Research
  1. The roles of cullin-RING family ubiquitin ligases in human cancers

    The cullin-RING (CRL) superfamily consists of the largest family of ubiquitin ligases in eukaryotes. Substrate recognition of this family of ubiquitin ligases is achieved by a large set of substrate receptors. A number of substrate receptors are mutated or deregulated in cancers, such as VHL, Fbw7 and Keap1. My laboratory recently identified KLHL20 as a substrate receptor of Cullin3 family ligase. KLHL20 is induced by tumor microenvironment (i.e., hypoxia) and is responsible for ubiquitin-mediated degradation of multiple tumor suppressors, such as DAPK and PML. In addition to KLHL20, we are interested in several other substrate receptors of CRL family ligases that are deregulated in human cancers. Identification of their substrates and determination of functions of these ubiquitination events in tumor formation, progression, and/or tumor stem cell maintenance are current focuses in the lab.

  2. The roles of ubiquitination in autophagy regulation

    Autophagy is an evolutionarily conserved catabolic pathway and participates in diverse physiological processes, such as adaptation to starvation, cell differentiation and development, degradation of aberrant structures, turnover of superfluous or damaged organelles, tumor suppression, innate and adaptive immunity, life span extension and cell death. The role of protein posttranslational modifications in autophagy regulation has emerged. My laboratory recently identified KLHL20 as a critical regulator of autophagy. Current studies are focused on KLHL20-regulated ubiquitination event in autophagy regulation and the physiological significance of this ubiquitination event using cell-based approaches and animal models. In addition, we have employed system biology approaches to identify other ubiquitination events important in autophagy regulation.

Degrees and Positions Held
Positions Held
  • 2012 – present   Distinguished Research Fellow, Institute of Biological Chemistry, Academia Sinica
  • 2011 – 2014   Deputy Director, Institute of Biological Chemistry, Academia Sinica
  • 2006 – 2012   Research Fellow, Institute of Biological Chemistry, Academia Sinica
  • 2003 – 2006   Professor, Institute of Molecular Medicine, College of Medicine, National Taiwan University
  • 1996 – 2003   Associate Professor, Institute of Molecular Medicine, College of Medicine, National Taiwan University
  • 1995 – 1996   Assistant Biochemist, University of California at San Francisco
  • 1992 – 1995   Postdoctoral Fellow, University of California at San Francisco
Degrees
  • 1987 – 1991   Ph.D, Biochemistry, Michigan State University
  • 1983 – 1985   M.S., Biochemistry, National Taiwan University
  • 1979 – 1983   B.S., Agricultural Chemistry, National Taiwan University
Selected Publications
Wang YT, Chen J, Chang CW, Jen J, Huang TY, Chen CM, Shen R, Liang SY, Cheng IC, Yang SC, Lai WW, Cheng KH, Hsieh TS, Lai MZ, Cheng HC, Wang YC, Chen RH
J Clin Invest (2017)
Liu, C.-C., Y.-C. Lin, Y.-H. Chen, C.-M. Chen, L.-Y. Pang, H.-A. Chen, P.-R. Wu, M.-Y. Lin, S.-T Jiang, T.-F. Tai, and R.-H. Chen
Mol Cell (2016)
Yuan, W-C, Y-R Lee, S-Y Lin, J-C Kuo, YP Tan, L-Y Chang, C-H Liu, M-Y Lin, M Xu, Z J Chen, and R-H Chen
Mol Cell (2014)
Lin YC, Lu LT, Chen HY, Duan X, Lin X, Feng XH, Tang MJ, Chen RH
Cancer Research (2014)
Wu, H-C, Y-C Lin, C-H Liu, H-C Chung,Y-T Wang, Y-W Lin, H-I Ma, P-H Tu, SE Lawler, and R-H Chen
Nature Commun (2014)
Chen HY, Lin YM, Chung HC, Lang YD, Lin CJ, Huang J, Wang WC, Lin FM, Chen Z, Huang HD, Shyy JY, Liang JT, Chen RH
Cancer research (2012)
Yuan WC, Lee YR, Huang SF, Lin YM, Chen TY, Chung HC, Tsai CH, Chen HY, Chiang CT, Lai CK, Lu LT, Chen CH, Gu DL, Pu YS, Jou YS, Lu KP, Hsiao PW, Shih HM, Chen RH
Cancer cell (2011)
Wu PR, Tsai PI, Chen GC, Chou HJ, Huang YP, Chen YH, Lin MY, Kimchi A, Chien CT, Chen RH
Cell death and differentiation (2011)
Lin MY, Lin YM, Kao TC, Chuang HH, Chen RH
Journal of cell biology (2011)
Lee Y.-R., W.-C. Yuan, H.-C. Ho, C.-H. Chen, H.-M. Shih, and R.-H. Chen
EMBO J (2010)
Publications List
  1. Lu G, Yi J, Gubas A, Wang YT, Wu Y, Ren Y, Wu M, Shi Y, Ouyang C, Tan HWS, Wang T, Wang L, Yang ND, Deng S, Xia D, (Chen RH), Tooze SA, Shen HM*  (2019-11)  Autophagy  15(11), 1917-1934  "Suppression of autophagy during mitosis via CUL4-RING ubiquitin ligases-mediated WIPI2 polyubiquitination and proteasomal degradation."
  2. (Chen RH), Chen YH, Huang TY  (2019-10)  Journal of biomedical science  26(1), 80  "Ubiquitin-mediated regulation of autophagy."
  3. Chen FY, Huang MY, Lin YM, Ho CH, Lin SY, Chen HY, Hung MC, (Chen RH)  (2019-09)  Journal of Cell Biology  218(9), 3002-3018  "BIK ubiquitination by the E3 ligase Cul5-ASB11 determines cell fate during cellular stress."
  4. Tan BS, Yang MC, Singh S, Chou YC, Chen HY, Wang MY, Wang YC, (Chen RH*)  (2019-07)  ONCOGENE  38(28), 5612–5626  "LncRNA NORAD is repressed by the YAP pathway and suppresses lung and breast cancer metastasis by sequestering S100P."
  5. Chen HY, Lang YD, Lin HN, Liu YR, Liao CC, Nana AW, Yen Y, (Chen RH)  (2019-07)  Scientific reports  9(1), 9687  "miR-103/107 prolong Wnt/beta-catenin signaling and colorectal cancer stemness by targeting Axin2."
  6. Huang HH, Chen FY, Chou WC, Hou HA, Ko BS, Lin CT, Tang JL, Li CC, Yao M, Tsay W, Hsu SC, Wu SJ, Chen CY, Huang SY, Tseng MH, Tien HF, (Chen RH)  (2019-06)  BMC cancer  19(1), 617  "Long non-coding RNA HOXB-AS3 promotes myeloid cell proliferation and its higher expression is an adverse prognostic marker in patients with acute myeloid leukemia and myelodysplastic syndrome."
  7. Lee YR, Chen M, Lee JD, Zhang J, Lin SY, Fu TM, Chen H, Ishikawa T, Chiang SY, Katon J, Zhang Y, Shulga YV, Bester AC, Fung J, Monteleone E, Wan L, Shen C, Hsu CH, Papa A, Clohessy JG, Teruya-Feldstein J, Jain S, Wu H, Matesic L, (Chen RH), Wei W, Pandolfi PP*  (2019-05)  SCIENCE  364(6441), eaau0159  "Reactivation of PTEN tumor suppressor for cancer treatment through inhibition of a MYC-WWP1 inhibitory pathway."
