Lu, Joyce Jean 呂仁

副研究員


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Telephone: 02-2789-9580#602
[ CV ]

 

 

EDUCATION AND POSITIONS HELD:

  • Associate Professor, Stem Cell Program, Genomics Research Center, Academia Sinica, Taiwan. 2015-present
  • Assistant Professor, Stem Cell Program, Genomics Research Center, Academia Sinica, Taiwan. 2007-2015
  • Adjunct Assistant Professor, Genomics and System Biology Program, College of Life Science, National Taiwan University, Taiwan. 2010-present
  • Co-PI, National RNAicore Facility Plateform, 2009-present
  • Postdoctoral Fellow/Associate, Molecular, Department of Cellular, and Developmental Biology, Yale University, USA. 2003-2007
  • Postdoctoral Fellow, Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taiwan. 2001-2003
  • Ph.D. Institute of Microbiology, National Taiwan University, Taipei, Taiwan. 1995-2000
  • M.S. Institute of Molecular Medicine, National Taiwan University, Taipei, Taiwan. 1992-1994
  • B.S. Department of Medical Technology, National Taiwan University, Taipei, Taiwan. 1988-1992
  • Research Assistant, Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taiwan. 1994-1995

HONORS:

  • Ruth L. Kirschstein National Research Service Award, 2003-2004, NIH
  • Outstanding Paper Award, National Taiwan University, 2002

RESEARCH INTERESTS:

High throughput functional screens pinpoints key factors for cell fate determination

Lu-scheme  Research Figure/Table/Scheme

Stem cell renewal and differentiation is important for stem cell biology and regenerative medicine. To efficiently pinpoint factors critical for cell fate determination, systematically functional screens were performed in mouse embryonic stem cells (ESCs), human ESCs, and mesenchymal stem cells (MSCs). We established the first shRNA screen in ESCs. With a shRNA library of kinases and phosphatases contains 4796 shRNAs, we identified 244 genes essential for ESC renewal. Among them, Nme6 and Nme7 is essential for 8 stemness genes expressions. With 517 shRNAs target genes are differentially expressed in undifferentiated human ESCs and differentiated cells or are embryonic lethal, we performed a shRNA functional screen and found 86 genes essential for human ESC renewal. And two candidate genes either bridge the oxidation and reduction status of ESCs with stemness signals, or block neural stem cell differentiation are currently studied in-depth. To fulfill the unmet need of bone diseases, a gain-of-function screen was performed with an overexpression library contains 12380 genes. 9 candidate genes are found to be essential and sufficient to promote the osteogenesis of human MSCs. By this method, we found soluble factor that can completely treat and prevent osteoporosis. Thus we found many factors play critical roles for ESC and MSC renewal and differentiation by systematically functional screens.

對幹細胞生物學和再生醫學來說,幹細胞的自我更新與分化是很重要的。為了有效地找尋決定細胞的命運的樞紐因子,我們在小鼠胚胎幹細胞,人類胚胎幹細胞,和間質幹細胞進行系統性功能篩選。我們建立了第一個在胚胎幹細胞的shRNA篩選。我們以4796個shRNA進行激酶和磷酸酶的功能性篩選,並發現了244個基因對胚胎幹細胞的自我更新是必要的。其中,Nme6和Nme7對8個幹細胞特性基因的表達是必需的。我們另以在未分化的胚胎幹細胞和分化細胞差異表現基因或對胚胎致死基因所設計的517個 shRNA,在人類胚胎幹細胞進行功能性篩選。我們發現有86個基因對人類胚胎幹細胞的自我更新是必要的。目前針對其中有兩個候選基因正在進行進一步的研究。這兩個候選基因可連結胚胎幹細胞特性訊息與細胞氧化還原狀態,或阻止神經幹細胞的分化。為了解決骨骼疾病中待解決的問題,在我們在間質幹細胞過度表達12380個基因。至少有9個候選基因被發現對成骨作用是必要的,且過度表達這些基因足以促進間質幹細胞的成骨作用。藉由這個方法,我們發現可溶性因子可以完全地治療與預防骨質疏鬆症。因此,透過系統性功能篩選,我們發現許多樞紐因子在胚胎幹細胞和間質幹細胞的自我更新與分化扮演關鍵性的角色。

SELECTED PUBLICATIONS:

