John Yu, M.D., Ph.D.

Appointments：Distinguished Chair Professor and Director

Lab：Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital, Linkou

Education：M.D. / Ph.D. Biophysics

School/Nation：National Taiwan University, School of medicine/ University of Chicago

Tel: 03-3281200 #5218

E-mail: johnyu@cgmh.org.tw

Research website: http://www1.cgmh.org.tw/intr/intr2/c33a0/cgmh/homepage/e_stemcell_2.html

研究室現有： 博士後研究員  17人

博士班研究生    2人

碩士班研究生    0人

專任研究助理    6人

大學部專題生    0人

Research Interest: Stem cell biology; Regulation of hematopoiesis; Tumorigenesis

Research Synopsis: The objective of our research is to garner a better understanding of stem cells and cancer, and translate to regenerative medicine and cancer therapy. By integrating scientific discoveries with clinical resources of CGMH at Linkou, we also aim to develop new diagnostic tools and novel therapeutic strategies for patients. We use innovative technology platforms for identification of unique markers and regulators for human embryonic stem cells (hESCs) or cancer stem/initiating cells (CSCs). Specifically, we employ glycomics/glycoproteomics, stem cell biology, and iPSC technology coupled with genome editing, to interrogate differential profiles of glycans/glycoproteins in stem cells and their downstream regulatory control. Launching from our newly found markers of hESCs or CSCs, and recent isolation of lung stem cells (LSCs), we focus on (a) the role of their specific surface markers (e.g., glycosphingolipids, N-linked sialoglycoproteins, phosphoproteins, etc.), downstream regulators, and selected glycosyltransferases in the maintenance of the self-renewal and differentiation potentials, (b) the inter-relationship between stem cells and cancers, (c) the potential contribution of glycans to the functions and differentiation capacity of stem cells, and (d) new strategies for investigating the functions and emphysema formation of alveolar LSCs during branching morphogenesis, as well as the possible involvement of type 2 epithelial-mesenchymal transition in promoting small airway fibrosis. On one hand, the current research should help to sort out from the newly found surface markers that will facilitate the isolation and expansion of stem cells and CSCs, and also help to shed light on the functional roles of these new molecules in stem cells and cancer. On the other hand, the innovative technology platforms developed will not only promote our understanding of the relationship between stem cells and cancers, but also foster the development of cancer detection and therapeutics targeting new glycans/ glycoproteins.

Publications:

Selected Recent Relevant Publications (Selected from 113 publications):

1.  Ling, T.Y., Kuo, M.D., … Chen, S.H. and Yu, J. (2006) Identification of pulmonary Oct-4+ stem/progenitor cells and demonstration of their susceptibility to SARS-CoV infection in vitro. PNAS USA, 103: 9530-9535.

2.  Daley, G.Q., Ahrlund-Richter, L., … Yu, J., et al. (2007) The ISSCR guidelines for human embryonic stem cell research. Science, 315:603-604 with 64 pages of supplementary online materials.

3.  Chang, W.W., Lee, C.H., Lee, P., Lin, J., Hsu, C.W., Hung, J.T., Lin, J.J., Yu, J.C., Shao, L.E., Yu, J., Wong, C.H., and Yu, A.L. (2008) Expression of Globo H and SSEA3 in breast cancer stem cells and the involvement of fucosyl transferases 1 & 2 in Globo H synthesis. PNAS USA, 105: 11667-11672.

4.  Kuo, M.W., Wang, S.H., Chang, J.C., …, Li, W.H. and Yu, J. (2009) A novel puf-A gene predicted from evolutionary analysis is involved in the development of eyes and primordial germ-cells. PloS One 4: e4980.

5.  Andrews, P. W., Arias-Diaz, J., Auerbath, J., … Yu, J., et al. (2009) Consensus guidance for banking and supply of human embryonic stem cell lines for research purposes- international cell banking initiative. Stem Cell Rev. 5:301-314.

6.  Lu T.Y., Lu R.M., Liao M.Y., Yu J., Chung C.H., Kao C.F, and Wu H.C. (2010) Epithelial cell adhesion molecule regulation is associated with the maintenance of the undifferentiated phenotype of human embryonic stem cells. J. Biol. Chem., 285: 8719-8732.