  8. Liang KH, Tso HC, Hung SH, Kuan II, Lai JK, Ke FY, Chuang YT, Liu IJ, Wang YP, (Chen RH), Wu HC  (2018-10)  Cancer letters  433, 165-175  "Extracellular domain of EpCAM enhances tumor progression through EGFR signaling in colon cancer cells."
  9. Yeh HW, Hsu EC, Lee SS, Lang YD, Lin YC, Chang CY, Lee SY, Gu DL, Shih JH, Ho CM, Chen CF, Chen CT, Tu PH, Cheng CF, (Chen RH), Yang RB, Jou YS  (2018-04)  Nature cell biology  20(4), 479-491  "PSPC1 mediates TGF-beta1 autocrine signalling and Smad2/3 target switching to promote EMT, stemness and metastasis."
  10. Wang YT, (Chen RH)  (2017-08)  Molecular & cellular oncology  4(6), e1364212  "PML degradation fosters an immunosuppressive and pro-metastatic tumor microenvironment."
  11. Wang YT, Chen J, Chang CW, Jen J, Huang TY, Chen CM, Shen R, Liang SY, Cheng IC, Yang SC, Lai WW, Cheng KH, Hsieh TS, Lai MZ, Cheng HC, Wang YC, (Chen RH)  (2017-08)  The Journal of clinical investigation  127(8), 2982-2997  "Ubiquitination of tumor suppressor PML regulates prometastatic and immunosuppressive tumor microenvironment."
  12. Yan X, Zhu Z, Xu S, Yang LN, Liao XH, Zheng M, Yang D, Wang J, Chen D, Wang L, Liu X, Liu J, (Chen RH), Zhou XZ, Lu KP, Liu H  (2017-04)  Scientific reports  7, 45915  "MicroRNA-140-5p inhibits hepatocellular carcinoma by directly targeting the unique isomerase Pin1 to block multiple cancer-driving pathways."
  13. Chou TF, Chuang YT, Hsieh WC, Chang PY, Liu HY, Mo ST, Hsu TS, Miaw SC, (Chen RH), Kimchi A, Lai MZ  (2016-06)  Nature communications  7, 11904  "Tumour suppressor death-associated protein kinase targets cytoplasmic HIF-1alpha for Th17 suppression."
  14. Chen HY, (Chen RH)  (2016-05)  Frontiers in oncology  6, 113  "Cullin 3 Ubiquitin Ligases in Cancer Biology: Functions and Therapeutic Implications."
  15. Liu CC, (Chen RH)  (2016-05)  Autophagy  12(5), 890-891  "KLHL20 links the ubiquitin-proteasome system to autophagy termination."
  16. Chen HY, Liu CC, (Chen RH)  (2016-04)  Cell division  11, 5  "Cul3-KLHL20 ubiquitin ligase: physiological functions, stress responses, and disease implications."
  17. Liu CC, Lin YC, Chen YH, Chen CM, Pang LY, Chen HA, Wu PR, Lin MY, Jiang ST, Tsai TF, (Chen RH)*  (2016-01)  Mol Cell  61(1), 84-97  "Cul3-KLHL20 Ubiquitin Ligase Governs the Turnover of ULK1 and VPS34 Complexes to Control Autophagy Termination."
  18. Chen HY, Hu JY, Chen TH, Lin MY, Lang YD, (Chen RH)*  (2015-10)  ONCOGENE  34(40), 5141-5151  "KLHL39 suppresses colon cancer metastasis by blocking KLHL20-mediated PML and DAPK ubiquitination"
  19. Jiang HC, Hsu JM, Yen CP, Chao CC, (Chen RH), Pan CL  (2015-07)  Proceedings of the National Academy of Sciences of the United States of America  112(28), 8768-8773  "Neural activity and CaMKII protect mitochondria from fragmentation in aging Caenorhabditis elegans neurons."
  20. Tsai TY, Chen TC, Wang IJ, Yeh CY, Su MJ, (Chen RH), Tsai TH, Hu FR  (2015-02)  Investigative ophthalmology & visual science  56(3), 1575-1584  "The effect of resveratrol on protecting corneal epithelial cells from cytotoxicity caused by moxifloxacin and benzalkonium chloride."
  21. Lin YC, Lu LT, Chen HY, Duan X, Lin X, Feng XH, Tang MJ, (Chen RH)   (2014-12)  Cancer research  74, 6935-6946  "SCP phosphatases suppress renal cell carcinoma by stabilizing PML and inhibiting mTOR/HIF signaling."
  22. Tsai, C.-H., H.-C. Cheng, Y.-S. Wang, P. Lin, J. Jen, I.-Y. Kuo, Y.-H. Chang, P.- C. Liao, (R.-H. Chen), W.-C. Yuan, H.-S. Hsu, M.-H. Yang, C.-Y. Wu, and Y.-C. Wang  (2014-09)  Nature Communications  5, 4804  "Small GTPase Rab37 targets tissue inhibitor of metalloproteinase 1 for exocytosis and thus suppresses tumor metastasis"
  23. Yuan WC, Lee YR, Lin SY, Chang LY, Tan YP, Hung CC, Kuo JC, Liu CH, Lin MY, Xu M, Chen ZJ, (Chen RH)  (2014-05)  Molecular cell  54(4), 586-600  "K33-Linked Polyubiquitination of Coronin 7 by Cul3-KLHL20 Ubiquitin E3 Ligase Regulates Protein Trafficking."
  24. Chung KM, Hsu SC, Chu YR, Lin MY, Jiaang WT, (Chen RH), Chen X  (2014-02)  PloS one  9(2), e88772  "Fibroblast activation protein (FAP) is essential for the migration of bone marrow mesenchymal stem cells through RhoA activation."
  25. Lai MZ, (Chen RH)  (2014-02)  Apoptosis : an international journal on programmed cell death  19(2), 357-363  "Regulation of inflammation by DAPK."
  26. Chen HY, Lee YR, (Chen RH)  (2014-02)  Apoptosis : an international journal on programmed cell death  19(2), 364-370  "The functions and regulations of DAPK in cancer metastasis."
  27. Wu, H.-C., Y.-C. Lin, C.-H. Liu, H.-C. Chung. Y.-T. Wang, Y.-W. Lin, H.-I. Ma, P.-H. Tu, S.E. Lawler, and (R.-H. Chen*)  (2014-02)  Nature Communications  5, 3214  "USP11 stabilizes PML to control Notch-induced malignancy in brain tumors"
  28. Chen CH, Chang CC, Lee TH, Luo M, Huang P, Liao PH, Wei S, Li FA, (Chen RH), Zhou XZ, Shih HM, Lu KP  (2013-07)  Cancer research  73(13), 3951-3962  "SENP1 deSUMOylates and regulates Pin1 protein activity and cellular function."
  29. Chang CC, Yang MH, Lin BR, Chen ST, Pan SH, Hsiao M, Lai TC, Lin SK, Jeng YM, Chu CY, (Chen RH), Yang PC, Eugene Chin Y, Kuo ML  (2013-05)  Cell death and differentiation  20(3), 443-455  "CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation."
  30. Tsai PI, Wang M, Kao HH, Cheng YJ, Walker JA, (Chen RH), Chien CT  (2012-11)  The Journal of neuroscience : the official journal of the Society for Neuroscience  32(47), 16971-16981  "Neurofibromin Mediates FAK Signaling in Confining Synapse Growth at Drosophila Neuromuscular Junctions."
