BIOGRAPHICAL SKETCH

NAME: Xinchun Chen

POSITION TITLE: Distinguished Professor, Vice Director of Shenzhen University Health Science Center, Dean of School of Basic Medical Sciences.

EDUCATION/TRAINING:

A. Personal Statement

I have been working in the field of tuberculosis (TB) for >16 years, first as clinical physician specializing in TB and subsequently also as immunologist for basic research in TB. My research has focused on human immunity to TB with a long-term goal of developing novel diagnostic biomarkers and/or novel candidate molecules for TB prevention or treatment. While it is our advantage to characterize the immune profile of human TB patients and dissect the key mechanism for TB, I welcome the opportunity to translate research findings from animal models to our clinical population and to “back-translate” clinical findings into animals. It is hoped that this approach will lead to more predictive, targeted and interpretable animal models of various stages of TB infection and disease.

B. Positions and Honors

1992-1995       Physician, Jiangxi Xinhua Hospital

1998-2002       Attending Doctor, Dept. tuberculosis, Shenzhen Donghu Hospital

2006-2009       Associate Professor and associate Director, Shenzhen-Hong Kong Institute of Infectious Disease

2010-2016       Professor and Associate Director, Shenzhen-Hong Kong Institute of Infectious Disease, Shenzhen Third People’s Hospital

2016-present       Distinguished Professor, Head of Department of Pathogen Biology, Associate Dean, School of Basic Medicine, Shenzhen University School of Medicine

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

1. Zhang G, deWeerd NA, Stifter SA, Liu L, Zhou B, Wang W, Zhou Y, Ying B, Hu X, Matthews AY, Ellis M, Triccas JA, Hertzog PJ, Britton WJ, Chen X*, Feng CG*. A proline deletion in IFNAR1 impairs IFN-signaling and underlies increased resistance to tuberculosis in humans. Nat Commun. 2018 Jan 8;9(1):85.

2. Zeng G*, Zhang G*, Chen X*. Th1 cytokines, true functional signatures for protective immunity against TB?Cell Mol Immunol. 2018 Mar;15(3):206-215.

3. Liu X, Hou XF, Gao L, Deng GF, Zhang MX, Deng QY, Ye TS, Yang QT, Zhou BP, Wen ZH, Liu HY, Kornfeld H, Chen XC*. Indicators for prediction of Mycobacterium tuberculosis positivity detected with bronchoalveolar lavage fluid. Infect Dis Poverty. 2018 Mar 24;7(1):22

4. Rothchild AC, Stowell B, Goyal G, Nunes-Alves C, Yang Q, Papavinasasundaram K, Sassetti CM, Dranoff G, Chen X, Lee J, Behar SM. Role of Granulocyte-Macrophage Colony-Stimulating Factor Production by T Cells during Mycobacterium tuberculosis Infection. MBio. 2017 Oct 24;8(5). pii: e01514-17

5. Mishra BB, Lovewell RR, Olive AJ, Zhang G, Wang W, Eugenin E, Smith CM, Phuah JY, Long JE, Dubuke ML, Palace SG, Goguen JD, Baker RE, Nambi S, Mishra R, Booty MG, Baer CE, Shaffer SA, Dartois V, McCormick BA, Chen X*, Sassetti CM*.  Nitric oxide prevents a pathogen-permissive granulocytic inflammation during tuberculosis. Nat Microbiol. 2017 May 15;2:17072

6. Zhang G, Liu X, Wang W, Cai Y, Li S, Chen Q, Liao M, Zhang M, Zeng G, Zhou B, Feng CG, Chen X*.Down-regulation of miR-20a-5p triggers cell apoptosis to facilitate mycobacterial clearance through targeting JNK2 in human macrophages. Cell Cycle. 2016 Sep 16;15(18):2527-38.

7. Jiang J, Chen X* An H, Yang B, Zhang F, Cheng X*. Enhanced immune response of MAIT cells in tuberculous pleural effusions depends on cytokine signaling. Sci Rep. 2016 Sep 2;6:32320. doi: 10.1038/srep32320.

