NAME: Chen, Weilin

POSITION TITLE: Professor of Immunology, Shenzhen University School of Medicine

EDUCATION/TRAINING

INSTITUTION AND LOCATION	DEGREE	Completion Date MM/YYYY	FIELD OF STUDY
Zhejiang Medical University, Hangzhou, China	B. Med	06/1996	Public Health
Zhejiang University, Hangzhou, China	M.Sc.	06/1999	Public Health
Zhejiang University, Hangzhou, China	Ph.D.	06/2004	Oncology

 

A.   Personal Statement

I joined the institute of Immunology in Zhejiang University in 1999, received my Ph.D. in Oncology in 2004 and became Professor in 2013. In 2017, I moved to Shenzhen University as a Distinguished Professor of Immunology. My research is focused on the mechanisms of innate immunity, namely how an innate immune cell communicates with its surroundings and within itself. In particular, we are fascinated by how the cell detects pathogen-associated molecular patterns and mounts an appropriate innate immune response to restore the host defense.

 

B.   Positions and Honors

Positions and Employment

08/ 1999 — 12/ 2001    Research Associate , Institute of Immunology School of Medicine, Zhejiang       

                                    University, Hangzhou, China

 

12/2001 —12/ 2005     Assistant Professor , Institute of Immunology School of Medicine, Zhejiang       

                                    University, Hangzhou, China

 

07/2007 — 04/2009     Visiting S cholar , PHRI of UMDNJ , Newark, NJ, 07103, USA

 

12/2005 — 12/ 20 13      Associate Professor , Institute of Immunology School of Medicine, Zhejiang       

                                    University, Hangzhou, China

 

12/2013 — 03/ 20 17      Professor , Institute of Immunology School of Medicine, Zhejiang       

                                    University, Hangzhou, China

 

03/2017 – present       Professor, Shenzhen University School of Medicine, Shenzhen, China

 

Honors

1.    Outstanding Graduation Award of Zhejiang Province in the Undergraduate Program : 1996

2.    Graduation with Honor in the Doctoral Graduate Program of Zhejiang University: 20 04

3.    Chinese Government Scholarship Program, China Scholarship Council, Beijing: 20 07

4.    Advanced individual of caring about both career and family, Zhejiang University : 20 12

5.    Zhejiang University Quality Teaching Award, Second Prize: 201 3

6.    Young teacher teaching skills prize of Zhejiang University: 201 3

7.    Roche Diagnostics Research Award, Roche Diagnostics Greater China, Shanghai: 20 13

8.    Excellent teacher of Zhejiang University School of Medicine: 201 3

9.    Excellent Young Researcher Award, National Natural Science Foundation of China: 201 3

10.  Outstanding communist party member of Zhejiang University : 2013

 

C.   Contributions to Science (*: corresponding/co-corresponding author)

A full list of my publications is enclosed at the end of this document.

 

     1. Innate Immune Sensing and Immune Regulation

Innate immunity is the first line host defense against pathogen infection. Pattern recognition receptors (PRRs) including Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), C-type lectin receptors (CLRs) and Nod-like receptors (NLRs) are the main sensors of invading pathogens. Extensive interplay between PRRs and other pivotal immune mediators and receptors orchestrate the outcome of host innate immune defenses. The distinct classes of PRRs overlap in the spectrum of pathogen-associated molecular patterns (PAMPs) they recognize and cross-integrate their downstream signaling pathways. PRR signaling is also cross-modulated by signaling generated via other membrane-associated receptors. We focus on the cross-talk between PRRs in innate immune sensing and immune regulation. We found that Siglec-G-induced recruitment of SHP2 and the E3 ubiquitin ligase c-Cbl to RIG-I leads to RIG-I degradation via K48-linked ubiquitination at Lys813 by c-Cbl. (Cell, 2013). In 2016, my PhD student Xibao Zhao et al. found that c-Cbl could interact with IRF3 and identified that c-Cbl promoted K48-linked polyubiquitination and degradation of IRF3. (Cellular Signaling 2016).

 

1)    Chen W^＃, Han C^＃, Xie B^＃, Hu X, Yu Q, Shi L, Wang Q, Li D, Wang J, Zheng P, Liu Y, Cao X. Induction of Siglec-G by RNA Viruses Inhibits the Innate Immune Response by Promoting RIG-I Degradation. Cell. 2013 ;152(3):467-78.