  31. Tsai PI, Wang M, Kao HH, Cheng YJ, Lin YJ, (Chen RH), Chien CT  (2012-10)  Proceedings of the National Academy of Sciences of the United States of America  109(43), 17699-17704  "Activity-dependent retrograde laminin A signaling regulates synapse growth at Drosophila neuromuscular junctions."
  32. (Chen RH*), Lee YR, Yuan WC  (2012-08)  Journal of biomedical science  19, 81  "The role of PML ubiquitination in human malignancies."
  33. Chen HY, Lin YM, Chung HC, Lang YD, Lin CJ, Huang J, Wang WC, Lin FM, Chen Z, Huang HD, Shyy JY, Liang JT*, (Chen RH*)  (2012-07)  Cancer research  72(14), 3631-3641  "miR-103/107 promote metastasis of colorectal cancer by targeting the metastasis suppressors DAPK and KLF4."
  34. Huang CY, Chen JY, Wu SC, Tan CH, Tzeng RY, Lu PJ, Wu YF, (Chen RH*), Wu YC*  (2012-05)  PloS one  7(5), e36584  "C. elegans EIF-3.K promotes programmed cell death through CED-3 caspase."
  35. Wu PR, Tsai PI, Chen GC, Chou HJ, Huang YP, Chen YH, Lin MY, Kimchi A, Chien CT, (Chen RH)  (2011-09)  Cell death and differentiation  18(9), 1507-1520  "DAPK activates MARK1/2 to regulate microtubule assembly, neuronal differentiation, and tau toxicity."
  36. Yuan WC, Lee YR, Huang SF, Lin YM, Chen TY, Chung HC, Tsai CH, Chen HY, Chiang CT, Lai CK, Lu LT, Chen CH, Gu DL, Pu YS, Jou YS, Lu KP, Hsiao PW, Shih HM, (Chen RH)  (2011-08)  Cancer cell  20(2), 214-228  "A Cullin3-KLHL20 Ubiquitin Ligase-Dependent Pathway Targets PML to Potentiate HIF-1 Signaling and Prostate Cancer Progression."
  37. Lin MY, Lin YM, Kao TC, Chuang HH, (Chen RH)  (2011-06)  Journal of cell biology  193(6), 985-994  "PDZ-RhoGEF ubiquitination by Cullin3-KLHL20 controls neurotrophin-induced neurite outgrowth."
  38. Lee CW, Leu SJ, Tzeng RY, Wang SF, Tsai SC, Sun KH, (Chen RH), Huang JC  (2011-04)  Virology  413(1), 19-25  "Latent membrane protein 1 of Epstein-Barr virus regulates death-associated protein kinase 1 in lymphoblastoid cell line."
  39. Chang CC, Naik MT, Huang YS, Jeng JC, Liao PH, Kuo HY, Ho CC, Hsieh YL, Lin CH, Huang NJ, Naik NM, Kung CC, Lin SY, (Chen RH), Chang KS, Huang TH, Shih HM  (2011-04)  Molecular cell  42(1), 62-74  "Structural and Functional Roles of Daxx SIM Phosphorylation in SUMO Paralogue-Selective Binding and Apoptosis Modulation."
  40. Chuang, Y.-T., Y.-C. Lin, K. H. Lin, T.-F. Chou, W.-C. Kuo, K.-T. Yang, P.-R. Wu, (R.-H. Chen), A. Kimchi, and M.-Z. Lai  (2011-01)  Blood  117(3), 960-970  "Tumor suppressor death-associated protein kinase is required fro full IL-1β production. "
  41. Lee TH, Chen CH, Suizu F, Huang P, Schiene-Fischer C, Daum S, Zhang YJ, Goate A, (Chen RH), Zhou XZ, Lu KP  (2011)  Molecular cell  42(2), 147-159  "Death-associated protein kinase 1 phosphorylates Pin1 and inhibits its prolyl isomerase activity and cellular function."
  42. Lee Y.-R., W.-C. Yuan, H.-C. Ho, C.-H. Chen, H.-M. Shih, and (R.-H. Chen)  (2010-05)  EMBO J  29(10), 1748-1761  "The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquitination to control interferon responses"
  43. Tsai PI, Kao HH, Grabbe C, Lee YT, Ghose A, Lai TT, Peng KP, Van Vactor D, Palmer RH, (Chen RH), Yeh SR, Chien CT  (2008-10)  Neural development  3, 26  "Fak56 functions downstream of integrin alphaPS3betanu and suppresses MAPK activation in neuromuscular junction growth."
  44. Shen CH, Chen HY, Lin MS, Li FY, Chang CC, Kuo ML, Settleman J, (Chen RH)  (2008)  Cancer research  68(19), 7779-87  "Breast tumor kinase phosphorylates p190RhoGAP to regulate rho and ras and promote breast carcinoma growth, migration, and invasion."
  45. Lin YM, Chen YR, Lin JR, Wang WJ, Inoko A, Inagaki M, Wu YC, (Chen RH)  (2008)  Journal of cell science  121(Pt 14), 2382-93  "eIF3k regulates apoptosis in epithelial cells by releasing caspase 3 from keratin-containing inclusions."
  46. Chuang YT, Fang LW, Lin-Feng MH, (Chen RH), Lai MZ  (2008)  Journal of immunology  180(5), 3238-3249  "The tumor suppressor death-associated protein kinase targets to TCR-stimulated NF-kappa B activation."
  47. W. J. Wang, J. C. Kuo, W. Ku, Y. R. Lee, F. C. Lin, Y. L. Chang, Y. M. Lin, C. H. Chen, Y. P. Huang, M. J. Chiang, S. W. Yeh, P. R. Wu, C. H. Shen, C. T. Wu and (R. H. Chen)  (2007)  Mol Cell  27, 701-716  "The tumor suppressor DAPK is reciprocally regulated by tyrosine kinase Src and phosphatase LAR"
  48. (Chen RH), Wang WJ, Kuo JC  (2006)  Journal of biomedical science  13(2), 193-199  "The tumor suppressor DAP-kinase links cell adhesion and cytoskeleton reorganization to cell death regulation."
  49. J.-C. Kuo, W.-J. Wang, C.-C. Yao, P.-R. Wu and R.-H. Chen  (2006)  J. Cell Biol  172, 619-631  "The tumor suppressor DAPK inhibits cell motility by blocking the integrin-mediated polarity pathway"
  50. C.-H. Chen, W.-J. Wang, J.-C. Kuo, H.-C. Tsai, J.-R. Lin, Z.-F. Chang and R.-H. Chen  (2005)  EMBO J  24, 294-304  "Bi-directional signals transduced by DAPK-ERK interaction promote the apoptotic effect of DAPK"
  51. Chang CC, Lin DY, Fang HI, Chen RH, Shih HM  (2005)  The Journal of biological chemistry  280(11), 10164-10173  "Daxx mediates the small ubiquitin-like modifier-dependent transcriptional repression of Smad4."
  52. Lin SL, Chen RH, Chen YM, Chiang WC, Lai CF, Wu KD, Tsai TJ  (2005)  Journal of the American Society of Nephrology : JASN  16(9), 2702-2713  "Pentoxifylline attenuates tubulointerstitial fibrosis by blocking Smad3/4-activated transcription and profibrogenic effects of connective tissue growth factor."
