2006 – 2009
M.S. in Microbiological and Biochemical Pharmacy
Shanghai Jiaotong University, Shanghai, China
2001 - 2005
B.S. in Biotechnology (Fermentation Engineering)
Shanghai Normal University, Shanghai, China
Stem Cell Research and Therapy
Gynecological Disease Research
Autoimmune Disease Research
RESEARCH INTERESTS AND SKILLS
My scientific interests are to understand how genetic and molecular programs can yield the complex biological behaviors. As a medical research scientist, synthetic biologist and bioengineer, I am passionate about the applications of diverse biotechnological tools to understand genomics and explore the mechanism of genomic control as well as incidence of diseases, which allow comprehensive understanding, manipulating, and engineering of sophisticated biological systems. I aim to understand cellular or organismal behaviors in both space and time thus benefit the biomedical research, translational studies and cell therapy.
I am skilled in cell culture (primary/linage) and cellularity detections (CCK8, FACS etc); molecular cloning and detection (plasmid construction, RT-PCR, western blot etc); protein [removed]prokaryotic expression system) and purification (ionexchange and affinity chromatography); immunohistochemistry and immunocytochemistry detection; and animal model construction.
Research Grant Details:
National Natural Science Foundation of China (Grant No. 81502233)
Existing evidence indicates that PPI (protein-protein interaction) contributes to the tumorigenesis of endometrial carcinoma, but the mechanisms involved in it remain largely unknown. In our previous study, we found that ATF3 participating in the development of various different kinds of cancer, expressed higher in the epithelium of normal endometrial tissue than that detected in pathnological tissue, and interacted with JunB which expressing higher in the epithelium of endometrial cancer tissue than that detected in normal endometrial tissue, via yeast-two-hybrid assay. Additionally, over-expression of ATF3 led to the inhibition of cell proliferation, migration and invasion, with the down-regulation of JunB and inflammatory factor. Therefore, we put forward a hypothesis that ATF3 might inhibit the expression of inflammatory genes and the development of endometrial cancer by binding with JunB andmitigating with it. This study was designed to utilize the mRNA expression microarray analysis, CRISPR/Cas9 and orthotopic endometrial carcinoma model in nude mice combined with molecular biological techniques to explore the cell signal transductions of ATF3 and JunB in EC, demonstrate the mechanism of development of EC, and provide new therapeutic targets for it, which contributes greatly to the patients suffering from endometrial cancer.
1． Wang Fangyuan(#), Qi Stanley Lei(*). Applications of CRISPR Genome Engineering in Cell Biology. Trends in Cell Biology. 2016 Nov;26(11):875-888.
2． Wang Fangyuan(#), Zhao Dehua, Qi Lei Stanley(*). Application of genome engineering in medical synthetic biology. Sheng Wu Gong Cheng Xue Bao. 2017 Mar 25;33(3):422-435.
3． Wang Fangyuan(#), Gao Jin, Malisani Alyssa, Xi Xiaowei, Han Wei, Wan Xiaoping (*), Mouse Resistin (mRetn): cloning, expression and purification in Escherichia coli and the potential regulative effects on murine bone marrow hematopoiesis. BMC Biotechnol, 2015 Nov 16;15(1):105.
4． Wang Fangyuan(#), Wang Li, Yao Xiaofen, Lai Dongmei(*). Human amniotic epithelial cells can differentiate to granulosa cells and restore folliculogenesis in a mouse model of chemotherapy-induced premature ovarian failure. Stem Cell Res Ther. 2013 Oct 14;4(5):124-134.
5． Liu Yanxia(#), Yu Chen(#), Daley Timothy Patrick(#), Wang Fangyuan, Cao William S., Bhate Salil, Lin Xueqiu, Still II Chris, Liu Honglei, Zhao Dehua, Wang Haifeng, Xie Xinmin S., Ding Sheng, Wong Wing Hung, Wernig Marius, Qi Lei Stanley. CRISPR Activation Screens Systematically Identify Factors that Drive Neuronal Fate and Reprogramming. Cell Stem Cell. 2018 Nov 1;23(5):758-771.
6． Yan Qin(#), Wang Fangyuan, Miao Yi, Wu Xiaomei, Bai Mingzhu, Xi Xiaowei, Feng Youji(*). Sex-determining region Y-box3 (SOX3) functions as an oncogene in promoting epithelial ovarian cancer by targeting Src kinase. Tumour Biol. 2016 Sep;37(9):12263-12271.
