Research Interest: Stem Cell Biology; Breast Cancer Dormancy; Neural Regulation of Hematopoiesis, the Immunology and Clinical Application of Adult Human Mesenchymal Stem Cells. 

EDUCATION

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

Research Interest:

  CRISPR technology

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.

PUBLICATIONS

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.

Research Interest: Focuses on Aging-Related Diseases and Stem Cell Transplantation. 

Research Interest: Neurological Disability.

Research Interest: Neuropsychopharmacology of Lipid Transmitters (CTS643, Andalusian Ministry of Economy, Innovation, Science and Employment): The Group is Formed in the University Regional Hospital of Malaga, in Collaboration with the University of Malaga, and Integrated Into the Biomedical Research Institute of Malaga (IBIMA). Our Interest Focuses on the Role that Regulatory Lipid Molecules, Mainly Lysophosphatidic Acid, Exerted on the Central Nervous System and Related Mainly to the Neural Genesis (Neurogenesis / Gliogenesis) and its Effect on Behavioral Level. It Also Examines the Role of Lysophosphatidic Acid in the Dynamic Processes that Regulate Neuroinflammation and Demyelination in Multiple Sclerosis, Studying Animal Models and Samples from Patients with Multiple Sclerosis, As Well As Mesenchymal Cell Therapy for the Disease.

Research Interest: Genes Involved in Cell Cycle Regulation, Differentiation, Apoptosis and Senescence Such as the Retinoblastoma (RB) Family. He has Evaluated the Role of Retinoblastoma Genes in the Regulation of Cell Proliferation, Differentiation and Apoptosis in
Cancer and Normal Stem Cells. In Detail, his Group has Analyzed the Biology of Neural Stem Cells and Mesenchymal Stem Cells. These Studies Prompted the Attention Also on Chromatin
Remodeling Factors that Interact with RB Family Members and Play a Key Role in the Life of StemCells.

Research Interest:

Two Major Projects are Currently Underway in the Laboratory.
A Cell Reprogramming Technique Has Been Used to Convert Heterogeneous Malignant Breast Cancer Cells into Induced Pluripotent Stem Cells Using Sox2/Oct4/Nanog Proteins. Dr. Wu’s Laboratory is Clarifying these Induced Pluripotent Stem Cells for their Differentiation Potential and Oncogenic Properties, and Try to Develop a Novel Cell Converting Therapy for Malignant Breast Cancer Treatment.
Metastasis, the Spread of Cancer Cells from the Primary Tumor To Distant Organs, Is The Most Dreadful Development Of Breast Cancer, As Well As Other Neoplastic Diseases. Although Metastasis Contributes To Over 90% Of Human Cancer Mortality, The Molecular Mechanism Of This Process Remains Largely Unknown. Dr. Wu’s Laboratory Is In The Process Of Identifying Molecular Signatures Involved In Breast Cancer Metastasis Using Integrative Genetic, Epigenetic And Proteomic Approach, As Well As Animal Models And Clinical Specimens. 

Research Interest: Drug Discovery and Development.

Dr. Monther AlAlwan is a scientist at the Stem Cell and Tissue Re-engineering Program (SCTRP), King Faisal Specialist Hospital and Research Centre, as well as an Associate professor at Alfaisal University, Riyadh Saudi Arabia. He holds M.Sc. and Ph.D. in Immunology from Dalhousie University (Halifax, Canada). Dr. AlAlwan conducted a 3-years postdoctoral fellowship studying signaling in immune cells at the University of Manitoba, Canada. During his graduate studies and postdoctoral fellowship, Dr. AlAlwan made substantial contribution in the immunology field, particularly his groundbreaking discovery that highlighted the significance of the dendritic cells in the immunological synapse. After joining the SCTRP in 2007, he shifted gear to study cancer, where he identified novel mechanisms that regulate cancer metastasis and chemoresistance. Currently, he is actively involved in dissecting the molecular pathways that regulate the function of cancer stem cells and how this related to chemoresistance and metastasis. Dr. AlAlwan is an author in 20 peer-reviewed publications, has delivered several invited lectures and is a regular reviewer for various international journals.   

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)

URL: https://www.wjgnet.com/2218-6204/MemberDetail/42530

publications:

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.

Research Interest: Actually Works as Young Researcher in Projects Regarding Genomics, Proteomics and Inflammatory Aspects of Human Breast Cancer and Chronic Diseases. 

Ricardo Alaxandre de Azevedo, PhD, Graduated in Biological Science by the University ‘Santa Cecília’- Santos (Brazil) in 2002, MSc degree in Biotechology by the University of São Paulo (Brazil) in 2010, and Ph.D. in Toxinology by the Butantan Institute (Brazil) in 2014. Presently, Postdoctoral Fellow, Department Immunology, Laboratory of Tumor Immunology, University São Paulo, July 2014-current. Also occupy position of  Research Scientist, and Coordinator of Biological Assays Division at ALCHEMY, RESEARCH AND DEVELOPMENT, February-current.  I have experience and scientific production in the area of Apoptosis and cell cycle signaling, peptides and peptidases, molecular biology and cancer genetics, cells immunology, with emphasis on biochemotherapy and immunotherapy of cancer, focusing murine melanoma and human tumors. 

Research Interest: Cancer Metabolism, Metabolomics, NMR and MRI Methods, Systems Biology.

Research Interest: Cancer Stem Cell, Anticancer Agent, Metastasis, Cell Survival, Cell Migration, Apoptosis, Molecular and Cell Signaling, Transcription Factors, Xenograft Model, Stem Cell Based Therapy.

Research Interest: Hematopoietic Stem Cell Transplanting, Cell Therapy and Everything in the Field of Publication and Education.