7.  Huang, C.J., …, Yu, J.* and Chang Y.C.* (2010) The influence of collagen film nanostructure on pulmonary stem cells and collagen-stromal cell interactions. (*Co-corresponding authors) Biomaterials, 31:8271-8280.

8.  Liang, Y. J.; Kuo, H. H.; Lin, C. H.; Chen, Y. Y.; Yang, B. C.; Cheng, Y. Y.; Yu, A. L.; Khoo, K. H.; Yu, J. (2010) Switching of the core structures of glycosphingolipids from globo- and lacto- to ganglio-series upon human embryonic stem cell differentiation. PNAS USA, 107: 22564-22569.

9.  Cheng, P.Y., Lin, Y.P., Chen, Y.L., Lee, Y.C., Tai, C.C., Wang, Y.T., Chen, Y.J., Kao, C.F., and Yu, J. (2011) Interplay between SIN3A and STAT3 mediates chromatin conformational changes and GFAP expression during cellular differentiation. PLos One, 6: e22018.

10. Liang, Y.J., Yang, B.C., Chen, J.M., Lin, Y.H., Huang, C.L., Cheng, Y.Y., Hsu, C.Y., Khoo, K.H., Shen, C.N., Yu, J. (2011) Changes in glycosphingolipid composition during differentiation of human embryonic stem cells to ectodermal or endodermal lineages. Stem Cells, 29: 1995-2004.

11. Cho, H.C., Lai, C.Y., Shao, L.E., and Yu, J. (2011) Identification of tumorigenic cells in KrasG12D-induced lung adenocarcinoma. Cancer Research, 71:7250-7258.

12. Liao, C.H. and Yu, J. (2012) Human embryonic stem cell differentiation: role of glycosphingolipid structure. Volume 8: p179- 190 “Stem cells and cancer stem cells” (Editor: M. A. Hayat; Springer London) 

13. Chen, Y.H. and Yu, J. (2012) Ectopic expression of Fgf3 leads to aberrant lineage segregation in the mouse parthenote preimplantation embryos. Developmental Dynamics, 241: 1651-1664. 

14. Cho, H.C., Liao, C.H., Yu, A.L. and Yu, J. (2012) Surface markers in stem cells and cancer from the perspective of glycomic analysis. International J. of Biol. Markers, 27(4): 344-352; a review

15. Chang, W.W., Lin, R.J., Yu, J., Chang, W.Y., Fu, C.H., Lai, A. C, Yu, J.C. and Yu, A. L. (2013) The expression and significance of insulin-like growth factor-1 receptor and its pathway on breast cancer stem cells/progenitors. Breast Cancer Research, 15(3):R39

16. Wang, S.H., Wu, Y.T., Kuo, S.C., and Yu, J. (2013) HotLig: a molecular surface-directed approach to scoring protein-ligand interactions. Journal of Chemical Information and Modeling, 53:2181–2195.

17. Wu, T.J., Tzeng, Y.K., Chang, W.W., Cheng, C.A., Kuo, Y., Chien, C.H., Chang, H.C. and Yu, J. (2013) Tracking the engraftment and regenerative capabilities of transplanted lung stem cells using fluorescent nanodiamonds. Nature Nanotechnology, 8:682-689.

18. 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. and Yu, A.L. (2014) Malignant phyllodes tumors display mesenchymal stem cell features and ALDH/GD2 identify their tumor stem cells. Breast Cancer Research, 16:R29.

19. 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. and Yu, A.L. (2014) Oncogenic role of SH2-containing-5’-inositol phosphatase-2 in breast cancer stem cells. Stem Cells, 32(8): 2048-60.

20. 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. (2014) Podocalyxin-like 1 promotes invadopodia formation and metastasis through activation of Rac1/Cdc42/cortactin signaling in breast cancer cells. Carcinogenesis, 35: 2425-35.

21. 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. (2014) Globo-H ceramide shed from cancer cells triggers translin-associated factor X-dependent angiogenesis. Cancer Research, 74:6856-66.

22. Chen, E., Yu, J. (2014) Epigenetic disruptions of histone signatures for the trophectoderm and inner cell mass in mouse parthenogenetic embryos. Stem Cells and Development, 24:550-64.