游正博 John Yu, M.D., Ph.D.
Office Address:
Institute of Stem Cell and Translational Cancer Research, Research building 6F, Chang Gung Memorial Hospital at Linkou, No.15, Wenhua 1st St., Kuei Shang, Taoyuan 333, Taiwan
Tel: (886-3)328-1200 ext. 7803 Fax: (886-3)328-1200 ext. 5214
E-mail: johnyu@cgmh.org.tw
123 Current Status:
  • Director, Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou
  • Director, Cell Therapy Center, Chang Gung Memorial Hospital at Linkou
  • Distinguished Chair Professor, Chang Gung Memorial Hospital and Chang Gung University
  • Distinguished Visiting Fellow, Institute of Cellular & Organismic Biology, Academia Sinica

Education:
  • M.D., National Taiwan University
  • Ph.D. in Biophysics, University of Chicago
  • Fellow in Biology, The Biological Laboratories, Harvard University

Focus of Interest:
  • Stem cell biology
  • Regulation of hematopoiesis
  • Tumorigenesis cell

Employment Records:
  • 2002–2005 Distinguished Research Fellow & Director, Institute of Zoology, Academia Sinica.
  • 2002–2013 Chief, Stem Cell Program, and Distinguished Research Fellow, The Genomics Research Center, Academia Sinica.
  • 2005–2009   President, Taiwan Society for Stem Cell Research
  • 2005–2009  Distinguished Research Fellow & Director, Institute of Cellular & Organismic Biology, Academia Sinica
  • 2009–2013 Distinguished Research Fellow, Institute of Cellular & Organismic Biology, Academia Sinica
  • 2013– Present Distinguished Visiting Fellow, Institute of Cellular & Organismic Biology, Academia Sinica

Professional Records:
  • 2013 – Present, Distinguished Chair Professor and Director, Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital and Chang Gung University
  • 2016 – Present, Director, Cell Therapy Center, Chang Gung Memorial Hospital
  • 2013– Present, Distinguished Visiting Fellow, Institute of Cellular & Organismic Biology, Academia Sinica
  • 2016 – 2018, “Consultant board of Center for Cell Therapy and Regenerative Medicine” at Taipei Medical University
  • 2009–2013, Distinguished Research Fellow, Institute of Cellular & Organismic Biology, Academia Sinica
  • 2005–2009, Director, Institute of Cellular & Organismic Biology, Academia Sinica
  • 2005–2009, President, Taiwan Society for Stem Cell Research
  • 2004–2013, Distinguished Research Fellow (Joint appointment), The Genomics Research Center, Academia Sinica
  • 2003–Present, Adjunct Professor, Graduate Institute of Clinical Medicine, College of Medicine National Taiwan University
  • 2002–2013, Chief, Stem Cell Program, and Distinguished Research Fellow, The Genomics Research Center, Academia Sinica.
  • 2002–2005, Distinguished Research Fellow & Director, Institute of Zoology, AcademiaSinica.
  • 1998 – 2002, Director, Experimental Hematology, Department of Molecular & Experimental Medicine, The Scripps Research Institute
  • 1990 – 1997, Associate Member, Department of Molecular & Experimental Medicine, The Scripps Research Institute
  • 1983 – 1989, Assistant Member, Department of Molecular Biology and Department of Molecular & Experimental Medicine, Research Institute of Scripps Clinic
  • 1977 – 1982, Assistant Member II, Department of Cellular & Developmental Immunology and Department of Immunology, Research Institute of Scripps Clinic

Honor and Awards:
  • Advisor Committee, Department of Stem Cell Biology, Kumamoto University, Japan, 2010-2012
  • Honorary President, Taiwan Society for Stem Cell Research, Taiwan, 2010-present
  • Senior editorial Board, American Journal of Stem Cells, 2012-present; Editorial Board, ISRN Hematology, 2010-present; Editorial board, International Journal of Hematology, 2009-present; International Advisory Board, Journal of Experimental and Clinical Medicine, 2012-present
  • The Steering Committee of Stem Cell Network in Asia-Pacific regions, 2007-present
  • Government Affairs Committee, International Society for Stem Cell Research, 2005-2010
  • International hESC Guidelines Task Force, Intl Society for Stem Cell Research, 2006-2007
  • 柳川研究講座, China Medical University, 2006; 台大內科經典講座, National Taiwan University Hospital, 2005; 姆山研究講座, Taipei Medical University, 2005
  • Adjunct Professorship, Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, 2004-present; National Taiwan Ocean University; 2004-present, National Defense Medical Center, 2004-present
  • Established Investigatorship Award, American Heart Association, 1978-1983
  • National Institutes of Health Individual Postdoctoral Fellowship, 1974-1977