  • Yang SC, Liu JJ, Wang CK, Lin YT, Tsai SY, Chen WJ, Huang WK, Tu PA, Lin YC, Chang CF, Cheng CL, Lin H, Lai CY, Lin CY, Lee YH, Chiu YC, Hsu CC, Hsu SC, Hsiao M, Schuyler SC, Lu FL*, Lu J*, accepted, “Down-regulation of ATF1 leads to early neuroectoderm differentiation of human embryonic stem cells by increasing the expression level of SOX2.”, The FASEB Journal: official publication of the Federation of American Societies for Experimental Biology, 33(9),10577-10592. (SCIE) (IF: 5.595; SCIE ranking: 9.4%,22.1%,14.3%)
  • Wang, C.H., Ma, N., Lin, Y.T., Wu, C.C., Wu, H. J., Yu, C.C., Hsiao, M., Lu, F.L., Schuyler, S.C., and Lu, J*., accepted, Current Protocols in Stem Cell Biology, 26: 5C.3.1 - 5C.3.x. pages, Hoboken, NJ,USA: Wiley-Blackwell.
  • Cheng Chih-Lun, Yang Shang-Chih, Lai Chien-Ying, Wang Cheng-Kai, Chang Ching-Fang, Lin Chun-Yu, Chen Wei-Ju, Lin Po-Yu, Wu Han-Chung, Ma Nianhan, Lu Frank Leigh*, Lu Jean*, 2020, “CXCL14 Maintains hESC Self-Renewal through Binding to IGF-1R and Activation of the IGF-1R Pathway”, Cells, 9(7) 1706. (SCIE) (IF: 4.829; SCIE ranking: 28.9%)
  • Nguyen Mai-Huong Thi, Lin Chen-Huan, Liu Szu-Mam, Miyashita Azusa, Ihn Hironobu, Lin Hsuan, Ng Chi Hou, Tsai Jen-Chieh, Chen Ming-Hong, Tsai Mu-Shiun, Lin In-Yu, Liu Shu-Chen, Li Long-Yuan, Fukushima Satoshi*, Lu Jean*, Ma Nianhan*, 2020, “miR-524-5p reduces the progression of the BRAF inhibitor-resistant melanoma”, Neoplasia, 22(12) 789-799. (SCIE) (IF: 4.994; SCIE ranking: 22.4%)
  • Lai Pei‑Lun, Chen Ting‑Chun, Feng Chun‑Yen, Lin Hsuan, Ng Chi‑Hou, Chen Yun, Hsiao Michael, Lu Jean*, Huang Hsiao‑Chun*, 2020, “Selection of a malignant subpopulation from a colorectal cancer cell line”, Oncology Letters, 20(3) 2937-2945. (SCIE) (IF: 1.664; SCIE ranking: 87%)
  • Kuan II, Lee CC, Chen CH, Lu J, Kuo YS, Wu HC, 2019, “The extracellular domain of epithelial cell adhesion molecule (EpCAM) enhances multipotency of mesenchymal stem cells through EGFR-LIN28-LET7 signaling.”, The Journal of biological chemistry, 294(19), 7769-7786. (SSCI) (IF: 4.011; SSCI ranking: 24%)
  • Chang HC, Huang PH, Syu FS, Hsieh CH, Chang SL, Lu J*, Chen HC*, 2018, “Critical involvement of atypical chemokine receptor CXCR7 in allergic airway inflammation.”, Immunology, 154(2), 274-284. (SCIE) (IF: 3.701; SCIE ranking: 35.8%)
  • Liu SM, Lin CH, Lu J, Lin IY, Tsai MS, Chen MH, Ma N, 2018, “miR-596 Modulates Melanoma Growth by Regulating Cell Survival and Death.”, The Journal of investigative dermatology, 138(4), 911-921. (SCIE) (IF: 6.287; SCIE ranking: 3.2%)
  • Wang CK, Yang SC, Hsu SC, Chang FP, Lin YT, Chen SF, Cheng CL, Hsiao M, Lu FL, Lu J*, 2017, “CHAC2 is essential for self-renewal and glutathione maintenance in human embryonic stem cells.”, Free radical biology & medicine, 113, 439-451. (SCIE) (IF: 5.606; SCIE ranking: 14.5%,12.3%)
  • Lai PL, Lin H, Chen SF, Yang SC, Hung KH, Chang CF, Chang HY, Lu FL, Lee YH, Liu YC, Huang HC*, Lu J*, 2017, “Efficient Generation of Chemically Induced Mesenchymal Stem Cells from Human Dermal Fibroblasts.”, Scientific reports, 7, 44534. (SCIE) (IF: 4.259; SCIE ranking: 15.6%)