  53. T.-C. Wang, S.-H. Jee, T.-F. Tsai, Y.-L. Huang, W.-L Tsai and R.-H. Chen  (2005)  British Journal of Dermatology  153, 282-289  "Role of breast tumour kinase in the in vitro differentiation of HaCaT cell"
  54. H.-Y. Chen, C.-H. Shen, Y.-T. Tsai, F.-C. Lin, Y.-P. Huang and R.-H. Chen  (2004)  Mol. Cell Biol  24, 10558-10572  "Brk activates Rac1 and promotes cell migration and invasion by phosphorylating paxillin"
  55. Fang CC, Yen CJ, Tsai TJ, Chen RH, Lee PH, Tomino Y  (2003)  Nephrology  8(3), 142-149  "Antibiotics induce apoptosis of human peritoneal mesothelial cells."
  56. Lin SL, Chen RH, Chen YM, Chiang WC, Tsai TJ, Hsieh BS  (2003)  Molecular pharmacology  64(4), 811-822  "Pentoxifylline inhibits platelet-derived growth factor-stimulated cyclin D1 expression in mesangial cells by blocking Akt membrane translocation."
  57. J.-C. Kuo, J.-R. Lin, J.M. Staddon, H. Hosoya and R.-H. Chen  (2003)  J Cell Sci  116, 4777-4790  "Uncoordinated regulation of stress fibers and focal adhesions by DAP-kinase"
  58. C.-W. Jang, C.-C. Chen, C.-H. Chen, J.-Y. Chen, Y.-H. Su and R.-H. Chen  (2002-01)  Nature Cell Biology  4, 51-58  "TGF-beta induces apoptosis through Smad-mediated expression of the apoptotic DAP-kinase"
  59. W.-J. Wang, J.-C. Kuo, C.-C. Yao and R.-H. Chen  (2002)  J. Cell Biol  159, 169-179  "DAP-kinase induces apoptosis by suppressing integrin activity and disrupting matrix survival signals"
  60. Chunduru S, Kawami H, Gullick R, Monacci WJ, Dougherty G, Cutler ML  (2002)  Journal of neuro-oncology  60(3), 201-211  "Identification of an alternatively spliced RNA for the Ras suppressor RSU-1 in human gliomas."
  61. Y.-T. Tsai, Y.-H. Su, S.-S. Fang, T.-N. Huang, Y. Qiu, Y.-S. Jou, H.-M. Shih, H.-J. Kung and R.-H. Chen  (2000)  Mol. Cell Biol  20, 2043-2054  "Etk, a Btk family tyrosine kinase mediates cellular transformation by linking Src to STAT3 activation"
  62. Liang CL, Tsai CN, Chung PJ, Chen JL, Sun CM, Chen RH, Hong JH, Chang YS  (2000)  Virology  277(1), 184-192  "Transcription of Epstein-Barr virus-encoded nuclear antigen 1 promoter Qp is repressed by transforming growth factor-beta via Smad4 binding element in human BL cells."
  63. Chen RH, Chang MC, Su YH, Tsai YT, Kuo ML  (1999)  The Journal of biological chemistry  274(33), 23013-23019  "Interleukin-6 inhibits transforming growth factor-beta-induced apoptosis through the phosphatidylinositol 3-kinase/Akt and signal transducers and activators of transcription 3 pathways."
  64. Chen RH, Su YH, Chuang RL, Chang TY  (1998)  Oncogene  17(15), 1959-1968  "Suppression of transforming growth factor-beta-induced apoptosis through a phosphatidylinositol 3-kinase/Akt-dependent pathway."
  65. Verlhac MH, Chen RH, Hanachi P, Hershey JW, Derynck R  (1997)  The EMBO journal  16(22), 6812-6822  "Identification of partners of TIF34, a component of the yeast eIF3 complex, required for cell proliferation and translation initiation."
  66. Chen RH, Chang TY  (1997)  Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research  8(7), 821-827  "Involvement of caspase family proteases in transforming growth factor-beta-induced apoptosis."
  67. McGregor WG, Wei D, Chen RH, Maher VM, McCormick JJ  (1997)  Mutation research  376(1-2), 143-152  "Relationship between adduct formation, rates of excision repair and the cytotoxic and mutagenic effects of structurally-related polycyclic aromatic carcinogens."
  68. Lawler S, Feng XH, Chen RH, Maruoka EM, Turck CW, Griswold-Prenner I, Derynck R  (1997)  The Journal of biological chemistry  272(23), 14850-14859  "The type II transforming growth factor-beta receptor autophosphorylates not only on serine and threonine but also on tyrosine residues."
  69. Chen RH, Miettinen PJ, Maruoka EM, Choy L, Derynck R  (1995)  Nature  377(6549), 548-552  "A WD-domain protein that is associated with and phosphorylated by the type II TGF-beta receptor."
  70. McGregor WG, Mah MC, Chen RW, Maher VM, McCormick JJ  (1995)  The Journal of biological chemistry  270(45), 27222-27227  "Lack of correlation between degree of interference with transcription and rate of strand specific repair in the HPRT gene of diploid human fibroblasts."
  71. Chen RH, Moses HL, Maruoka EM, Derynck R, Kawabata M  (1995)  The Journal of biological chemistry  270(20), 12235-12241  "Phosphorylation-dependent interaction of the cytoplasmic domains of the type I and type II transforming growth factor-beta receptors."
  72. Chen RH, Derynck R  (1994)  The Journal of biological chemistry  269(36), 22868-22874  "Homomeric interactions between type II transforming growth factor-beta receptors."
  73. Ebner R, Chen RH, Shum L, Lawler S, Zioncheck TF, Lee A, Lopez AR, Derynck R  (1993)  Science  260(5112), 1344-1348  "Cloning of a type I TGF-beta receptor and its effect on TGF-beta binding to the type II receptor."
  74. Ebner R, Chen RH, Lawler S, Zioncheck T, Derynck R  (1993)  Science  262(5135), 900-902  "Determination of type I receptor specificity by the type II receptors for TGF-beta or activin."
  75. Chen RH, Ebner R, Derynck R  (1993)  Science  260(5112), 1335-1338  "Inactivation of the type II receptor reveals two receptor pathways for the diverse TGF-beta activities."
  76. Chen RH, Maher VM, Brouwer J, van de Putte P, McCormick JJ  (1992)  Proceedings of the National Academy of Sciences of the United States of America  89(12), 5413-5417  "Preferential repair and strand-specific repair of benzo[a]pyrene diol epoxide adducts in the HPRT gene of diploid human fibroblasts."
  77. McGregor WG, Chen RH, Lukash L, Maher VM, McCormick JJ  (1991)  Molecular and cellular biology  11(4), 1927-1934  "Cell cycle-dependent strand bias for UV-induced mutations in the transcribed strand of excision repair-proficient human fibroblasts but not in repair-deficient cells."
  78. Yang JL, Chen RH, Maher VM, McCormick JJ  (1991)  Carcinogenesis  12(1), 71-75  "Kinds and location of mutations induced by (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene in the coding region of the hypoxanthine (guanine) phosphoribosyltransferase gene in diploid human fibroblasts."
  79. Chen RH, Maher VM, McCormick JJ  (1991)  Cancer research  51(10), 2587-2592  "Lack of a cell cycle-dependent strand bias for mutations induced in the HPRT gene by (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene in excision repair-deficient human cells."