Key Government Services:
  • Member, 衛生福利部醫事審議委員會技術小組, 2016-present
  • Deputy Chairman, 衛生福利部再生醫學及細胞治療發展諮議會, 2015-present
  • Member, 科技部再生醫學研究諮議委員, 2015-present

Current Research:
  1. Harnessing Stem Cell Properties for Regenerative Medicine and Development of Stem Cell-related Theranostics: This Program Project has assembled a multidisciplinary team of investigators from academic researchers/physician scientists at CGMH, Academia Sinica, and Development Center for Biotech. We aimto use innovative technology platforms for identification of unique markers and regulators for stem cells and cancer stem cells. In addition, we develop stem cell-related theranostics for regenerative medicine and anti-cancer therapy through collaborations with biotech companies. The platforms developed will also help to develop new methods for cancer detection and therapeutics.Such an interactive team will have expertise complementary to each other and conducive for a cohesive, interrelated team work, to translate the outcome of studies from basic stem cell research into theranostic applications.
  2. Roles of Exosome-associated Glycosphingolipids (GSLs) in Immune Tolerance of Pregnancy: An analogy to the immune suppressive milieu of the host microenvironment in tumor tissues (Stem Cells & Develop.25 1532 2016) is the immune tolerance of pregnancy. However, the events and the key regulators involved in the establishment of a healthy embryo implantation remains a goal only incompletely realized. We expect that GSLs mediated transfer from human microvilli could be incorporated into immune cells and that certain GSLs may facilitate immune tolerance, leading to successful implantation of embryo. Specifically, we employ our state of the art mass spec. technology to explore an innovative concept concerning the embryo/endometrium crosstalk. Through such endeavors, our studies will likely provide a roadmap for heretofore un-chartered territory of research regarding the involvement of GSLs in early embryogenesis and the key regulators involved in the establishment of a healthy pregnancy.
  3. Structure-Based Design for Binding Peptides in Anti-Cancer Therapy: The conventional anticancer therapeutics usually lack cancer specificity, leading to damage of normal tissues. Ideally, anticancer therapeutics carrying payloads of drugs equipped with cancer targeting peptides can act like “guided missiles” with the capacity of targeted delivery toward many types of cancers. Peptides are amenable for conjugation to many payloads for functionalization, thereby improving drug delivery and cellular uptake in cancer-targeting therapies (Biomaterials 2018, 156 1-15). In our studies, the development and application of strategies for structure-based design of cancer-targeting peptides against GRP78 are explored through molecular docking and in silico analysis. We investigate the peptide pharmacokinetics and targeting delivery, including molecular docking studies, features that provide advantages for in vivo use, and properties that influence the cancer-targeting ability. Currently, we are developing newanti-cancer therapeutics conjugated with this cancer targeting peptides.
  4. Glycoprotein Dysfunctions in Lung Stem Cells(LSCs) and Disease Disorders: We have deciphered glycoprotein profiling of lung cells and identified surface markers for isolation of LSCs (Nat Nanotechnol. 8: 682 2013). We found that Fut8 (α1,6-fucosyltransferase) activity was expressedabundantlyin LSCs. In addition, we developedan organotypic culture for lung alveologenesis to examine if diminished core fucosylation recapitulate the structural changes frequently observed in chronic obstructive pulmonary disease (COPD). We have also developed a robust and quantitative site-specific MS proteomic platform to analyze alterations of core-fucosylation and have observed specific alterations at 355 core-fucosylation sites in LSCsafter Fut8 knockdown. Currently, we are investigating a few candidate proteins with altered core fucosylations which lead to the dysfunctionalalveologenesis in site-specific manner for lung disorders.
  5. Disease-derived Induced Pluripotent Stem Cells (iPSCs) and Genome Editing:Specifically, we provide: (i) platform for physician scientists at CGMH to generate iPSCs from patients of his/her choice for disease modeling; (ii) platform to characterize and validate the generated iPSCs for full reprogramming; (iii) help to differentiate iPSCs into neuronal, cardiomyocytes, and hepatic pathwaysin lineage-specific manner; and (iv) technology of genome editing with CRISPR to create isogenic iPSC lines that carry mutations in diseases. Furthermore, we have generated an isogenic pair of iPSCs derived from normal and early onset Alzheimer’s disease (AD) with D678H mutation in APP gene via genome editing to assess early prodromal changes before the onset of disease.
  6. Comparative Evolutionary Genomics Revealed Novel Proteins Important for Various New Functions: For example, we first identified a novel Protein, Puf-A in zebrafish, which plays important roles in the formation of germ cell lineage. Current studies further showed that the expression of Puf-A is not only upregulated in advanced human lung cancer, but also is highly prognostic for stage I lung cancer. Mechanistically, Puf-A interacts with 5.8S pre-rRNA and maintains the integrity of 90S pre-ribosomes, thereby impacting early ribosome assembly. Silencing of Puf-A disrupts the assembly of 90S pre-ribosomes and induces the translocation of nucleophosmin (NPM1), resulting in impairment of ribosome synthesis. Thus, Puf-A is crucial for over-activation of ribosome biogenesis and contributes to tumor progression and cancer growth. sent