2)    Zhao X, Zhu H, Yu J, Li H, Ge J, Chen W*. c-Cbl-mediated ubiquitination of IRF3 negatively regulates IFN-β production and cellular antiviral response. Cell Signal. 2016 ;28(11):1683-1693

 

    2.  Cancer immunology and immunotherapy

Cancer cells are often detected by the immune system, but most cancers evade an attack by the immune system. Our group’s research is focused on identifying the immune mechanisms that can prevent cancer formation and discover novel immunotherapy pathways. In our research of tumor immunity, we found that exosomes derived from heat-shocked lymphoma cells (HS-Exo) as a novel vesicle tumor vaccine could induce anti-tumor T cell immune response (Eur J Immunol，2006). We verified that Myricetin has anticancer activity in human T24 bladder cancer cells both in vitro and in vivo (Nutr Cancer, 2012). We also showed that UCH-L5 can inhibit migration and invasion of glioma cells by down-regulating SNRPF expression (Oncotarget, 2017).

 

1)    Chen W, Wang J, Shao C，Liu S，Yu Y，Wang Q, Cao X. Efficient induction of antitumor T cell immunity by exosomes derived from heat-shocked lymphoma cells. Eur. J. Immunol. 2006 ; 36 (6):1598-607

2)    Sun F, Zheng XY, Ye J, Wu TT, Wang JL, Chen W*. Potential anticancer activity of myricetin in human T24 bladder cancer cells both in vitro and in vivo. Nutr Cancer. 2012; 64(4):599-606.

3)    Jiafeng Ge, Weiwei Hu, Hui Zhou, Juan Yu, Chongran Sun and Weilin Chen*. Ubiquitin carboxyl-terminal hydrolase isozyme L5 inhibits human glioma cell migration and invasion via downregulating SNRPF. Oncotarget 2017;8(69):113635-113649.

 

    3. Development of novel anti- inflammatory compounds

In collaboration with Dr. Wei-lie Xiao’s Lab, we have identified natural compounds from Premna szemaoensis that are reactive against inflammatory macrophages. These novel compounds exhibit great potential as anti-inflammatory therapeutic agents.

 

1)    Xibao Zhao, Debing Pu, Zizhao Zhao, Huihui Zhu, Hongrui Li, Yaping Shen, Xingjie Zhang , Ruihan Zhang, Jianzhong Shen, Weilie Xiao * and Weilin Chen * . Teuvincenone F Suppresses LPS-Induced Inflammation and NLRP3 Inflammasome Activation by Attenuating NEMO Ubiquitination. Front. Pharmacol. 2017; 8:565.

 

D.   Research Support

      1. National Natural Science Foundation of China, 31670914             2017.1-2020.12   

          Title: USP39 regulates innate immune response and the potential molecular mechanism

          Total Support: ¥600,000   Principal Investigator

     2. National Natural Science Foundation of China-Outstanding youth funding, 81322042

         Title: Infection immunity/ Immune regulation 2014.1-2016.12  

         Total Support: ¥1000,000   Principal Investigator

     3. National Natural Science Foundation of China, 81273222

        Title: Siglec-G negatively regulates RNA virus-induced type I interferon production and the potential  molecular  mechanism 2013.1-2016.12   

        Total Support: ¥700,000   Principal Investigator

    4. National Natural Science Foundation of China, 3120068

        Title: The role of Src in PRRs mediated type I interferon production 2013.1-2015.12  

        Total Support: ¥250,000   Principal Investigator

    5. Fundamental Research Funds for the Central Universities, 2014XZZX003-33

        Title: The role of DCIR in innate anti-infection immune response 2014.1-2015.12 

        Total Support: ¥300,000   Principal Investigator    

    6. Src negatively regulates PRR-mediated activation of IRF3

  Fundamental Research Funds for the Central Universities, 2013QNA7010 2013.1-2014.12  

 Total Support: ¥80,000   Principal Investigator   

    7. Zhejiang University K.P.Chao’s High Technology Development Foundation

  Title: DCIR negatively regulates anti-fungi innate immunity 2013.10-2014.09 

  Total Support: ¥30,000   Principal Investigato

    8．Zhejiang Provincial Natural Science Foundation of China, Y2110255

         Title: Src negatively regulates RNA virus-induced type I interferon production 2011.1-2013.12  

         Total Support: ¥90,000    Principal Investigator

     9. Traditional Medicine Office Foundation of Zhejiang Province, G20050546

         Title: Sinomenine-induced apoptosis of macrophages 2006.1-2008.12  

         Total Support: ¥100,000    Principal Investigator

     10. National Natural Science Foundation of China, N30371617

          Title: Study anti-tumor immunity mechanisms of newly effective antigen presenting bodies    

           2004.1-2006.12 

          Total Support: ¥200,000    Principal Investigator

 

E.    Peer-reviewed publications (*: corresponding author)

1. Jiafeng Ge, Weiwei Hu, Hui Zhou, Juan Yu, Chongran Sun and Weilin Chen*. Ubiquitin carboxyl-terminal hydrolase isozyme L5 inhibits human glioma cell migration and invasion via downregulating SNRPF. Oncotarget 2017;8(69):113635-113649.