  80. Chen RH, Maher VM, McCormick JJ  (1990)  Proceedings of the National Academy of Sciences of the United States of America  87(21), 8680-8684  "Effect of excision repair by diploid human fibroblasts on the kinds and locations of mutations induced by (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene in the coding region of the HPRT gene."
  1. The roles of cullin-RING family ubiquitin ligases in human cancers

    The cullin-RING (CRL) superfamily consists of the largest family of ubiquitin ligases in eukaryotes. Substrate recognition of this family of ubiquitin ligases is achieved by a large set of substrate receptors. A number of substrate receptors are mutated or deregulated in cancers, such as VHL, Fbw7 and Keap1. My laboratory recently identified KLHL20 as a substrate receptor of Cullin3 family ligase. KLHL20 is induced by tumor microenvironment (i.e., hypoxia) and is responsible for ubiquitin-mediated degradation of multiple tumor suppressors, such as DAPK and PML. In addition to KLHL20, we are interested in several other substrate receptors of CRL family ligases that are deregulated in human cancers. Identification of their substrates and determination of functions of these ubiquitination events in tumor formation, progression, and/or tumor stem cell maintenance are current focuses in the lab.

  2. The roles of ubiquitination in autophagy regulation

    Autophagy is an evolutionarily conserved catabolic pathway and participates in diverse physiological processes, such as adaptation to starvation, cell differentiation and development, degradation of aberrant structures, turnover of superfluous or damaged organelles, tumor suppression, innate and adaptive immunity, life span extension and cell death. The role of protein posttranslational modifications in autophagy regulation has emerged. My laboratory recently identified KLHL20 as a critical regulator of autophagy. Current studies are focused on KLHL20-regulated ubiquitination event in autophagy regulation and the physiological significance of this ubiquitination event using cell-based approaches and animal models. In addition, we have employed system biology approaches to identify other ubiquitination events important in autophagy regulation.

Positions Held
  • 2012 – present   Distinguished Research Fellow, Institute of Biological Chemistry, Academia Sinica
  • 2011 – 2014   Deputy Director, Institute of Biological Chemistry, Academia Sinica
  • 2006 – 2012   Research Fellow, Institute of Biological Chemistry, Academia Sinica
  • 2003 – 2006   Professor, Institute of Molecular Medicine, College of Medicine, National Taiwan University
  • 1996 – 2003   Associate Professor, Institute of Molecular Medicine, College of Medicine, National Taiwan University
  • 1995 – 1996   Assistant Biochemist, University of California at San Francisco
  • 1992 – 1995   Postdoctoral Fellow, University of California at San Francisco
Degrees
  • 1987 – 1991   Ph.D, Biochemistry, Michigan State University
  • 1983 – 1985   M.S., Biochemistry, National Taiwan University
  • 1979 – 1983   B.S., Agricultural Chemistry, National Taiwan University
Wang YT, Chen J, Chang CW, Jen J, Huang TY, Chen CM, Shen R, Liang SY, Cheng IC, Yang SC, Lai WW, Cheng KH, Hsieh TS, Lai MZ, Cheng HC, Wang YC, Chen RH
J Clin Invest (2017)
Liu, C.-C., Y.-C. Lin, Y.-H. Chen, C.-M. Chen, L.-Y. Pang, H.-A. Chen, P.-R. Wu, M.-Y. Lin, S.-T Jiang, T.-F. Tai, and R.-H. Chen
Mol Cell (2016)
Yuan, W-C, Y-R Lee, S-Y Lin, J-C Kuo, YP Tan, L-Y Chang, C-H Liu, M-Y Lin, M Xu, Z J Chen, and R-H Chen
Mol Cell (2014)
Lin YC, Lu LT, Chen HY, Duan X, Lin X, Feng XH, Tang MJ, Chen RH
Cancer Research (2014)
Wu, H-C, Y-C Lin, C-H Liu, H-C Chung,Y-T Wang, Y-W Lin, H-I Ma, P-H Tu, SE Lawler, and R-H Chen
Nature Commun (2014)
Chen HY, Lin YM, Chung HC, Lang YD, Lin CJ, Huang J, Wang WC, Lin FM, Chen Z, Huang HD, Shyy JY, Liang JT, Chen RH
Cancer research (2012)
Yuan WC, Lee YR, Huang SF, Lin YM, Chen TY, Chung HC, Tsai CH, Chen HY, Chiang CT, Lai CK, Lu LT, Chen CH, Gu DL, Pu YS, Jou YS, Lu KP, Hsiao PW, Shih HM, Chen RH
Cancer cell (2011)
Wu PR, Tsai PI, Chen GC, Chou HJ, Huang YP, Chen YH, Lin MY, Kimchi A, Chien CT, Chen RH
Cell death and differentiation (2011)
Lin MY, Lin YM, Kao TC, Chuang HH, Chen RH
Journal of cell biology (2011)
Lee Y.-R., W.-C. Yuan, H.-C. Ho, C.-H. Chen, H.-M. Shih, and R.-H. Chen
EMBO J (2010)
  1. Lu G, Yi J, Gubas A, Wang YT, Wu Y, Ren Y, Wu M, Shi Y, Ouyang C, Tan HWS, Wang T, Wang L, Yang ND, Deng S, Xia D, (Chen RH), Tooze SA, Shen HM*  (2019-11)  Autophagy  15(11), 1917-1934  "Suppression of autophagy during mitosis via CUL4-RING ubiquitin ligases-mediated WIPI2 polyubiquitination and proteasomal degradation."
  2. (Chen RH), Chen YH, Huang TY  (2019-10)  Journal of biomedical science  26(1), 80  "Ubiquitin-mediated regulation of autophagy."
  3. Chen FY, Huang MY, Lin YM, Ho CH, Lin SY, Chen HY, Hung MC, (Chen RH)  (2019-09)  Journal of Cell Biology  218(9), 3002-3018  "BIK ubiquitination by the E3 ligase Cul5-ASB11 determines cell fate during cellular stress."
  4. Tan BS, Yang MC, Singh S, Chou YC, Chen HY, Wang MY, Wang YC, (Chen RH*)  (2019-07)  ONCOGENE  38(28), 5612–5626  "LncRNA NORAD is repressed by the YAP pathway and suppresses lung and breast cancer metastasis by sequestering S100P."
  5. Chen HY, Lang YD, Lin HN, Liu YR, Liao CC, Nana AW, Yen Y, (Chen RH)  (2019-07)  Scientific reports  9(1), 9687  "miR-103/107 prolong Wnt/beta-catenin signaling and colorectal cancer stemness by targeting Axin2."
  6. Huang HH, Chen FY, Chou WC, Hou HA, Ko BS, Lin CT, Tang JL, Li CC, Yao M, Tsay W, Hsu SC, Wu SJ, Chen CY, Huang SY, Tseng MH, Tien HF, (Chen RH)  (2019-06)  BMC cancer  19(1), 617  "Long non-coding RNA HOXB-AS3 promotes myeloid cell proliferation and its higher expression is an adverse prognostic marker in patients with acute myeloid leukemia and myelodysplastic syndrome."
  7. Lee YR, Chen M, Lee JD, Zhang J, Lin SY, Fu TM, Chen H, Ishikawa T, Chiang SY, Katon J, Zhang Y, Shulga YV, Bester AC, Fung J, Monteleone E, Wan L, Shen C, Hsu CH, Papa A, Clohessy JG, Teruya-Feldstein J, Jain S, Wu H, Matesic L, (Chen RH), Wei W, Pandolfi PP*  (2019-05)  SCIENCE  364(6441), eaau0159  "Reactivation of PTEN tumor suppressor for cancer treatment through inhibition of a MYC-WWP1 inhibitory pathway."