7． Lai Dongmei(#)(*), Wang Fangyuan, Yao Xiaofen, Zhang Qiuwan, Wu Xiaoxing, Xiang Charlie(*). Human endometrial mesenchymal stem cells restore ovarian function through improving the renewal of germline stem cells in a mouse model of premature ovarian failure. J Transl Med. 2015 May 12;13:155.
8． Lai Dongmei(#)(*), Wang Fangyuan, Dong Zhangli, Zhang Qiuwan. Skin-derived mesenchymal stem cells help restore function to ovaries in a premature ovarian failure mouse model. PLoS One. 2014 May 30;9(5):e98749.
9． Lai Dongmei(#)(*), Wang Fangyuan, Chen Yifei, Wang Li, Wang Yanlin, Cheng Weiwei. Human amniotic fluid stem cells have a potential to recover ovarian function in mice with chemotherapy-induced sterility. BMC Dev Biol. 2013 Sep 4;13(1):34.
10． Lai Dongmei(#)(*), Wang Fangyuan, Chen Yifei, Wang Chunhui, Liu Sha, Lu Bufeng, Ge Xuerui, Guo Lihe. Human ovarian cancer stem-like cells can be efficiently killed by γδ T lymphocytes. Cancer Immunol Immunother. 2012 Jul;61(7):979-89.
11． Che Qi(#), Liu Binya, Wang Fangyuan, He Yinyan, Lu Wen, Liao Yun, Gu Wei, Wan Xiaoping(*). Interleukin 6 promotes endometrial cancer growth through an autocrine feedback loop involving ERK-NF-kappaB signaling pathway. Biochem Biophys Res Commun, 2014, 446(1):167-172.
12． Lai Dongmei(#)(*), Ma Li, Wang Fangyuan. Fibroblast activation protein regulates tumor-associated fibroblasts and epithelial ovarian cancer cells. Int J Oncol. 2012 Aug;41(2):541-50.
13． Lai Dongmei(#)(*), Chen Yifei, Wang Fangyuan, Jiang Lizhen, Wei Chunsheng. LKB1 Controls the Pluripotent State of Human Embryonic Stem Cells. Cellular Reprogramming. April 2012, 14(2): 164-170.
14． Chen Zheng(#), Che Qi, He Xiaoying, Wang Fangyuan, Wang Huihui, Zhu Minjiao, Sun Jing(*), Wan Xiaoping(*). Stem cell protein Piwil1 endowed endometrial cancer cells with stem-like properties via inducing epithelial-mesenchymal transition. BMC Cancer, 2015 Oct 27;15:811.
15． Chen Zheng(#), Che Qi, Jiang Feizhou, Wang Huihui, Wang Fangyuan, Liao Yun, Wan Xiaoping(*). Piwil1 causes epigenetic alteration of PTEN gene via upregulation of DNA methyltransferase in type I endometrial cancer. Biochem Biophys Res Commun, 2015 Aug 7;463(4):876-80.
16． Liao Yun(#), He Xiaoying, Qiu Haifeng, Che Qi, Wang Fangyuan, Lu Wen, Chen Zheng, Qiu Meiting, Wang Jingyun, Wang Huihui, Wan Xiaoping(*). Suppression of the epithelial-mesenchymal transition by SHARP1 is linked to the NOTCH1 signaling pathway in metastasis of endometrial cancer. BMC Cancer. 2014, 14：487。
17． Huang Haili(#), Wang Yajing, Zhang Qingyu, Liu Bin, Wang Fangyuan, Li Jingjing, Zhu Runzhi(*). Hepatoprotective effects of baicalein against CCl4-induced acute liver injury in mice. World J Gastroenterol 2012 Dec 7;18(45):6605-6613.
18． Wang Huihui(#), Bao Wei, Jiang Feizhou, Che Qi, Chen Zheng, Wang Fangyuan, Tong Huan, Dai Chenyun, He Xiaoying, Liao Yun, Liu Binya, Sun Jing, Wan Xiaoping(*). Mutant p53 (p53-R248Q) functions as an oncogene in promoting endometrial cancer by up-regulating REGgamma. Cancer Lett. 2015 May 1;360(2):269-79.
19． Xia Peng(#), Gao Jin, Guan Wen, Li Jingjing, Yu Xiaolan, Wang Fangyuan, He Honglin, Deng Qing, Zhou Liang, Yuan Yunsheng, Han Wei(*), Yu Yan(*). Production of bioactive recombinant rat soluble receptor for advanced glycation end products (rrsRAGE) in Pichia pastoris. Protein Expr Purif, 2017 Oct;138:81-87.