Publications:

  1. Wu T.J., Tzeng Y.K., Chang W.W., Cheng C.A., Kuo Y., Chien C.H., Chang H.C., Yu J.* Tracking the engraftment and regenerative capabilities of transplanted lung stem cells using fluorescent nanodiamonds. Nat Nanotechnol 2013, 8(9): 682-689.
  2. Wang S.H., Wu Y.T., Kuo S.C., Yu J.* HotLig: a molecular surface-directed approach to scoring protein-ligand interactions. J ChemInf Model 2013, 53(8): 2181-2195.
  3. Chang W.W., Lin R.J., Yu J., Chang W.Y., Fu C.H., Lai A.C., Yu J.C., Yu A.L.* The expression and significance of insulin-like growth factor-1 receptor and its pathway on breast cancer stem/progenitors. Breast Cancer Res 2013, 15(3): R39.
  4. Fu C.H., Lin R.J., Yu J., Chang W.W., Liao G.S., Chang W.Y., Tseng L.M., Tsai Y.F., Yu J.C., Yu A.L. A Novel Oncogenic Role of Inositol Phosphatase SHIP2 in ER-Negative Breast Cancer Stem Cells: Involvement of JNK/Vimentin Activation. Stem Cells 2014, 32(8): 2048-2060.
  5. Lin C.W., Sun M.S., Liao M.Y., Chung C.H., Chi Y.H., Chiou L.T., Yu J., Lou K.L., Wu H.C. Podocalyxin-like 1 promotes invadopodia formation and metastasis through activation of Rac1/Cdc42/cortactin signaling in breast cancer cells. Carcinogenesis 2014, 35: 2425-35.
  6. Lin J.J., Huang C.S., Yu J., Liao G.S., Lien H.C., Hung J.T., Lin R.J., Chou F.P., Yeh K.T., Yu A.L.* Malignant phyllodes tumors display mesenchymal stem cell features and aldehyde dehydrogenase/disialoganglioside identify their tumor stem cells. Breast Cancer Research 2014, 16(2): R29.
  7. Cheng J.Y., Wang S.H., Lin J., Tsai Y.C., Yu J., Wu J.C., Hung J.T., Lin J.J., Wu Y.Y., Yeh K.T., Yu A.L.* Globo-H ceramide shed from cancer cells triggers translin-associated factor X-dependent angiogenesis. Cancer Research 2014, 74:6856-66.
  8. Chen E., Yu J.* Epigenetic disruptions of histone signatures for the trophectoderm and inner cell mass in mouse parthenogenetic embryos. Stem Cells and Development 2015, 24:550-64.
  9. Wang S.H., Lee A.C., Chen I.J., Chang N.C., Wu H.C., Yu H.M., Chang Y.J., Lee T.W., Yu J.C., Yu A.L.*, Yu J.* Structure-based optimization of GRP78-binding peptides that enhances efficacy in cancer imaging and therapy. Biomaterials 2016, 94:31-44.
  10. Wang S.H., Yu J.* Data for peptide-binding assay with oriented immobilization of GRP78 in Biacore. Data in Brief 2016, 7:1696-1699.
  11. Ho M.Y., Yu A.L., Yu J.* Glycosphingolipid dynamics in human embryonic stem cell and cancer: their characterization and biomedical implications. Glycoconjugate Journal 2016, doi:10.1007/s10719-016-9715-x.