  8. Liang KH, Tso HC, Hung SH, Kuan II, Lai JK, Ke FY, Chuang YT, Liu IJ, Wang YP, (Chen RH), Wu HC  (2018-10)  Cancer letters  433, 165-175  "Extracellular domain of EpCAM enhances tumor progression through EGFR signaling in colon cancer cells."
  9. Yeh HW, Hsu EC, Lee SS, Lang YD, Lin YC, Chang CY, Lee SY, Gu DL, Shih JH, Ho CM, Chen CF, Chen CT, Tu PH, Cheng CF, (Chen RH), Yang RB, Jou YS  (2018-04)  Nature cell biology  20(4), 479-491  "PSPC1 mediates TGF-beta1 autocrine signalling and Smad2/3 target switching to promote EMT, stemness and metastasis."
  10. Wang YT, (Chen RH)  (2017-08)  Molecular & cellular oncology  4(6), e1364212  "PML degradation fosters an immunosuppressive and pro-metastatic tumor microenvironment."
  11. Wang YT, Chen J, Chang CW, Jen J, Huang TY, Chen CM, Shen R, Liang SY, Cheng IC, Yang SC, Lai WW, Cheng KH, Hsieh TS, Lai MZ, Cheng HC, Wang YC, (Chen RH)  (2017-08)  The Journal of clinical investigation  127(8), 2982-2997  "Ubiquitination of tumor suppressor PML regulates prometastatic and immunosuppressive tumor microenvironment."
  12. Yan X, Zhu Z, Xu S, Yang LN, Liao XH, Zheng M, Yang D, Wang J, Chen D, Wang L, Liu X, Liu J, (Chen RH), Zhou XZ, Lu KP, Liu H  (2017-04)  Scientific reports  7, 45915  "MicroRNA-140-5p inhibits hepatocellular carcinoma by directly targeting the unique isomerase Pin1 to block multiple cancer-driving pathways."
  13. Chou TF, Chuang YT, Hsieh WC, Chang PY, Liu HY, Mo ST, Hsu TS, Miaw SC, (Chen RH), Kimchi A, Lai MZ  (2016-06)  Nature communications  7, 11904  "Tumour suppressor death-associated protein kinase targets cytoplasmic HIF-1alpha for Th17 suppression."
  14. Chen HY, (Chen RH)  (2016-05)  Frontiers in oncology  6, 113  "Cullin 3 Ubiquitin Ligases in Cancer Biology: Functions and Therapeutic Implications."
  15. Liu CC, (Chen RH)  (2016-05)  Autophagy  12(5), 890-891  "KLHL20 links the ubiquitin-proteasome system to autophagy termination."
  16. Chen HY, Liu CC, (Chen RH)  (2016-04)  Cell division  11, 5  "Cul3-KLHL20 ubiquitin ligase: physiological functions, stress responses, and disease implications."
  17. Liu CC, Lin YC, Chen YH, Chen CM, Pang LY, Chen HA, Wu PR, Lin MY, Jiang ST, Tsai TF, (Chen RH)*  (2016-01)  Mol Cell  61(1), 84-97  "Cul3-KLHL20 Ubiquitin Ligase Governs the Turnover of ULK1 and VPS34 Complexes to Control Autophagy Termination."
  18. Chen HY, Hu JY, Chen TH, Lin MY, Lang YD, (Chen RH)*  (2015-10)  ONCOGENE  34(40), 5141-5151  "KLHL39 suppresses colon cancer metastasis by blocking KLHL20-mediated PML and DAPK ubiquitination"
  19. Jiang HC, Hsu JM, Yen CP, Chao CC, (Chen RH), Pan CL  (2015-07)  Proceedings of the National Academy of Sciences of the United States of America  112(28), 8768-8773  "Neural activity and CaMKII protect mitochondria from fragmentation in aging Caenorhabditis elegans neurons."
  20. Tsai TY, Chen TC, Wang IJ, Yeh CY, Su MJ, (Chen RH), Tsai TH, Hu FR  (2015-02)  Investigative ophthalmology & visual science  56(3), 1575-1584  "The effect of resveratrol on protecting corneal epithelial cells from cytotoxicity caused by moxifloxacin and benzalkonium chloride."
  21. Lin YC, Lu LT, Chen HY, Duan X, Lin X, Feng XH, Tang MJ, (Chen RH)   (2014-12)  Cancer research  74, 6935-6946  "SCP phosphatases suppress renal cell carcinoma by stabilizing PML and inhibiting mTOR/HIF signaling."
  22. Tsai, C.-H., H.-C. Cheng, Y.-S. Wang, P. Lin, J. Jen, I.-Y. Kuo, Y.-H. Chang, P.- C. Liao, (R.-H. Chen), W.-C. Yuan, H.-S. Hsu, M.-H. Yang, C.-Y. Wu, and Y.-C. Wang  (2014-09)  Nature Communications  5, 4804  "Small GTPase Rab37 targets tissue inhibitor of metalloproteinase 1 for exocytosis and thus suppresses tumor metastasis"
  23. Yuan WC, Lee YR, Lin SY, Chang LY, Tan YP, Hung CC, Kuo JC, Liu CH, Lin MY, Xu M, Chen ZJ, (Chen RH)  (2014-05)  Molecular cell  54(4), 586-600  "K33-Linked Polyubiquitination of Coronin 7 by Cul3-KLHL20 Ubiquitin E3 Ligase Regulates Protein Trafficking."
  24. Chung KM, Hsu SC, Chu YR, Lin MY, Jiaang WT, (Chen RH), Chen X  (2014-02)  PloS one  9(2), e88772  "Fibroblast activation protein (FAP) is essential for the migration of bone marrow mesenchymal stem cells through RhoA activation."
  25. Lai MZ, (Chen RH)  (2014-02)  Apoptosis : an international journal on programmed cell death  19(2), 357-363  "Regulation of inflammation by DAPK."
  26. Chen HY, Lee YR, (Chen RH)  (2014-02)  Apoptosis : an international journal on programmed cell death  19(2), 364-370  "The functions and regulations of DAPK in cancer metastasis."
  27. Wu, H.-C., Y.-C. Lin, C.-H. Liu, H.-C. Chung. Y.-T. Wang, Y.-W. Lin, H.-I. Ma, P.-H. Tu, S.E. Lawler, and (R.-H. Chen*)  (2014-02)  Nature Communications  5, 3214  "USP11 stabilizes PML to control Notch-induced malignancy in brain tumors"
  28. Chen CH, Chang CC, Lee TH, Luo M, Huang P, Liao PH, Wei S, Li FA, (Chen RH), Zhou XZ, Shih HM, Lu KP  (2013-07)  Cancer research  73(13), 3951-3962  "SENP1 deSUMOylates and regulates Pin1 protein activity and cellular function."
  29. Chang CC, Yang MH, Lin BR, Chen ST, Pan SH, Hsiao M, Lai TC, Lin SK, Jeng YM, Chu CY, (Chen RH), Yang PC, Eugene Chin Y, Kuo ML  (2013-05)  Cell death and differentiation  20(3), 443-455  "CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation."
