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*, Lvqin Zheng*, Jianquan Lin*, Bailing Zhang, Yuwei Zhu, Ningning Li , Shuangyu Xie, Yuhang Wang, Ning Gao#, Zhiwei Huang# (2019). Structural basis of assembly of the human T cell receptor-CD3 complex. Nature.573(7775):546-552. (This paper is featured with News & Views, Nature. 573, 502-504 (2019))

2.Liyong Dong*, Xiaoyu Guan*, Ningning Li*, Fan Zhang, Yuwei Zhu, Kuan Ren, Ling Yu, Fengxia Zhou, Zhifu Han, Ning Gao & Zhiwei Huang# (2019). An anti-CRISPR protein disables type V Cas12a by acetylation. Nature Structural & Molecular Biology. 26(4):308-314.

3.Minghui Guo*, Kaiming Zhang*, Yuwei Zhu, Grigore D. Pintilie, Xiaoyu Guan, Shanshan Li, Michael F. Schmid, Zhuo Ma, Wah Chiu# & Zhiwei Huang#(2019). Coupling of ssRNA Cleavage with DNase Activity in Type III-A CRISPR-Csm Revealed by Cryo-EM and Biochemistry. Cell Research. 29(4):305-312.

4.Minghui Guo*, Kuan Ren*, Yuwei Zhu*, Ziyun Tang, Yuhang Wang, Bailing Zhang & Zhiwei Huang# (2019). Structural insights into a high fidelity variant of SpCas9. Cell Research. 29,183-192.

5.Yuwei Zhu, Zhiwei Huang# (2018). Recent advances in structural studies of the CRISPR-Cas-mediated genome editing tools. National Science Review. doi: 10.1093/nsr/nwy150

6.Liuke Sun, Ruifang Shen, Sandeep K. Agnihotri, Yun Chen, Zhiwei Huang & Hansruedi Büeler# (2018). Lack of PINK1 alters glia innate immune responses and enhances inflammation-induced, nitric oxide-mediated neuron death. Scientific Reports. 8(1):383.

7.Fan Zhang#, Shijia Zhao, Chunyan Ren, Yuwei Zhu, Haibin Zhou, Yongkui Lai, Fengxia Zhou, Yuqiang Jia, Kangjie Zheng & Zhiwei Huang# (2018). CRISPRminer is a knowledge base for exploring CRISPR-Cas systems in microbe and phage interactions. Communications Biology. 31;1:180.

8.De Dong*, Minghui Guo*, Sihan Wang*, Yuwei Zhu, Shuo Wang,Zhi Xiong, Jianzheng Yang, Zengliang Xu and Zhiwei Huang# (2017). Structural basis of CRISPR-SpyCas9 inhibition by an anti-CRISPR protein. Nature. 546(7658):436-439.

9.Dan Wu*, Xiaoyu Guan*, Yuwei Zhu*, Kuan Ren, Zhiwei Huang# (2017). Structural basis of stringent PAM recognition by CRISPR-C2c1 in complex with sgRNA.Cell Research. 27(5):705-708.

10.Marchisio# & Zhiwei Huang# (2017). CRISPR-Castype II-based Synthetic Biology applications in eukaryotic cells. RNA Biology. 14(10):1286-1293.

11.Pu Gao, Hui Yang, Kanagalaghatta R Rajashankar, Zhiwei Huang and Dinshaw J Patel (2016). Type V CRISPR-Cas Cpf1 endonuclease employs a unique mechanism for crRNA-mediated target DNA recognition. Cell Research. 26(8):901-13.

12.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(7600):522-6.

13.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(7482):229-33. (This paper is featured with News & Views, Nature. 505, 167-168, highlighted in Nature Structural & Molecular Biology, 21, 117 (2014))

14.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. 123(9):4010-22.

15.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. 341(6142):172-5.

16.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(1):59-65.

17.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. 49(4):164-73.

18.Zhiwei Huang and Jijie Chai (2010). Mapping the selection mechanisms by bacterial GEFs. Virulence. 1(2):93-6.

19.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):853-60. (This publication was selected as cover story, and high-lighted by Nature China）

20.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):529-42. (This publication was selected as a research “highlight” by Nature China）

21.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):434-46.