  12. Tan K.P., Ho M.Y., Cho H.C., Yu J., Hung J.T., Yu A.L.* Fucosylation of LAMP-1 and LAMP-2 by FUT1 correlates with lysosomal positioning and autophagic flux of breast cancer cells. Cell Death & Disease 2016, 7(8): e2347.
  13. Yu A.L., Hung J.T., Ho M.Y., Yu J.* Alterations of glycosphingolipids in embryonic stem cell differentiation and development of glycan-targeting cancer immunotherapy. Stem Cells & Development 2016, 25(20): 1532-1548.
  14. Hung J.T., Sawant R.C., Wang S.H., Huang J.R., Huang C.L., Yang S.A., Shelke G.B., Yu J., Yu A.L., Luo S.Y.* Structure-based design of NH-modified α-galactosyl ceramide (KRN7000) analogues and their biological activities. ChemistrySelect 2016, 1:4564-69.
  15. Chiu H.Y., Lin C.H, Hsu C.Y., Yu J.*, Hsieh C.H.*, Shyu W.C.* IGF1R+ dental pulp stem cells enhanced neuroplasticity in hypoxia-ischemia model. Mol. Neurobiol., 2016. DOI 10.1007/s12035-016-0210-y.
  16. Wu T.J., Chiu H.Y., Yu J.* Fluorescent nanodiamonds for tracking the engraftment and repair of lung stem cells. In Nanotechnologies in Preventive and Regenerative Medicine, Chapter 14. Elsevier Publisher, Oxford, United Kingdom, 2017.
  17. Liang Y.J., Wang C.Y., Wang I.A., Chen Y.W., Li L.T., Lin C.Y., Ho M.Y., Chou T.L., Wang Y.H., Chiou S.P., Lin Y.J., Yu J.* Interaction of glycosphingolipids GD3 and GD2 with growth factor receptors maintains breast cancer stem cell phenotype. Oncotarget 2017, 8(29):47454-73.
  18. Kuo H.H., Lin R.J., Hung J.T., Hsieh C.B., Hung T.H., Lo F.Y., Ho M.Y., Yeh C.T., Huang Y.L., Yu J.*, Yu A.L.* High expression FUT1 and B3GALT5 is an independent predictor of postoperative recurrence and survival in hepatocellular carcinoma. Scientific Reports 2017, 7:10750.
  19. Wang S.H., Yu J.* Structure-based design for binding peptides in anti-cancer therapy. Biomaterials 2018, 156 1-15.
  20. Liao C.H., Chang W.W., Yang B.C., Wang Y.H., Liu W.L., Yu A.L., Yu J.* Leucine-rich Repeat Neuronal Protein 1 Regulates Differentiation of Human Embryonic Stem Cells by Posttranslational Modifications of Pluripotency Factors. Stem Cells 2018 (in press).
  21. Tsai C.T., Kuo M.W., Lin J.L., Yu A.L., Yu J.* Deficiency of a Novel Gene, Yulink, Predisposes to Heart Failure and Ventricular Arrhythmia. 2017, submitted.
  22. Cho H.C., Lai L.C., Huang Y.L., Wang S.H., Cho I.M., Kuo M.W., Cheng P.Y., Ho M.Y., Liu Y.H., Lin R.J., Yu A.L., Yu J.* Puf-A, a novel 5.8S ribonucleoprotein of 90S pre-ribosome, links ribosome biogenesis to cancer progression. 2017, submitted.