Research Description
We use multi-disciplinary approaches including structural biology, biochemistry, virology, cell biology, and mouse genetics in our studies. Our research interests focus on:
1). Investigates the structure-function relationships of macromolecules (soluble & membrane proteins) of interest in the field of immunology and infectious diseases. Our research focus on understanding the molecular basis of important pathogen-host interactions. We are interested in studying structure-function relationship of soluble/membrane protein complexes involved in immunology and infectious diseases signaling pathways and using structural information to rational design therapeutic agents for the treatment of diseases.
2). Studies the molecular mechanisms of CRISPR-Cas systems. Most of archaea and many bacteria encode a diverse set of CRISPR-Cas systems as an adaptive immune system to defend themselves against phage infection. After integration of short segments of invader-derived DNAs (or RNAs in some cases) into a CRISPR array within the host genome, expression and processing of the precursor CRISPR RNAs (crRNAs) produces mature crRNAs. The mature crRNAs then guide an effector protein or a Cas protein complex, to target and cleave foreign DNAs (or RNAs in some cases) bearing complementary sequences. We are interested in figuring out how CRISPR-Cas systems work, and engineering CRISPR-Cas systems for precisely genome editing applications.
3). Identifies regulators and signal transduction events involved in cell death during HIV or bacterial infection. Pyroptosis is triggered by various pathological stimuli, such as pathogen infection, which is important for controlling microbial infection. But it is largely unknown for the mechanism on this pathogen-induced lytic form of cell death. Our efforts are focused on identifying novel signaling components and signaling pathways in pyroptosis.
Publications (* Co-first author, # Corresponding author）
1.De Dong*, Kuan Ren*, Xiaolin Qiu*, Jianlin Zheng, Minghui Guo, Xiaoyu Guan, Hongnan Liu, Ningning Li, Bailing Zhang, Daijun Yang, Chuang Ma, Shuo Wang, Dan Wu, Yunfeng Ma, Shilong Fan, Jiawei Wang, Ning Gao and Zhiwei Huang#（2016）. Crystal structure of CRISPR-Cpf1 in complex with CRISPR RNA (crRNA). Nature. 532, 522-526.
2.Yingying Guo*, Liyong Dong*, Xiaolin Qiu*, Yishu Wang, Bailing Zhang, Hongnan Liu, You Yu, Yi Zang, Maojun Yang and Zhiwei Huang# (2014). Structural basis for hijacking CBF-β and CUL5 E3 ligase complex by HIV-1 Vif. Nature. 505, 229-233. (This paper is featured with News & Views, Nature. 505, 167-168, highlighted in Nature Structural & Molecular Biology, 21, 117 (2014))
3.Jae-Hyuck Shim, Matthew B. Greenblatt, Weiguo Zou, Zhiwei Huang, Marc N. Wein, Nicholas Brady, Dorothy Hu, Jean Charron, Heather R. Brodkin, Gregory A. Petsko, Dennis Zaller, Bo Zhai, Steven Gygi, Laurie H. Glimcher and Dallas C. Jones (2013). Schnurri-3 regulates ERK downstream of WNT signaling in osteoblasts. J Clin Invest. doi:10.1172/JCI69443.
4.Zehan Hu, Chuangye Yan, Peiyuan Liu, Zhiwei Huang, Rui Ma, Chenlu Zhang, Ruiyong Wang, Yueteng Zhang, Fabio Martinon, Di Miao, Haiteng Deng, Jiawei Wang, Junbiao Chang, Jijie Chai (2013). Crystal structure of NLRC4 reveals its autoinhibition mechanism. Science. 12, 172-175.
5.Weiguo Zou, Xi Chen, Jae Shim, Zhiwei Huang, Nicholas Brady, Dorothy Hu, Rebecca Drapp, Kirsten Sigrist, Laurie H. Glimcher, Dallas Jones (2011). The E3 ubiquitin ligase Wwp2 regulates craniofacial development through monoubiquitination of Goosecoid. Nature Cell Biology. 13, 59-65.
6.Chen D, Lei L, Flores R, Zhiwei Huang, Wu Z, Chai J, Zhong G. (2010). Autoprocessing and self-activation of the secreted protease CPAF in Chlamydia-infected cells. Microbial Pathogenesis. 1(10), 1-10.
7.Zhiwei Huang and Jijie Chai (2010). Mapping the selection mechanisms by bacterial GEFs. Virulence. 1(2), 1-4.
8.Zhiwei Huang*, Sarah E. Sutton*, Adam J. Wallenfang, Robert C. Orchard, Xiaojing Wu, Yingcai Feng, Jijie Chai and Neal M. Alto (2009). Structural insights into host GTPase isoform selection by a family of bacterial GEF mimics. Nature Structural & Molecular Biology. 16(8), 853 – 860. (This publication was selected as cover story, and highlighted by Nature China）
9.Zhiwei Huang, Yingcai Feng, Ding Chen, Xiaojing Wu, Xiaojun Wang, Xingguo Xiao, Wenhui Li, Niu Huang, Lichuan Gu, Guangming Zhong and Jijie Chai (2008). Structural basis for activation and inhibition of the secreted chlamydia protease CPAF. Cell Host & Microbe. 4(6), 529-542. (This publication was selected as a research “highlight” by Nature China）
10.Maikke B. Ohlson, Zhiwei Huang, Neal M. Alto, Jack E. Dixon, Jijie Chai and Samuel I. Miller (2008). Structure and Function of Salmonella SifA Indicate that Its Interactions with SKIP, SseJ, and RhoA Family GTPases Induce Endosomal Tubulation. Cell Host & Microbe. 4(5), 434-446