  • Lin YT, Wang CK, Yang SC, Hsu SC, Lin H, Chang FP, Kuo TC, Shen CN, Chiang PM, Hsiao M, Lu FL, Lu J*, 2017, “Elimination of undifferentiated human embryonic stem cells by cardiac glycosides.”, Scientific reports, 7(1), 5289. (SCIE) (IF: 4.259; SCIE ranking: 15.6%)
  • Kuan II, Liang KH, Wang YP, Kuo TW, Meir YJ, Wu SC, Yang SC, Lu J*, Wu HC*, 2017, “EpEX/EpCAM and Oct4 or Klf4 alone are sufficient to generate induced pluripotent stem cells through STAT3 and HIF2alpha.”, Scientific reports, 7, 41852. (SCIE) (IF: 4.259; SCIE ranking: 15.6%)
  • Hsieh MH, Chen YT, Chen YT, Lee YH, Lu J, Chien CL, Chen HF, Ho HN, Yu CJ, Wang ZQ, Teng SC, 2017, “PARP1 controls KLF4-mediated telomerase expression in stem cells and cancer cells.”, Nucleic acids research, 45(18), 10492-10503. (SCIE) (IF: 10.162; SCIE ranking: 4.8%)
  • Chang WF, Hwu YM, Xu J, Lin CJ, Wang SW, Cheng AS, Lu J, Lu CH, Sung LY, 2016, “Derivation of Patient Specific Pluripotent Stem Cells Using Clinically Discarded Cumulus Cells.”, PloS one, 11(11), e0165715. (SCIE) (IF: 2.806; SCIE ranking: 23.4%)
  • Huang YC, Lin SJ, Lin KM, Chou YC, Lin CW, Yu SC, Chen CL, Shen TL, Chen CK,Lu J, Chen MR, Tsai CH, 2016, “Regulation of EBV LMP1-triggered EphA4 downregulation in EBV-associated B lymphoma and its impact on patients\' survival.”, Blood, 128(12), 1578-89. (SCIE) (IF: 13.164; SCIE ranking: 2.9%)
  • Chang JS, Su CY, Yu WH, Lee WJ, Liu YP, Lai TC, Jan YH, Yang YF, Shen CN, Shew JY, Lu J, Yang CJ, Huang MS, Lu PJ, Lin YF, Kuo ML, Hua KT, Hsiao M, 2015, “GIT1 promotes lung cancer cell metastasis through modulating Rac1/Cdc42 activity and is associated with poor prognosis.”, Oncotarget, 6(34), 36278-91. (SCIE) (IF: 5.168; SCIE ranking: 20.3%,25.3%)
  • Chua HH, Tsuei DJ, Lee PH, Jeng YM, Lu J, Wu JF, Su DS, Chen YH, Chien CS, Kao PC, Lee CN, Hu RH, Ni YH, Chang MH, 2015, “RBMY, a novel inhibitor of glycogen synthase kinase 3beta, increases tumor stemness and predicts poor prognosis of hepatocellular carcinoma.”, Hepatology, 62(5), 1480-96. (SCIE) (IF: 13.246; SCIE ranking: 5.1%)
  • Wu, C. C., Wu, H.C., Chen, W.J, Wang, C.H, Lin, C.H., Hsu, S.C., Chen, Y.R., Hsiao, M., Schuyler, S.C., Lu, F. L. , Ma, N.H., and Lu, J.*., 2015, “Suppression of Dual leucine zipper-bearing Kinase activity by Akt is required for mouse embryonic stem cell self-renewal”, CELL CYCLE, 14(8), 1207-1217. (SCIE) (IF: 3.304; SCIE ranking: 51.1%)
  • Chang, C.F., Hsu, K.H., Shen, C.N., Li, C.L.*, and Lu, J.*, 2014, “Enrichment and characterization of two subgroups of committed osteogenic cells in the mouse endosteal bone marrow with expression levels of CD24”, Journal of Bone Research, 2, 144.
  • Huang HN, Chen SY, Hwang SM, Su MW, Mai W, Wang HW, Cheng WC, Schuyler SC, Ma N, Lu FL, Lu, J.*, 2014, “miR-200c and GATA binding protein 4 regulate human embryonic stem cell renewal and differentiation”, Stem Cell Research, 12(2), 338-353. (SCIE) (IF: 3.902; SCIE ranking: 38.9%,41.7%,21.1%)
