Research Interest: Cell Reprogramming and Induced Pluripotent Stem Cells, Stem Cells and Neural Tissue Engineering, Mammalian Inner Ear Development and Hair Cell Regeneration.

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. 

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: Leptin Receptors (Lepr) are Expressed by Various Types of Stem Cells Including Mesenchymal Stem Cells, Hematopoietic Stem Cells, Embryonic Stem Cells and Induced Pluripotent Stem Cells. Leptin/Lepr Signaling is also a Central Regulator of Metabolism.

Research Interest: Tumor Immunology and Immunotherapy, Cancer Stem Cell Biology and Immunology, Obstetrics and Gynecology.

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: Neurology

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

Research Interest: Primarily in the Area of Behavioral Neuroscience.

Research Interest: Harnessed the Biological Principle that Pregnancy and Hormones Mimicking Pregnancy Induced Breast Cancer Prevention.  The Preventive Effect of Pregnancy is Mediated by the Induction of Differentiation of the Mammary Gland.  In Studies Performed in Humans, He has Found that During the Post-Menopausal Years the Breast of Both Parous and Nulliparous Women Contains Preponderantly Lob 1 that Differs Biologically By Exhibiting Different Susceptibility to Carcinogenesis, And Remodeling Of Chromatin That Emerges As Novel Marker For Defining The Concept Of Differentiation In The Adult Breast.  His Laboratory Has Studied The Genomic Profile Of Nulliparous And Parous Women In The Premenopausal And Postmenopausal Period And Find That There Are Genes Only Activated During The First Five Years After Pregnancy That May Contribute To The Increased Risk Experimented By Certain Women After Pregnancy And At The Same Time They Have Confirmed That Pregnancy Induces A Long Lasting Genomic Signature That Start After Pregnancy That Explain Its Preventive Effect. The Molecular Mechanism Related To Prevention Is Around The Chromatin Remodeling Process. Using The In Vitro In Vivo Model Developed In His Laboratory He Is Identifying Drugs That Can Control Chromatin Remodeling As A Preventive Strategy.

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

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

Research Interest: Effects of Chinese Herbal Medicine on Osteogenesis and Adipogenesis of Mesenchymal Stem Cells, Inhibitory Effects of Chinese Herbal Medicine on RANKL-Induced Osteoclastgenesis of RAW264.7 Cells, Effect of Chinese Herbal Medicine on Different Osteoporotic Rat Models, Establishment of the Screening Platform for Neuro-Regenerative Chinese Herbal Medicine by Using Rat Mesenchymal Stem Cells, Topical Application of Chinese Medicine in Musculoskeletal Injuries, Wound Healing, Cancer Stem Cells, Neuroprotection.

Research Interest: Stem Cells, Cancer, Immune Therapy, Regenerative Medicine.

Research Interest: Cell Biology, Genetics, Cancer Research, Cancer Biology, Cell Culture, PCR, Gene Regulation, Signaling Pathways