inhibition of Dishevelled regulated by its extreme C-terminus plays a distinct role in Wnt/beta-catenin and Wnt/PCP signaling pathways. The Journal of biological chemistry. 2017; 167: 26-30.
Tran Freddi Huan, Zheng Jie J Modulating the Wnt signaling pathway with small molecules. Protein science : a publication of the Protein Society. 2017; .
Bao Ju, Marathe Bindumadhav, Govorkova Elena A, Zheng Jie J Drug Repurposing Identifies Inhibitors of Oseltamivir-Resistant Influenza Viruses. Angewandte Chemie (International ed. in English). 2016; 128(10): 3499–3502.
Young Alejandra, Dandekar Uma, Pan Calvin, Sader Avery, Zheng Jie J, Lewis Richard A, Farber Debora B GNAI3: Another Candidate Gene to Screen in Persons with Ocular Albinism. PloS one. 2016; 11(9): e0162273.
Bari Rafijul, Thapa Rajoo, Bao Ju, Li Ying, Zheng Jie, Leung Wing KIR2DL2/2DL3-E(35) alleles are functionally stronger than -Q(35) alleles. Scientific reports. 2016; 6(1): 23689.
Vanarotti Murugendra S, Finkelstein David B, Guibao Cristina D, Nourse Amanda, Miller Darcie J, Zheng Jie J Structural basis for the interaction between Pyk2-FAT domain and Leupaxin LD repeats. Biochemistry. 2016; 146: .
Morgan Jessica A, Lynch John, Panetta John C, Wang Yao, Frase Sharon, Bao Ju, Zheng Jie, Opferman Joseph T, Janke Laura, Green Daniel M, Chemaitilly Wassim, Schuetz John D Apoptosome activation, an important molecular instigator in 6-mercaptopurine induced Leydig cell death. Scientific reports. 2015; 5: 16488.
Diouf Barthelemy, Crews Kristine R, Lew Glen, Pei Deqing, Cheng Cheng, Bao Ju, Zheng Jie J, Yang Wenjian, Fan Yiping, Wheeler Heather E, Wing Claudia, Delaney Shannon M, Komatsu Masaaki, Paugh Steven W, McCorkle Joseph Robert, Lu Xiaomin, Winick Naomi J, Carroll William L, Loh Mignon L, Hunger Stephen P, Devidas Meenakshi, Pui Ching-Hon, Dolan M Eileen, Relling Mary V, Evans William E Association of an inherited genetic variant with vincristine-related peripheral neuropathy in children with acute lymphoblastic leukemia. JAMA. 2015; 313(8): 815-23.
Lee Ho-Jin, Shi De-Li, Zheng Jie J Conformational change of Dishevelled plays a key regulatory role in the Wnt signaling pathways. eLife. 2015; 4: e08142.
Lee Ho-Jin, Bao Ju, Miller Ami, Zhang Chi, Wu Jibo, Baday Yiressy C, Guibao Cristina, Li Lin, Wu Dianqing, Zheng Jie J Structure-based discovery of novel small molecule Wnt signaling inhibitors by targeting the cysteine rich domain of Frizzled. The Journal of biological chemistry. 2015; 290(51): 30596-606.
Brown Nicholas G, Watson Edmond R, Weissmann Florian, Jarvis Marc A, VanderLinden Ryan, Grace Christy R R, Frye Jeremiah J, Qiao Renping, Dube Prakash, Petzold Georg, Cho Shein Ei, Alsharif Omar, Bao Ju, Davidson Iain F, Zheng Jie J, Nourse Amanda, Kurinov Igor, Peters Jan-Michael, Stark Holger, Schulman Brenda A Mechanism of polyubiquitination by human anaphase-promoting complex: RING repurposing for ubiquitin chain assembly. Molecular cell. 2014; 56(2): 246-60.
Vanarotti Murugendra S, Miller Darcie J, Guibao Cristina D, Nourse Amanda, Zheng Jie J Structural and mechanistic insights into the interaction between Pyk2 and paxillin LD motifs. Journal of molecular biology. 2014; 426(24): 3985-4001.
Bao Ju, Lee Ho-Jin, Zheng Jie J Genome-wide network analysis of Wnt signaling in three pediatric cancers. Scientific reports. 2013; 3(2): 2969.
Rana Rajashree, Carroll Candace E, Lee Ho-Jin, Bao Ju, Marada Suresh, Grace Christy R R, Guibao Cristina D, Ogden Stacey K, Zheng Jie J Structural insights into the role of the Smoothened cysteine-rich domain in Hedgehog signalling. Nature communications. 2013; 4(2): 2965.
Li Xiaofeng, Shan Jufang, Chang Woochul, Kim Ingyu, Bao Ju, Lee Ho-Jin, Zhang Xinxin, Samuel Varman T, Shulman Gerald I, Liu Dakai, Zheng Jie J, Wu Dianqing Chemical and genetic evidence for the involvement of Wnt antagonist Dickkopf2 in regulation of glucose metabolism. Proceedings of the National Academy of Sciences of the United States of America. 2012; 109(28): 11402-7.