20． Zhu Minjiao(#), Che Qi, Liao Yun, Wang Huihui, Wang Jingyun, Chen Zheng, Wang Fangyuan, Dai Chenyun, Wan Xiaoping(*). Oncostatin M activates STAT3 to promote endometrial cancer invasion and angiogenesis. Oncol Rep. 2015 Jul;34(1):129-38.
21． Che Qi(#), Liu Binya, Liao Yun, Zhang Huijuan, Yang Tingting, He Yinyan, Xia Yuhong, Lu Wen, He Xiaoying, Chen Zheng, Wang Fangyuan, Wan Xiaoping(*). Activation of a positive feedback loop involving IL-6 and aromatase promotes intratumoral 17beta-estradiol biosynthesis in endometrial carcinoma microenvironment. Int J Cancer. 2014 Jul 15;135(2):282-94.
22． Liu Yuan(#), Murray-Stewart T, Casero RA Jr, Kagiampakis I, Jin L, Zhang J, Wang H, Che Qi, Tong Huan, Ke Jieqi, Jiang Feizhou, Wang Fangyuan, Wan Xiaoping(*). Targeting hexokinase 2 inhibition promotes radiosensitization in HPV16 E7-induced cervical cancer and suppresses tumor growth. Int J Oncol. 2017 Jun;50(6):2011-2023.
23． Ke Jieqi(#), Yang Yixia(#), Che Qi, Jiang Feizhou, Wang Huihui, Chen Zheng, Zhu Minjiao, Tong Huan, Zhang Huilin, Yan Xiaofang, Wang X, Wang Fangyuan, Liu Yuan, Dai Chenyun, Wan Xiaoping(*). Prostaglandin E2 (PGE2) promotes proliferation and invasion by enhancing SUMO-1 activity via EP4 receptor in endometrial cancer. Tumour Biol. 2016 Sep;37(9):12203-12211.
24． Jiang Feizhou(#), He Yinyan, Wang Huihui, Zhang Huilin, Zhang Jian, Yan Xiaofang, Wang Xiaojun, Che Qi, Ke Jieqi, Chen Zheng, Tong Huan, Zhang Yongli, Wang Fangyuan, Li Yiran, Wan Xiaoping(*). Mutant p53 induces EZH2 expression and promotes epithelial-mesenchymal transition by disrupting p68-Drosha complex assembly and attenuating miR-26a processing. Oncotarget, 2015 Dec 29;6(42):44660-74.
(#) First Author, (*) Correspondence Author.
Dr. Edgar Grinstein is a Principal Investigator at the Heinrich Heine University in Düsseldorf (Germany). He researches hematopoietic stem cells and progenitor cells, signal transduction, gene transcription regulation. He has more than 11 years of experience as Editor-In-Chief at SAGE Publications Inc. (USA) and Libertas Academica (New Zealand), and also serves as Deputy Editor-In-Chief for Baishideng Publishing Group (USA).
Raised in a family of researchers – both parents are PhD scientists - he received his PhD summa cum laude in Molecular Biology from the Humboldt University and the Max-Delbrück Center for Molecular Medicine in Berlin. He has published a number of papers in high-ranking journals and received a highly regarded Research Award from Dr.-Günther- and Imme-Wille-Foundation. Dr. Grinstein qualified as Professor in Molecular Medicine at the University of Düsseldorf in 2008 and is a Visiting Professor at the University of Latvia (Latvia, European Union) since 2010.
Dr. Grinstein`s research in the field of hematopoietic stem and progenitor cells, funded by research grants from German Research Foundation (DFG) and José Carreras Leukämie-Stiftung (José Carreras Foundation), has focused on markers, signal transduction and transcriptional control. Among other important findings made, his research group provided new insights into the role of the prominent surface marker AC133/CD133 (Leukemia 2015; 29: 2208-2220), that is expressed on stem/progenitor cells in normal hematopoiesis as well as on tumor-initiating cells in certain hematological malignancies. The study analyzed the control of AC133/CD133 expression in hematopoietic stem/progenitor cells, and revealed the impact thereof on molecular network relevant to these cells.
Research Interest: hematopoietic stem cells and progenitor cells, cancer stem cells, stem cell markers, signal transduction, cell cycle control, regulation of apoptosis, gene transcription regulation
Grants: Principal Investigator of stem cell-related projects funded by German Research Foundation (DFG) and by José Carreras Leukämie-Stiftung (José Carreras Foundation)
Grinstein, E., and H.-D. Royer. 1995. Multiple octamer-binding proteins are targets for the cell cycle regulated nuclear inhibitor I-92. DNA Cell Biol. 14: 493-500.