  • Liu YC, Kao YT, Huang WK, Lin KY, Wu SC, Hsu SC, Schuyler SC, Li LY, Leigh Lu F, Lu J*, 2014, “CCL5/RANTES is important for inducing osteogenesis of human mesenchymal stem cells and is regulated by dexamethasone.”, Bioscience trends, 8(3), 138-143. (SCIE) (IF: 1.844; SCIE ranking: 41.2%)
  • Liu SM, Lu J, Lee HC, Chung FH, Ma N, 2014, “miR-524-5p suppresses the growth of oncogenic BRAF melanoma by targeting BRAF and ERK2.”, Oncotarget, 5(19), 9444-9459.
  • Yang YF, Jan YH, Liu YP, Yang CJ, Su CY, Chang YC, Lai TC, Chiou J, Tsai HY, Lu J, Shen CN, Shew JY, Lu PJ, Lin YF, Huang MS, Hsiao M, 2014, “Squalene synthase induces tumor necrosis factor receptor 1 enrichment in lipid rafts to promote lung cancer metastasis.”, American journal of respiratory and critical care medicine, 190(6), 675-687. (SCIE) (IF: 15.239; SCIE ranking: 3.3%,6.1%)
  • Liu YP, Yang CJ, Huang MS, Yeh CT, Wu AT, Lee YC, Lai TC, Lee CH, Hsiao YW, Lu J, Shen CN, Lu PJ, Hsiao M, 2013, “Cisplatin Selects for Multidrug-Resistant CD133+ Cells in Lung Adenocarcinoma by Activating Notch Signaling.”, Cancer Research, 73(1), 406-416. (SCIE) (IF: 9.13; SCIE ranking: 7.6%)
  • Chen HW, Chen HY, Wang LT, Wang FH, Fang LW, Lai HY, Chen HH, Lu J, Hung MS, Cheng Y, Chen MY, Liu SJ, Chong P, Lee OK, Hsu SC, 2013, “Mesenchymal stem cells tune the development of monocyte-derived dendritic cells toward a myeloid-derived suppressive phenotype through growth-regulated oncogene chemokines.”, Journal of Immunology, 190(10), 5065-5077. (SCIE) (IF: 4.539; SCIE ranking: 25.2%)
  • Lu FL, Yu CC, Chiu HH, Liu HE, Chen SY, Lin S, Goh TY, Hsu HC, Chien CH, Wu HC, Chen MS, Schuyler SC, Hsieh WS, Wu MH, Lu J*, 2013, “Sonic hedgehog antagonists induce cell death in acute myeloid leukemia cells with the presence of lipopolysaccharides, tumor necrosis factor-alpha, or interferons.”, Investigational New Drugs, 31(4), 823-832. (SCIE) (IF: 3.502; SCIE ranking: 41.3%,24.5%)
  • Wang CH, Ma N, Lin YT, Wu CC, Wu HJ, Yu CC, Hsiao M, Lu FL, Schuyler SC, and Lu, J*, 2013, “UNIT 5C.3 Array-based high-throughput screening in mouse embryonic stem cells with shRNAs”, Current Protocols in Stem Cell Biology, 26: 5C.3.1-5C. 3.19.
  • Wang, C. H., Ma, N. H., Lin, Y.T., Wu, C.C., Hsiao M., Lu, F. L., Yu, C.C., Chen, S.Y., and Lu, J.*, 2012, “A shRNA functional screening in embryonic stem cells reveals Nme6 and Nme7 signaling are crucial for stem cell renewal”, Stem Cells, 30(10), 2199-2211. (SCIE) (IF: 5.587; SCIE ranking: 16.7%,14.1%,17.9%,23.2%,9.3%)
  • Chou YC, Chen CL, Yeh TH, Lin SJ, Chen MR, Doong SL, Lu J, Tsai CH, 2012, “Involvement of recepteur d'origine nantais receptor tyrosine kinase in Epstein-Barr virus-associated nasopharyngeal carcinoma and its metastasis.”, The American Journal of Pathology, 181(5), 1773-1781. (SCIE) (IF: 4.069; SCIE ranking: 16.5%)