Shan Jufang, Zhang Xinxin, Bao Ju, Cassell Robert, Zheng Jie J Synthesis of potent dishevelled PDZ domain inhibitors guided by virtual screening and NMR studies. Chemical biology & drug design. 2012; 79(4): 376-83.
Bao Ju, Zheng Jie J, Wu Dianqing The structural basis of DKK-mediated inhibition of Wnt/LRP signaling. Science signaling. 2012; 5(224): pe22.
Shan Jufang, Zheng Jie J Virtual ligand screening combined with NMR to identify Dvl PDZ domain inhibitors targeting the Wnt signaling. Methods in molecular biology (Clifton, N.J.). 2012; 928(4): 17-28.
Alli Rajshekhar, Zhang Ziwei M, Nguyen Phuong, Zheng Jie J, Geiger Terrence L Rational design of T cell receptors with enhanced sensitivity for antigen. PloS one. 2011; 6(3): e18027.
Bari Rafijul, Guo Qiusha, Xia Bing, Zhang Yanhui H, Giesert Eldon E, Levy Shoshana, Zheng Jie J, Zhang Xin A Tetraspanins regulate the protrusive activities of cell membrane. Biochemical and biophysical research communications. 2011; 415(4): 619-26.
Lee Ho-Jin, Finkelstein David, Li Xiaofeng, Wu Dianqing, Shi De-Li, Zheng Jie J Identification of transmembrane protein 88 (TMEM88) as a dishevelled-binding protein. The Journal of biological chemistry. 2010; 285(53): 41549-56.
Lin Shuei-Liong, Li Bing, Rao Sujata, Yeo Eun-Jin, Hudson Thomas E, Nowlin Brian T, Pei Huaying, Chen Lijun, Zheng Jie J, Carroll Thomas J, Pollard Jeffrey W, McMahon Andrew P, Lang Richard A, Duffield Jeremy S Macrophage Wnt7b is critical for kidney repair and regeneration. Proceedings of the National Academy of Sciences of the United States of America. 2010; 107(9): 4194-9.
Lee Ho-Jin, Zheng Jie J PDZ domains and their binding partners: structure, specificity, and modification. Cell communication and signaling : CCS. 2010; 8(53): 8.
Wang Nick X, Zheng Jie J Computational studies of H5N1 influenza virus resistance to oseltamivir. Protein science : a publication of the Protein Society. 2009; 18(4): 707-15.
Grandy David, Shan Jufang, Zhang Xinxin, Rao Sujata, Akunuru Shailaja, Li Hongyan, Zhang Yanhui, Alpatov Ivan, Zhang Xin A, Lang Richard A, Shi De-Li, Zheng Jie J Discovery and characterization of a small molecule inhibitor of the PDZ domain of dishevelled. The Journal of biological chemistry. 2009; 284(24): 16256-63.
Lee Ho-Jin, Wang Nick X, Shao Youming, Zheng Jie J Identification of tripeptides recognized by the PDZ domain of Dishevelled. Bioorganic & medicinal chemistry. 2009; 17(4): 1701-8.
Shan Jufang, Zheng Jie J Optimizing Dvl PDZ domain inhibitor by exploring chemical space. Journal of computer-aided molecular design. 2009; 23(1): 37-47.
Wu Bai-Nan, Zhang Yong-Mei, Rock Charles O, Zheng Jie J Structural modification of acyl carrier protein by butyryl group. Protein science : a publication of the Protein Society. 2009; 18(1): 240-6.
Lee Ho-Jin, Wang Nick X, Shi De-Li, Zheng Jie J Sulindac inhibits canonical Wnt signaling by blocking the PDZ domain of the protein Dishevelled. Angewandte Chemie (International ed. in English). 2009; 48(35): 6448-52.
Bari Rafijul, Zhang Yanhui H, Zhang Feng, Wang Nick X, Stipp Christopher S, Zheng Jie J, Zhang Xin A Transmembrane interactions are needed for KAI1/CD82-mediated suppression of cancer invasion and metastasis. The American journal of pathology. 2009; 174(2): 647-60.
Xing Yi, Takemaru Ken-Ichi, Liu Jing, Berndt Jason D, Zheng Jie J, Moon Randall T, Xu Wenqing Crystal structure of a full-length beta-catenin. Structure (London, England : 1993). 2008; 16(3): 478-87.
Zhang Ziwei M, Simmerman Joseph A, Guibao Cristina D, Zheng Jie J GIT1 paxillin-binding domain is a four-helix bundle, and it binds to both paxillin LD2 and LD4 motifs. The Journal of biological chemistry. 2008; 283(27): 18685-93.
Bertolucci Craig M, Guibao Cristina D, Zheng Jie J Phosphorylation of paxillin LD4 destabilizes helix formation and inhibits binding to focal adhesion kinase. Biochemistry. 2008; 47(2): 548-54.
Chen Lijun, Wang Ke, Shao Youming, Huang Jin, Li Xiaofeng, Shan Jufang, Wu Dianqing, Zheng Jie J Structural insight into the mechanisms of Wnt signaling antagonism by Dkk. The Journal of biological chemistry. 2008; 283(34): 23364-70.
Wang Nick X, Lee Ho-Jin, Zheng Jie J Therapeutic use of PDZ protein-protein interaction antagonism. Drug news & perspectives. 2008; 21(3): 137-41.