Grinstein, E., I. Weinert, B. Droese, M. Pagano, and H.-D. Royer. 1996. Cell cycle regulation of nuclear factor p92 DNA-binding activity by novel phase-specific inhibitors. J. Biol. Chem. 271: 9215-9222.
Bargou, R.C., C. Wagener, K. Bommert, W. Arnold, P.T. Daniel, M.Y. Mapara, E. Grinstein, H.-D. Royer, and B. Dörken. 1996. Blocking of transcription factor E2F/DP by dominant-negative mutants in a normal breast epithelial cell line efficiently inhibits apoptosis and induces tumor growth in SCID mice. J. Exp. Med. 183: 1205-1213.
Bargou, R.C., F. Emmerich, D. Krappmann, K. Bommert, M.Y. Mapara, W. Arnold, H.-D. Royer, E. Grinstein, A. Greiner, C. Scheidereit, and B. Dörken. 1997. Constitutive nuclear factor kappaB-RelA activation is required for proliferation and survival of Hodkin’s desease tumor cells. J. Clin. Invest. 12: 2961-2969.
Janke, J., K. Schlüter, B. Jandrig, M. Theile, K. Kölble, W. Arnold, E. Grinstein, A. Schwartz, L.E. Schwarz, P.M. Schlag, B.M. Jockusch, and S. Scherneck. 2000. Suppression of tumoriginecity in breast cancer cells by the microfilament protein profilin1. J. Exp. Med. 191: 1675-1685.
Grinstein, E.,* F. Jundt, I. Weinert, P. Wernet, and H.-D. Royer. 2002. Sp1 as G1 cell cycle phase specific transcription factor in epithelial cells. Oncogene. 21: 1485-1492.
Grinstein, E., P. Wernet, P.J. Snijders, F. Rösl, I. Weinert, W. Jia, R. Kraft, Ch. Schewe, M. Schwabe, S. Hauptmann, M. Dietel, Ch. Meijer, and H.-D. Royer. 2002. Nucleolin as activator of human papillomavirus type 18 oncogene transcription in cervical cancer. J. Exp. Med. 196: 1067-1078.
Grinstein, E.,* Y. Shan, L. Karawajew, P.J. Snijders, C.J. Meijer, H.-D. Royer, and P. Wernet. 2006. Cell cycle controlled interaction of nucleolin with the retinoblastoma protein and cancerous cell transformation. J. Biol. Chem. 281: 22223-22235.
Grinstein, E.,* Y. Du, S. Santourlidis, J. Christ, M. Uhrberg, and P. Wernet. 2007. Nucleolin regulates gene expression in CD34 positive hematopoietic cells. J. Biol. Chem. 282: 12439-12449.
Grinstein, E.,* and P. Wernet. 2007. Cellular signaling in normal and cancerous stem cells. Cell. Signal. 19: 2428-2433.
This was the most read article of the Journal Cell. Signal. from July 2007 till March 2008. Source: SCIENCEDIRECT TOP 25 HOTTEST ARTICLES
Wethkamp, N., H. Hanenberg, C. Suschek, W. Wetzel, S. Heikaus, E. Grinstein, U. Ramp, R. Engers, H. Gabbert, and C. Mahotka. 2011. DAXX-beta and DAXX-gamma: two novel splice variants of the transcriptional co-repressor DAXX. J. Biol. Chem. 19576-19588.
Grinstein, E.,* C. Mahotka, and A. Borkhardt. 2011. Rb and nucleolin antagonize in controlling human CD34 gene expression. Cell. Signal. 23: 1358-1365.
Bhatia, S., S. Reister, C. Mahotka, R. Meisel, A. Borkhardt, and E. Grinstein.* 2015. Control of AC133 / CD133 and impact on human hematopoietic progenitor cells through nucleolin. Leukemia. 29: 2208-2220.
Mahotka, C., S. Bhatia, J. Kollet, and E. Grinstein.* 2018. Nucleolin promotes execution of the hematopoietic stem cell gene expression program. Leukemia. 32: 1865–1868.
Reister, S., C. Mahotka, N. van den Höfel, and E. Grinstein.* 2019. Nucleolin promotes Wnt signaling in human hematopoietic stem/progenitor cells. Leukemia. 33: 1052-1054.