BIOGRAPHICAL SKETCH

NAME: Ren, Xinglin?????????????????????????Email: majrenxl@fmmu.edu.cn?????????????????tel: ??+86-0755-21839172

POSITION TITLE: Professor of Respiratory Medicine，Shenzhen?University?General Hospital

EDUCATION/TRAINING

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INSTITUTION AND LOCATION	DEGREE ?	? Completion Date MM/YYYY ?	FIELD OF STUDY
Suzhou Medical College, Suzhou, China	B. Med	06/1989	Clinical Medicine
The Fourth Military Medical University, China	M.Sc.	06/1996	Respiratory Medicine
The Third Military Medical University, China	Ph.D.	06/2006	Respiratory Medicine
University of California, Irvine,?California, USA	Visiting Scholar	10/2001 03/2002	Medical Department
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1. Personal Statement

I have long been engaged in the research of targeted gene therapy, early diagnosis, and pathogenesis of lung cancer. I focus on EGFR TKI resistance in lung cancer, explore effective intervention strategies and treatment methods, and have achieved certain results, which provided a powerful driving force for the development of lung cancer treatment. Under the guidance of Professor Qian Guisheng and Professor Yang Angang, I completed my Ph.D. thesis which is “Experimental study on the inhibition of growth of NSCLC by RNA interference of HER2”. ?In the past five years, I had undertaken two projects of the National Natural Science Foundation of China and participated in two other projects. I published eight SCI papers and one national core journals in the recent five years, including two first author papers and two correspondence author papers. One of the published SCI papers was reviewed and quoted by the magazine of Lung Cancer in early 2010. I was granted a national invention patent (China) and participated in the 2014 European Respiratory Association annual meeting where I also gave a speech. Currently, I am mentoring 2 Ph.D. candidates and 3 MSc candidates.

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2. Positions and Honors

Positions and Employment

08/19889–08/1993 Resident Physician, Department of Internal Medicine, Xi'an 141^th?Hospital, Xi'an, China

08/1996 – 08/1997 Resident Physician/?Teaching Assistant,?PCCM, Xi jing Hospital, Xi'an, China

08/1997 – 08/2009 Attending Physician/ Lecturer, PCCM, Xi jing Hospital, Xi'an, China

10/2001 – 03/2002 Visiting Scholar, University of California, Irvine, California, USA

09/2009 – 04/2018 Associate Senior Physician/Associate Professor, PCCM, Xi jing Hospital, Xi'an, China

04/2018?– present ?????Director/Professor, Respiratory Disease Department, Shenzhen?University?General Hospital, Shenzhen, China

Organizing International Meetings

Other Experience and Honors

1. National invention patent (China, ZL 201410081527), Fusion protein based on anti-EGFR single chain antibody and arginine nonamer and application.2016
2. Editorial board,?International journal of respiratory diseases, ?-
3. Standing Committee Member,?Shaanxi Provincial Individualized Diagnosis and Treatment Committee?
4. Standing Committee Member, Lung Cancer Group of the Shaanxi Respiratory Society?
5. standing committee member,?Respiratory Professional Committee of the Shaanxi Rehabilitation Medical Association
6. "a good teacher for Resident",?Chinese Medical Doctor Association, 2017
7. PCCM trainer, Chinese Medical Doctor Association, 2017
8. Medical ethics award, the forth military medical university, 2016
9. Standardized training base standardized training physician excellent teacher, the forth military medical university, 2015

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

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

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Overcome EGFR TKIs Resistan ce

Epidermal growth factor rector tyrosine kinase inhibitors (EGFR TKIs) have a significant curative effect on EGFR positive non-small cell lung cancer patients; however EFGR T790M mutation, MET gene amplification, and the double expression of EGFR/HER2 all lead to EGFR-TKI resistance in these patients. Although the irreversible second-generation EGFR TKIs combined with MET inhibitor has been used to overcome EGFR-TKI resistance, ?its advantage was minimal, while the side effect was intolerant. Previous studies of our team and others had indicated that EGFR-targeted multi-oncogene silencing strategy might overcome the EGFR-TKI resistance. In our last study, a siRNA therapy mediated by single chain fragment antibody (scFv) showed promising therapeutic effect both in vivo and in vitro. Generally, siRNA that can silence EGFR, KRAS, MET and HER2 had been designed, and then complexes of EGFR-scFv/scFv-9R-siRNA were constructed. The scFv-9R-siRNA effectively inhibited the expression of EGFR, KRAS, MET and HER2 in EGFR positive tumor cells. Through the specific recognition and internalization of the targeted cells, this complex showed a potent inhibitory effect on the expression of the three mutations of EGFR-TKI resistance cells.