  30. Tsai PI, Wang M, Kao HH, Cheng YJ, Walker JA, (Chen RH), Chien CT  (2012-11)  The Journal of neuroscience : the official journal of the Society for Neuroscience  32(47), 16971-16981  "Neurofibromin Mediates FAK Signaling in Confining Synapse Growth at Drosophila Neuromuscular Junctions."
  31. Tsai PI, Wang M, Kao HH, Cheng YJ, Lin YJ, (Chen RH), Chien CT  (2012-10)  Proceedings of the National Academy of Sciences of the United States of America  109(43), 17699-17704  "Activity-dependent retrograde laminin A signaling regulates synapse growth at Drosophila neuromuscular junctions."
  32. (Chen RH*), Lee YR, Yuan WC  (2012-08)  Journal of biomedical science  19, 81  "The role of PML ubiquitination in human malignancies."
  33. Chen HY, Lin YM, Chung HC, Lang YD, Lin CJ, Huang J, Wang WC, Lin FM, Chen Z, Huang HD, Shyy JY, Liang JT*, (Chen RH*)  (2012-07)  Cancer research  72(14), 3631-3641  "miR-103/107 promote metastasis of colorectal cancer by targeting the metastasis suppressors DAPK and KLF4."
  34. Huang CY, Chen JY, Wu SC, Tan CH, Tzeng RY, Lu PJ, Wu YF, (Chen RH*), Wu YC*  (2012-05)  PloS one  7(5), e36584  "C. elegans EIF-3.K promotes programmed cell death through CED-3 caspase."
  35. Wu PR, Tsai PI, Chen GC, Chou HJ, Huang YP, Chen YH, Lin MY, Kimchi A, Chien CT, (Chen RH)  (2011-09)  Cell death and differentiation  18(9), 1507-1520  "DAPK activates MARK1/2 to regulate microtubule assembly, neuronal differentiation, and tau toxicity."
  36. Yuan WC, Lee YR, Huang SF, Lin YM, Chen TY, Chung HC, Tsai CH, Chen HY, Chiang CT, Lai CK, Lu LT, Chen CH, Gu DL, Pu YS, Jou YS, Lu KP, Hsiao PW, Shih HM, (Chen RH)  (2011-08)  Cancer cell  20(2), 214-228  "A Cullin3-KLHL20 Ubiquitin Ligase-Dependent Pathway Targets PML to Potentiate HIF-1 Signaling and Prostate Cancer Progression."
  37. Lin MY, Lin YM, Kao TC, Chuang HH, (Chen RH)  (2011-06)  Journal of cell biology  193(6), 985-994  "PDZ-RhoGEF ubiquitination by Cullin3-KLHL20 controls neurotrophin-induced neurite outgrowth."
  38. Lee CW, Leu SJ, Tzeng RY, Wang SF, Tsai SC, Sun KH, (Chen RH), Huang JC  (2011-04)  Virology  413(1), 19-25  "Latent membrane protein 1 of Epstein-Barr virus regulates death-associated protein kinase 1 in lymphoblastoid cell line."
  39. Chang CC, Naik MT, Huang YS, Jeng JC, Liao PH, Kuo HY, Ho CC, Hsieh YL, Lin CH, Huang NJ, Naik NM, Kung CC, Lin SY, (Chen RH), Chang KS, Huang TH, Shih HM  (2011-04)  Molecular cell  42(1), 62-74  "Structural and Functional Roles of Daxx SIM Phosphorylation in SUMO Paralogue-Selective Binding and Apoptosis Modulation."
  40. Chuang, Y.-T., Y.-C. Lin, K. H. Lin, T.-F. Chou, W.-C. Kuo, K.-T. Yang, P.-R. Wu, (R.-H. Chen), A. Kimchi, and M.-Z. Lai  (2011-01)  Blood  117(3), 960-970  "Tumor suppressor death-associated protein kinase is required fro full IL-1β production. "
  41. Lee TH, Chen CH, Suizu F, Huang P, Schiene-Fischer C, Daum S, Zhang YJ, Goate A, (Chen RH), Zhou XZ, Lu KP  (2011)  Molecular cell  42(2), 147-159  "Death-associated protein kinase 1 phosphorylates Pin1 and inhibits its prolyl isomerase activity and cellular function."
  42. Lee Y.-R., W.-C. Yuan, H.-C. Ho, C.-H. Chen, H.-M. Shih, and (R.-H. Chen)  (2010-05)  EMBO J  29(10), 1748-1761  "The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquitination to control interferon responses"
  43. Tsai PI, Kao HH, Grabbe C, Lee YT, Ghose A, Lai TT, Peng KP, Van Vactor D, Palmer RH, (Chen RH), Yeh SR, Chien CT  (2008-10)  Neural development  3, 26  "Fak56 functions downstream of integrin alphaPS3betanu and suppresses MAPK activation in neuromuscular junction growth."
  44. Shen CH, Chen HY, Lin MS, Li FY, Chang CC, Kuo ML, Settleman J, (Chen RH)  (2008)  Cancer research  68(19), 7779-87  "Breast tumor kinase phosphorylates p190RhoGAP to regulate rho and ras and promote breast carcinoma growth, migration, and invasion."
  45. Lin YM, Chen YR, Lin JR, Wang WJ, Inoko A, Inagaki M, Wu YC, (Chen RH)  (2008)  Journal of cell science  121(Pt 14), 2382-93  "eIF3k regulates apoptosis in epithelial cells by releasing caspase 3 from keratin-containing inclusions."
  46. Chuang YT, Fang LW, Lin-Feng MH, (Chen RH), Lai MZ  (2008)  Journal of immunology  180(5), 3238-3249  "The tumor suppressor death-associated protein kinase targets to TCR-stimulated NF-kappa B activation."
  47. W. J. Wang, J. C. Kuo, W. Ku, Y. R. Lee, F. C. Lin, Y. L. Chang, Y. M. Lin, C. H. Chen, Y. P. Huang, M. J. Chiang, S. W. Yeh, P. R. Wu, C. H. Shen, C. T. Wu and (R. H. Chen)  (2007)  Mol Cell  27, 701-716  "The tumor suppressor DAPK is reciprocally regulated by tyrosine kinase Src and phosphatase LAR"
  48. (Chen RH), Wang WJ, Kuo JC  (2006)  Journal of biomedical science  13(2), 193-199  "The tumor suppressor DAP-kinase links cell adhesion and cytoskeleton reorganization to cell death regulation."
  49. J.-C. Kuo, W.-J. Wang, C.-C. Yao, P.-R. Wu and R.-H. Chen  (2006)  J. Cell Biol  172, 619-631  "The tumor suppressor DAPK inhibits cell motility by blocking the integrin-mediated polarity pathway"
  50. C.-H. Chen, W.-J. Wang, J.-C. Kuo, H.-C. Tsai, J.-R. Lin, Z.-F. Chang and R.-H. Chen  (2005)  EMBO J  24, 294-304  "Bi-directional signals transduced by DAPK-ERK interaction promote the apoptotic effect of DAPK"
  51. Chang CC, Lin DY, Fang HI, Chen RH, Shih HM  (2005)  The Journal of biological chemistry  280(11), 10164-10173  "Daxx mediates the small ubiquitin-like modifier-dependent transcriptional repression of Smad4."
  52. Lin SL, Chen RH, Chen YM, Chiang WC, Lai CF, Wu KD, Tsai TJ  (2005)  Journal of the American Society of Nephrology : JASN  16(9), 2702-2713  "Pentoxifylline attenuates tubulointerstitial fibrosis by blocking Smad3/4-activated transcription and profibrogenic effects of connective tissue growth factor."