8. Cai Y, Yang Q, Liao M, Wang H, Zhang C, Nambi S, Wang W, Zhang M, Wu J, Deng G, Deng Q, Liu H, Zhou B, Jin Q, Feng CG, Sassetti CM, Wang F, Chen X*. xCT increases tuberculosis susceptibility by regulating antimicrobial function and inflammation. Oncotarget. 2016 May 24;7(21):31001-13

9. Yang Q, Xu Q, Chen Q, Li J, Zhang M, Cai Y, Liu H, Zhou Y, Deng G, Deng Q, Zhou B, Kornfeld H, Chen X*.Discriminating Active Tuberculosis from Latent Tuberculosis Infection by flow cytometric measurement of CD161-expressing T cells. Sci Rep. 2015 Dec 8;5:17918. doi: 10.1038/srep17918.

10. Torrado E, Fountain JJ, Liao M, Tighe M, Reiley WW, Lai RP, Meintjes G, Pearl JE, Chen X, Zak DE, Thompson EG, Aderem A, Ghilardi N, Solache A, McKinstry KK, Strutt TM, Wilkinson RJ, Swain SL, Cooper AM. Interleukin 27R regulates CD4+ T cell phenotype and impacts protective immunity during Mycobacterium tuberculosis infection. J Exp Med. 2015 Aug 24;212(9):1449-63.

11. Yu Y, Jin D, Hu S, Zhang Y, Zheng X, Zheng J, Liao M, Chen X, Graner M, Liu H*, Jin Q*. A novel tuberculosis antigen identified from human tuberculosis granulomas. Mol Cell Proteomics. 2015 Apr;14(4):1093-103.

12. Yang Q, Cai Y, Zhao W, Wu F, Zhang M, Luo K, Zhang Y, Liu H, Zhou B, Kornfeld H, Chen X*.IP-10 and MIG Are Compartmentalized at the Site of  Disease during Pleural  and Meningeal Tuberculosis and Are Decreased after Antituberculosis Treatment. Clin Vaccine Immunol. 2014 Dec;21(12):1635-44. doi: 10.1128/CVI.00499-14.

13. Zhang G, Zhou B, Li S, Yue J, Yang H, Wen Y, Zhan S, Wang W, Liao M, Zhang M, Zeng G, Feng CG, Sassetti CM*, Chen X*. Allele-Specific Induction of IL-1b Expression by C/EBPb and PU.1 Contributes to Increased Tuberculosis Susceptibility. PLoS Pathogens, 2014 Oct 16;10(10):e1004426.

14. Ma J, Yang B, Yu S, Zhang Y, Zhang X, Lao S, Chen X, Li B, Wu C. Tuberculosis antigen-induced expression of IFN-α in tuberculosis patients inhibits production of IL-1β. FASEB J. 2014; Mar 27 [Epub ahead of print].

15. Cai Y, Yang Q, Tang Y, Zhang M, Liu H, Zhang G, Huang J, Gao Z, Zhou B, Feng CG, Chen X *. Increased complement C1q level marks active disease in human tuberculosis. PLoS One. 2014; 9(3):e92340.

16. Zhang M, Zhang G, Yang Q, Zhang J, Zhu X, Chen Q, Suthakaran P, Zhang Y, Deng, Q, Liu H, Zhou B, Chen X *.Anti-tuberculosis treatment enhances the production of IL-22 through reducing the frequencies of regulatory B cell.Tuberculosis 2014; 94:238-244.

17. Liu L, Zhang WJ, Zheng J, Fu H, Chen Q, Zhang Z, Chen X, Zhou B, Feng L, Liu H, Jin Q. xploration of novel cellular and serological antigen biomarkers in the ORFeome of Mycobacterium tuberculosis. Mol Cell Proteomics. 2014 ; 13(3) :897-906.

18. Liao M, Yang Q, Zhang J, Zhang M, Deng Q, Liu H, Garner MW, Kornfeld H, Chen X *. Gamma interferon immunospot assay of pleural effusion mononuclear cells for diagnosis of tuberculous pleurisy. Clin Vaccine Immunol. 2014; 21(3):347-353.