1)Lu Y, Liu L, Wang Y, Li F, Zhang J, Ye M, Zhao H, Zhang X, Zhang M, Zhao J, Yan B, Yang A, Feng H, Zhang R, Ren X. siRNA delivered by EGFR-specific scFv sensitizes EGFR-TKI-resistant human lung cancer cells. Biomaterials. 2016; 76:196-207.

2)Lu Y, Wang Y, Zhang M, Liu L, Li F, Zhang J, Ye M, Zhao H, Zhao J, Yan B, Yang A, Zhang R, Li X, Ren X. HER2-siRNA delivered by EGFR-specific single chain antibody inhibits NSCLC cell proliferation and tumor growth. Oncotarget. 2016; 7(17):23594-607.

3)Lu Y, Li A, Lai XF, et al. Identification of differentially expressed genes and signaling pathways using bioinformatics in interstitial lung disease due to tyrosine kinase inhibitors targeting the epidermal growth factor receptor. Investigational New Drugs.2018:1-17.

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4. Research Support

Ongoing Research Support

NSFC(China) key project (8187880) 01/01/2019?to 12/31/2022

Xinlin Ren, PI ￥570,000 (direct cost)

The effect and mechanism of scFv-shikonin nanoparticles?in reversing the drug resistance of the EGFR-TKIs

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Completed Research Support

NSFC (China) key project (8117222) 01/01/2011?to 12/31/2015

Xinlin Ren, PI ￥630,000 (direct cost)

The study on gene intervention to overcome NSCLC EGFR-TKI resistance combined with EGFR multiple target

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NSFC (China ???????????????????????? 01/01/2009 to 12/31/2011

Xinlin Ren, Member ￥320,000

The study on effect of Septing4 protein on platelet a-granule membrane stability

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NSFC (China) (30170355) 01/01/2002 to 12/31/2004

Xinlin Ren, Member

Mechanism study on changes of arterial reactive differentiation induced by simulated weightlessness

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NSFC (China) (39800157) 01/01/1999 to 12/31/2001

Xinlin Ren, Member

Experimental study on changes of cerebral arteries under simulated weightlessness and its mechanism

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Military Key Laboratory Fund Project ?????09/01/1997 to 09/30/1998

Xinlin Ren, PI ??????????????????????????????????????????

Expression of epidermal growth factor receptor in lung cancer and its application in in vivo imaging

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Shaanxi Social Development Science and Technology Research Fund Project (S2011sf1381)

Xinlin Ren, PI ?????????????????????????????????????????????????????01/01/2012?to 12/31/2013

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Screening of sensitivity markers of EGFR TKIs in Chinese NSCLC patients

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AstraZeneca Collaborative Fund Project 01/01/2009?to 12/31/2013

Xinlin Ren, PI ?????

Predictive biomarkers for EGFR therapy in patients with advanced non-small cell lung cancer

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

1.? Lu Y, Liu L, Wang Y, Li F, Zhang J, Ye M, Zhao H, Zhang X, Zhang M, Zhao J, Yan B, Yang A, Feng H, Zhang R, Ren X * . ?siRNA delivered by EGFR-specific scFv sensitizes EGFR-TKI-resistant human lung cancer cells. Biomaterials. 2016; 76:196-207. 　 　

2.? Lu Y, Wang Y, Zhang M, Liu L, Li F, Zhang J, Ye M, Zhao H, Zhao J, Yan B, Yang A, Zhang R, Li X, Ren X * . HER2-siRNA delivered by EGFR-specific single chain antibody inhibits NSCLC cell proliferation and tumor growth. Oncotarget. 2016; 7(17):23594-607. 　 　

3.? Lu Y, Li A, Lai XF, ?Ren X * ?et al. Identification of differentially expressed genes and signaling pathways using bioinformatics in interstitial lung disease due to tyrosine kinase inhibitors targeting the epidermal growth factor receptor. Investigational New Drugs . 2018:1-17 　 　

4.? Zhang R, Bai YG, Lin LJ, Bao JX, Zhang YY, Tang H, Cheng JH, Jia GL, ?Ren X * , Ma J. Blockade of AT1 receptor partially restores vasoreactivity, NOS expression, and superoxide levels in cerebral and carotid arteries of hindlimb unweighting rats. J Appl Physi ol. 2009 ;106(1):251-8. 　 　