2. Xibao Zhao, Debing Pu, Zizhao Zhao, Huihui Zhu, Hongrui Li, Yaping Shen, Xingjie Zhang , Ruihan Zhang, Jianzhong Shen, Weilie Xiao * and Weilin Chen * . Teuvincenone F Suppresses LPS-Induced Inflammation and NLRP3 Inflammasome Activation by Attenuating NEMO Ubiquitination. Front. Pharmacol. 2017; 8:565

3. Zhao X, Zhu H, Yu J, Li H, Ge J, Chen W*. c-Cbl-mediated ubiquitination of IRF3 negatively regulates IFN-β production and cellular antiviral response. Cell Signal. 2016 ;28(11):1683-1693

4. Zhao X, Shen Y, Hu W, Chen J, Wu T, Sun X, Yu J, Wu T, Chen W*. DCIR negatively regulates CpG-ODN-induced IL-1β and IL-6 production. Mol Immunol. 2015; 68(2):641-647

5. Chen W^＃, Han C^＃, Xie B^＃, Hu X, Yu Q, Shi L, Wang Q, Li D, Wang J, Zheng P, Liu Y, Cao X. Induction of Siglec-G by RNA Viruses Inhibits the Innate Immune Response by Promoting RIG-I Degradation. Cell. 2013 ;152(3):467-78.

6. Lai L, Song Y, Liu Y, Chen Q, Han Q, Chen W, Pan T, Zhang Y, Cao X, Wang Q. MicroRNA-92a negatively regulates TLR-triggered inflammatory response in macrophages by targeting MKK4. J Biol Chem. 2013 ; 288 (11):7956-67.

7.Sun F, Zheng XY, Ye J, Wu TT, Wang JL, Chen W*. Potential anticancer activity of myricetin in human T24 bladder cancer cells both in vitro and in vivo. Nutr Cancer. 2012; 64(4):599-606. 

8.Wang D, Lou J, Ouyang C, Chen W, Liu Y, Liu X, Cao X, Wang J, Lu L. Ras-related protein Rab10 facilitates TLR4 signaling by promoting replenishment of TLR4 onto the plasma membrane. Proc Natl Acad Sci U S A. 2010; 107 (31):13806-11.

9.Chen W, Wang J, Shao C，Liu S，Yu Y，Wang Q, Cao X. Efficient induction of antitumor T cell immunity by exosomes derived from heat-shocked lymphoma cells. Eur. J. Immunol. 2006 ; 36 (6):1598-607

10.Chen W, Wang J, An H，Zhou J，Zhang L，Cao X. Heat shock up-regulates TLR9 expression in human B cells through activation of ERK and NF-kappaB signal pathways, Immunol Lett. 2005；(98)1:153-159.

11. Chen W, Yu Y, Shao C, Zhang M, Wang W, Zhang L, Cao X. Enhancement of antigen-presenting ability of B lymphoma cells by immunostimulatory CpG-oligonucleotides and anti-CD40 antibody. Immunol Lett. 2001;77(1):17-23.

12. Guo ZH, Zhang MH, An HZ, Chen WL, Liu SX, Guo J, Yu YZ, Cao XT. Fas ligation IL-1beta-dependent maturation and IL-1beta-independent survival of dendritic cell: different roles of ERK and NF-κB singaling pathways. Blood.2003;102:4441-4447.

13.He J, Chen W, Jin L, Jin H. Comet assay and cytokinesis-blocked micronucleus test for monitoring the genotoxic effects of X-ray radiation in humans. Chin Med J (Engl). 2000; 113 (10): 911-4.

14. He JL, Chen WL, Jin LF, Jin HY. Comparative evaluation of the in vitro micronucleus test and the comet assay for the detection of genotoxic effects of X-ray radiation. Mutat Res. 2000; 469(2): 223-31.