19. Zhang G, Zhou B, Wang W, Zhang M, Zhao Y, Wang Z, Yang L, Zhai J, Feng CG, Wang J, Chen X *. A Functional Single-Nucleotide Polymorphism in Interleukin-6 Promoter is associated with Susceptibility to Tuberculosis. J Infect Dis. 2012; 205(11):1697-704.

20. Zhang M, Zheng X, Zhang J, Zhu Z, Zhu X, Liu H, Zeng M, Graner WM, Zhou B, Chen X*. CD19+CD1d+CD5+ B Cell Frequencies Are Increased in Patients with Tuberculosis and Suppress Th17 Responses. Cell Immunol. 2012; 274(1-2):89-97.

21. Qiu Z, Zhang M,Zhu Y,Zheng F,Lu P,Liu H, Graner WM, Zhou B, Chen X *. Multifunctional CD4 T Cell Responses in Patients with Active Tuberculosis. Multifunctional CD4 T Cell Responses in Patients with Active Tuberculosis. Sci. Rep. 2012; 2( 216); DOI:10.1038/srep00216.

22. Zhang G#, Chen X#, Chan L , Zhang M1, Zhu B , Wang L, Zhu X, Zhang J, Zhou B, Wang J. An SNP selection strategy identified IL-22 associating with susceptibility to tuberculosis in Chinese. Sci. Rep. 2011，1(20); DOI:10.1038/srep00020. (#equally contributed)

23. Zhang M, Wang Z, Graner MW, Yang L, Liao M, Yang Q, Gou J, Zhu Y, Wu C, Liu H, Zhou B, Chen X*. B cell infiltration is associated with the increased IL-17 and IL-22 expression in the lungs of patients with tuberculosis. Cell Immunol. 2011; 270(2):217-23.

24. Zhang M, Wang H, Liao M, Chen X, Graner, Zhu X, Zhang J, Yang Q, Lu H, Zhou B, Chen X*. Diagnosis of Latent Tuberculosis Infection in BCG-Vaccinated subjects in China by Interferon-γ Elispot Assay. Int J Tuberc Lung Dis. 2010; 14(12):1556-63.

25. Chen X, Zhang M, Liao M, Graner, Yang Q, Wu C, Liu H, Zhou B, Reduced Th17 Response in Patients with Tuberculosis Correlate with IL-6R Expression on CD4+ T Cells. Am J Respir Crit Care Med.  2010;181(7):734-42.

26. Chen X*, Zhang M, Zhu X, Deng Q, Liu H, Larmonior N, Jin Q, Zhou B，Engagement of Toll-like Receptor 2 on CD4 T cells Facilitates Local Immune Responses In Patients With Tuberculous Pleurisy, J Infect Dis. （IF 5.68）2009;200(3):399-408

27. Chen X*, Yang Q, Zhang M, Graner M, Zhu X, Larmonior N, Liao M, Yu W, Deng Q, Zhou B. Diagnosis of Active Tuberculosis in China Using an In-House Interferon gamma Enzyme-Linked Immunospot Assay. Clin Vaccine Immunol. 2009; 16(6):879-84.

28.  Chen X*, Zhou B, Li M, Deng Q, Wu X, Le X, Wu C, Larmonier N, Zhang W, Zhang H, Wang H, Katsanis, E. CD4+CD25+FoxP3+ regulatory T cells suppress Mycobacterium tuberculosis immunity in patients with active disease. Clinical Immunology, 2007; 123(1):50-59.

D. Research Support

Ongoing:

Thirteen-Fifth Mega-Scientific Project on prevention and treatment of AIDS, viral hepatitis and other infectious diseases

(Grant No. 2012ZX10003002-005)         01/01/2012-31/12/2015

“Screen and identification of immune biomarker for diagnosis of bacterium-negative tuberculosis”The major goal of this grant is to screen and identify biomarkers for diagnosis of tuberculosis.  