5.? ? Ren X * , Xu YM, Bao W, Fu HJ, Wu CG, Zhao Y, Li ZK, Zhang J, Li SQ, Chen WQ, Wang T, Zhang R, Zhang LH, Qian GS, Chen SY, Jia LT, Yang AG.Inhibition of non-small cell lung cancer cell proliferation and tumor growth by vector-based small interfering RNAs tar geting HER2/neu. Cancer Letts. 2009;281(2):134-43. 　 　

6.? Ren X * , Zhang R, Zhang YY, Liu H, Yu JW, Cai Y, Wang ZC, Purdy RE, Ma J. Nitric oxide synthase activity in the abdominal aorta of rats is decreased after 4 weeks of simulated microgravity. Clin Exp Pharmacol Physiol. 2011;38(10):683-7. 　 　

7.? Y.K. Shi, L. Wang, B.H. Han, W. Li, P. Yu, Y.P. Liu, C.M. Ding, X. Song, Z.Y. Ma, X.L.Ren , J.F. Feng, H.L. Zhang, G.Y. Chen, X.H. Han, N. Wu, C. Yao, Y. Song, S.C. Zhan,W. Song, X.Q. Liu, S.J. Zhao, Y.C. Lin, X.Q. Ye, K. Li, Y.Q. Shu, L.M. Ding, F.L.Tan, Y . Sun. First-line icotinib versus cisplatine/pemetrexed plus pemetrexed maintenance therapy in lung adenocarcinoma patients with sensitizing EGFR mutation (CONVINCE). ? J Clin Oncol 34, 2016 (suppl; abstr 9041). 　 　

8.? Ye M, Zhang X, Li N, Zhang Y, Jing P, Chang N, Wu J, Ren X , Zhang J. ALK and ROS1 as targeted therapy paradigms and clinical implications to overcome crizotinib resistance.Oncotarget. Oncotarget. 2016 Mar 15;7(11):12289-304. doi: 10.18632/oncotarget.6935. Review. 　 　

9.? Zhang J, Cui LB, Tang X, Ren XL, ?Shi JR, Yang HN, Zhang Y, Li ZK, Wu CG, Jian W, Zhao F, Ti XY, Yin H. DW MRI at 3.0 T versus FDG PET/CT for detection of malignant pulmonary tumors. Int J Cancer. 2014 Feb 1;134(3):606-11. 　 　

10.? Zhikui L, Changcun G, Yongzhan N, Fengtian H, Xingling R , Shujun L, Zheyi H, Ying H, Xin W, Daiming F. Screening and identification of recombinant anti-idiotype antibodies against gastric cancer and colon cancer monoclonal antibodies by a phage-displayed single-chain variable fragment library. J Biomol Screen. 2010 Mar;15(3):308-13. 　 　

11.? Zhang J, Zhao YL, Ye MX, Sun G, Wu H, Wu CG, Ren XL , Jian W. Rapidly progressive diffuse cystic lesions as a radiological hallmark of lung adenocarcinoma. J Thorac Oncol. 2012 Feb;7(2):457-8. 　 　

12.? Bao W, Fu HJ, Xie QS, Wang L, Zhang R, Guo ZY, Zhao J, Meng YL, Ren XL , Wang T, Li Q, Jin BQ, Yao LB, Wang RA, Fan DM, Chen SY, Jia LT, Yang AG. HER2 interacts with CD44 to up-regulate CXCR4 via epigenetic silencing of microRNA-139 in gastric cancer cells. Gastroenterology. 2011 Dec;141(6):2076-2087. 　 　

13.? Zhang J, Zhang T, Ti X, Shi J, Wu C, Ren X , Yin H. Curcumin promotes apoptosis in A549/DDP multidrug-resistant human lung adenocarcinoma cells through an miRNA signaling pathway. Biochem Biophys Res Commun. 2010 Aug 13;399(1):1-6. 　 　

14.? Zhang J, Du Y, Wu C, ?Ren X , Ti X, Shi J, Zhao F, Yin H. Curcumin promotes apoptosis in human lung adenocarcinoma cells through miR-186* signaling pathway.Oncol Rep. 2010 Nov;24(5):1217-23.