  • Chan CC, Cheng LY, Lu J, Huang YH, Chiou SH, Tsai PH, Huo TI, Lin HC, Lee FY, 2012, “The Role of Interferon-gamma Inducible Protein-10 in a Mouse Model of Acute Liver Injury Post Induced Pluripotent Stem Cells Transplantation.”, PLoS One, 7(12), e50577. (SCIE) (IF: 2.766; SCIE ranking: 23.4%)
  • Chou YC, Lin SJ,Lu J, Yeh TH, Chen CL, Weng PL, Lin JH, Yao M, Tsai CH, 2011, “ Requirement for LMP1-induced RON receptor tyrosine kinase in Epstein-Barr virus-mediated B-cell proliferation”, BLOOD, 118(5), 1340-1349. (SCIE) (IF: 15.132; SCIE ranking: 2.8%)
  • Lu J, Hou R, Booth C J, Yang SH and Snyder M, 2006, “Defined culture conditions of human embryonic stem cells”, Proceedings of the national academy of sciences of the united states of america, 103, 5688-5693. (SCIE) (IF: 9.504; SCIE ranking: 7.8%)
  • Lu J, Lin WS, Chen SY , Longnecker R, and Tsai CH, 2006, “Epstein-Barr virus latent membrane protein 2A enhances cell mobility in epithelial cells through syk kinase”, J Biol Chem, 281, 8806-8814. (SCIE) (IF: 4.011; SCIE ranking: 25.6%)
  • Chang Y, Lee HH , Chen YT, Lu J, Wu SY ,Chen CW, Takada K, and Tsai CH , 2006, “Induction of the early growth response 1 gene by Epstein-Barr virus lytic transactivator Zta”, J Virol, 80, 7748-7755. (SCIE) (IF: 4.368; SCIE ranking: 22.9%)
  • Lu J, Chua HH, Chen SY, Chen JY and Tsai CH, 2003, “Regulation of matrix metalloproteinase-1 by Epstein-Barr virus proteins”, Cancer Res, 63, 256-262. (SCIE) (IF: 9.13; SCIE ranking: 7.6%)
  • ChenSY, Lu J, Shih YC and Tsai CH, 2002, “Epstein-Barr virus latent membrane protein 2A regulates c-Jun protein through extracellular signal-regulated kinase”, J Virol, 76, 9556-9561. (SCIE) (IF: 4.368; SCIE ranking: 22.9%)
  • Lu J, Chen SY, Chua HH, Liu YS, Huang YT, Chang Y, Chen JY, Sheen TS, and Tsai CH, 2000, “Upregulation of tyrosine kinase TKT by the Epstein-Barr virus transactivator Zta”, J Virol, 74, 7391-7399. (SCIE) (IF: 4.368; SCIE ranking: 22.9%)
  • Huang YT, Sheen TS, Chen CL, Lu J, Chang Y, Chen JY, and Tsai CH, 1999, “Profile of cytokine expression in nasopharyngeal carcinomas: a distinct expression of interleukin 1 in tumor and CD4+ T cells”, Cancer Res, 59, 1599-1605. (SCIE) (IF: 9.13; SCIE ranking: 7.6%)
  • Chang Y, Tung CH, Huang YT, Lu J, Chen JY, and Tsai CH, 1999, “Requirement for cell-to-cell contact in Epstein-Barr virus infection of nasopharyngeal carcinoma cells and keratinocytes”, J Virol, 73, 8857-8866. (SCIE) (IF: 4.368; SCIE ranking: 22.9%)
  • Chang Y, Sheen TS, Lu J , Huang YT, Chen JY,Yang CS, and Tsai CH, 1998, “Detection of transcripts initiated from two viral promoters (Cp and Wp) in Epstein-Barr virus-infected nasopharyngeal carcinoma cells and biopsies”, Lab Invest, 78, 715-726. (SCIE) (IF: 4.263; SCIE ranking: 15.2%,19.5%)
  • Tsai CH, Liu MT, Chen MR,Lu J, Yang HL,Chen JY and Yang CS, 1997, “Characterization of monoclonal antibodies to the Zta and DNase proteins of Epstein-Barr virus”, J Biomed Sci, 4, 69-77. (SCIE) (IF: 3.466; SCIE ranking: 34.6%,47.9%)