  53. T.-C. Wang, S.-H. Jee, T.-F. Tsai, Y.-L. Huang, W.-L Tsai and R.-H. Chen  (2005)  British Journal of Dermatology  153, 282-289  "Role of breast tumour kinase in the in vitro differentiation of HaCaT cell"
  54. H.-Y. Chen, C.-H. Shen, Y.-T. Tsai, F.-C. Lin, Y.-P. Huang and R.-H. Chen  (2004)  Mol. Cell Biol  24, 10558-10572  "Brk activates Rac1 and promotes cell migration and invasion by phosphorylating paxillin"
  55. Fang CC, Yen CJ, Tsai TJ, Chen RH, Lee PH, Tomino Y  (2003)  Nephrology  8(3), 142-149  "Antibiotics induce apoptosis of human peritoneal mesothelial cells."
  56. Lin SL, Chen RH, Chen YM, Chiang WC, Tsai TJ, Hsieh BS  (2003)  Molecular pharmacology  64(4), 811-822  "Pentoxifylline inhibits platelet-derived growth factor-stimulated cyclin D1 expression in mesangial cells by blocking Akt membrane translocation."
  57. J.-C. Kuo, J.-R. Lin, J.M. Staddon, H. Hosoya and R.-H. Chen  (2003)  J Cell Sci  116, 4777-4790  "Uncoordinated regulation of stress fibers and focal adhesions by DAP-kinase"
  58. C.-W. Jang, C.-C. Chen, C.-H. Chen, J.-Y. Chen, Y.-H. Su and R.-H. Chen  (2002-01)  Nature Cell Biology  4, 51-58  "TGF-beta induces apoptosis through Smad-mediated expression of the apoptotic DAP-kinase"
  59. W.-J. Wang, J.-C. Kuo, C.-C. Yao and R.-H. Chen  (2002)  J. Cell Biol  159, 169-179  "DAP-kinase induces apoptosis by suppressing integrin activity and disrupting matrix survival signals"
  60. Chunduru S, Kawami H, Gullick R, Monacci WJ, Dougherty G, Cutler ML  (2002)  Journal of neuro-oncology  60(3), 201-211  "Identification of an alternatively spliced RNA for the Ras suppressor RSU-1 in human gliomas."
  61. Y.-T. Tsai, Y.-H. Su, S.-S. Fang, T.-N. Huang, Y. Qiu, Y.-S. Jou, H.-M. Shih, H.-J. Kung and R.-H. Chen  (2000)  Mol. Cell Biol  20, 2043-2054  "Etk, a Btk family tyrosine kinase mediates cellular transformation by linking Src to STAT3 activation"
  62. Liang CL, Tsai CN, Chung PJ, Chen JL, Sun CM, Chen RH, Hong JH, Chang YS  (2000)  Virology  277(1), 184-192  "Transcription of Epstein-Barr virus-encoded nuclear antigen 1 promoter Qp is repressed by transforming growth factor-beta via Smad4 binding element in human BL cells."
  63. Chen RH, Chang MC, Su YH, Tsai YT, Kuo ML  (1999)  The Journal of biological chemistry  274(33), 23013-23019  "Interleukin-6 inhibits transforming growth factor-beta-induced apoptosis through the phosphatidylinositol 3-kinase/Akt and signal transducers and activators of transcription 3 pathways."
  64. Chen RH, Su YH, Chuang RL, Chang TY  (1998)  Oncogene  17(15), 1959-1968  "Suppression of transforming growth factor-beta-induced apoptosis through a phosphatidylinositol 3-kinase/Akt-dependent pathway."
  65. Verlhac MH, Chen RH, Hanachi P, Hershey JW, Derynck R  (1997)  The EMBO journal  16(22), 6812-6822  "Identification of partners of TIF34, a component of the yeast eIF3 complex, required for cell proliferation and translation initiation."
  66. Chen RH, Chang TY  (1997)  Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research  8(7), 821-827  "Involvement of caspase family proteases in transforming growth factor-beta-induced apoptosis."
  67. McGregor WG, Wei D, Chen RH, Maher VM, McCormick JJ  (1997)  Mutation research  376(1-2), 143-152  "Relationship between adduct formation, rates of excision repair and the cytotoxic and mutagenic effects of structurally-related polycyclic aromatic carcinogens."
  68. Lawler S, Feng XH, Chen RH, Maruoka EM, Turck CW, Griswold-Prenner I, Derynck R  (1997)  The Journal of biological chemistry  272(23), 14850-14859  "The type II transforming growth factor-beta receptor autophosphorylates not only on serine and threonine but also on tyrosine residues."
  69. Chen RH, Miettinen PJ, Maruoka EM, Choy L, Derynck R  (1995)  Nature  377(6549), 548-552  "A WD-domain protein that is associated with and phosphorylated by the type II TGF-beta receptor."
  70. McGregor WG, Mah MC, Chen RW, Maher VM, McCormick JJ  (1995)  The Journal of biological chemistry  270(45), 27222-27227  "Lack of correlation between degree of interference with transcription and rate of strand specific repair in the HPRT gene of diploid human fibroblasts."
  71. Chen RH, Moses HL, Maruoka EM, Derynck R, Kawabata M  (1995)  The Journal of biological chemistry  270(20), 12235-12241  "Phosphorylation-dependent interaction of the cytoplasmic domains of the type I and type II transforming growth factor-beta receptors."
  72. Chen RH, Derynck R  (1994)  The Journal of biological chemistry  269(36), 22868-22874  "Homomeric interactions between type II transforming growth factor-beta receptors."
  73. Ebner R, Chen RH, Shum L, Lawler S, Zioncheck TF, Lee A, Lopez AR, Derynck R  (1993)  Science  260(5112), 1344-1348  "Cloning of a type I TGF-beta receptor and its effect on TGF-beta binding to the type II receptor."
  74. Ebner R, Chen RH, Lawler S, Zioncheck T, Derynck R  (1993)  Science  262(5135), 900-902  "Determination of type I receptor specificity by the type II receptors for TGF-beta or activin."
  75. Chen RH, Ebner R, Derynck R  (1993)  Science  260(5112), 1335-1338  "Inactivation of the type II receptor reveals two receptor pathways for the diverse TGF-beta activities."
  76. Chen RH, Maher VM, Brouwer J, van de Putte P, McCormick JJ  (1992)  Proceedings of the National Academy of Sciences of the United States of America  89(12), 5413-5417  "Preferential repair and strand-specific repair of benzo[a]pyrene diol epoxide adducts in the HPRT gene of diploid human fibroblasts."
  77. McGregor WG, Chen RH, Lukash L, Maher VM, McCormick JJ  (1991)  Molecular and cellular biology  11(4), 1927-1934  "Cell cycle-dependent strand bias for UV-induced mutations in the transcribed strand of excision repair-proficient human fibroblasts but not in repair-deficient cells."
  78. Yang JL, Chen RH, Maher VM, McCormick JJ  (1991)  Carcinogenesis  12(1), 71-75  "Kinds and location of mutations induced by (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene in the coding region of the hypoxanthine (guanine) phosphoribosyltransferase gene in diploid human fibroblasts."
  79. Chen RH, Maher VM, McCormick JJ  (1991)  Cancer research  51(10), 2587-2592  "Lack of a cell cycle-dependent strand bias for mutations induced in the HPRT gene by (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene in excision repair-deficient human cells."
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