Role: Principal Investigator (project leader)

Direct RMB ￥3,050,000   (a total of RMB ￥36,130,000 for the whole project including 19 teams)

National Nature Science Foundation of China

(Grant No.81273140)          01/2018-12/2021

“Inhibition of IL-6R expression on CD4 T cells by Mycobacterium tuberculosis through DNA methylation”The major goal of this grant is to define the role of DNA methylation of IL6R on Mtb reduced IL6R expression on CD4 T cells.

Role: Principal Investigator

Direct CNY 560,000

The National Science Fund for Distinguished Young Scholars

 (NSFC Grant No.81525016)         01/2016-12/2020

“Infection and Immunity.”The major goal of this grant is to investigate the potential of xCT as a target for host directed therapy against TB.

Role: Principal Investigator

Direct RMB ￥4,000,000

Shenzhen Science and Technology

Grant （JSGG20160427104724699）         07/2016-12/2018

Host-directed therapy against tuberculosis in patients with diabetes.The major goal of this grant is to define and develop strategy for host directed therapy against TB in patients with diabetes.

Role: Principal Investigator

 Direct RMB ￥3,500,000

Completed:

National Nature Science Foundation of China

( Grant No.81273140)         01/2013-12/2016

“IL1B/TGFB/Il6/IL17A gene SNPs alter the susceptibility to tuberculosis through regulation of IL-17 expression”The major goal of this grant is to define the host genetics control of IL-17 response in tuberculosis and its contribution to susceptibility to human tuberculosis.

Role: Principal Investigator

Direct RMB ￥750,000

National Nature Science Foundation of China

(Grant No.81171535)         01/01/2012-31/12/2015

“Inhibtion of Th17 response by CD19+CD5+CD1d+ B cells: its mechanism and significane in human tuberculosis”The major goal of this grant is to determine the regulatory role and mechanism of Breg on Th17 response in human tuberculosis

Role: Principal Investigator

Direct RMB ￥580,000

Twelfth-Fifth Mega-Scientific Project on prevention and treatment of AIDS, viral hepatitis and other infectious diseases

(Grant No. 2012ZX10003002-005)         01/01/2012-31/12/2015

“Screen and identification of immune biomarker for diagnosis of active tuberculosis”The major goal of this grant is to screen and identify a group of cell surface biomarker for diagnosis of tuberculosis.

 Role: Principal Investigator

Direct RMB ￥1,940,000

Shenzhen Science and Technology

 Grant         01/01/2012-31/12/2014

“Shenzhen Key Laboratory of Infection and Immunity”The major goal of this grant is to set up facility and research team for research in infection and immunity.

Role: Principal Investigator

Direct RMB ￥5,000,000

National Nature Science Foundation of China

(30872258)         01/01/2007-31/12/2010

“Investigation of the role of Th17 in immunopathogenesis of human tuberculosis”

Role: Principal Investigator

Direct RMB ￥330,000

Eleven-Fifth Mega-Scientific Project on prevention and treatment of AIDS, viral hepatitis and other infectious diseases

(Grant No. 2008ZX10003002-005)         01/01/2008-31/12/2011

“Screen and identification of biomarker for diagnosis of tuberculosis”

Role: Principal Investigator

Direct RMB ￥2,000,000

Eleven-Fifth Mega-Scientific Project on prevention and treatment of AIDS, viral hepatitis and other infectious diseases

 (Grant No. 2008ZX10003-012)         01/01/2008-31/12/2011

“Investigation of immune response correlate with protection against human tuberculosis”

 Role: Principal Investigator

Direct RMB ￥2,560,000

National Nature Science Foundation of China

 (30671857)          01/01/2006-31/12/2009

“The role of regulatory T cells in tuberculosis”

Role: Principal Investigator

Direct RMB ￥290,000

Shenzhen Science and Technology

 Grant         01/01/2008-31/12/2009

“development of antigen-specific IFN-gamma Elispot kit for diagnosis of mycobacterium tuberculosis infection”

Role: Principal Investigator

Direct RMB ￥450,000