Programme

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SPEAKERS

Ruey-Hwa Chen

AFFILIATION:

Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan

POSITION TITLE:

Distinguished Research Fellow

EDUCATION/TRAINING:

National Taiwan University B.S. Agricultural Chemistry 1979-1983

National Taiwan University M.S. Biochemical Science 1983-1985

Michigan State University Ph.D. Biochemistry 1987-1991

 

HONORS:

Outstanding Student, National Taiwan University, 1982

National Defense & Technology Scholarship Award, Taiwan, 1983-1985

Phi Beta Delta - Honor Society for International Scholars, 1989

Outstanding Graduate Student Award, Dept of Biochemistry, Michigan State University, 1991

Postdoctoral Fellowship Award, Tobacco-Related Diseases Research Program, 1993-1995

Special Fellow Award, Leukemia Society of America, 1995-1996

Outstanding Paper Award, Juei-Low Sung’s Academic Foundation, 1999

Outstanding Young Investigator Award, Academia Sinica, 2001

Frontier of Research Grant Award, National Science Council, 1998-2003

Frontier of Research Grant Award, National Science Council, 2004-2009

Outstanding Research Award, National Science Council, 1998

Outstanding Research Award, National Science Council, 2000

Outstanding Research Award, National Science Council, 2002

Teaching Award, College of Medicine, National Taiwan University, 2004 

Teaching Award, College of Medicine, National Taiwan University, 2006

Academia Sinica Investigator Award, Academia Sinica, 2008-2012, 2013-2017, 2018-2022

Frontier of Research Grant Award, National Science Council, 2009-2014

Frontier of Research Grant Award, National Science Council, 2015-2019

Outstanding Scholar Research Grant, National Science Council, 2009-2012

Honorary Member, TienTe Lee Award Laureate Club, 2011

Merit Research Award, National Science Council, 2012-2015

The 9th Outstanding Award, TienTe Lee Biomedical Foundation, 2013

TBF (Taiwan Biotechnology Foundation) Chair in Biotechnology, 2014

The 59th Academic Award, The Ministry of Education, 2015

Merit MOST Research Fellow Award, 2016

Taiwan Outstanding Women in Science, Wu Chien-Shiung Education Foundation, 2016 

Academic Summit Grant, MOST, 2019-2024

TWAS Award in Biology, 2020

 

RESEARCH INTERESTS:

  1. Protein degradation and exosomal secretion in controlling cancer cell signaling and tumor immune microenvironment

    We are interested in how cells ensure a balance between lysosomal degradation and exosomal secretion, how protein ubiquitination impacts on this balance, and how cancer cells perturb this balance to potentiate tumor malignant phenotypes and immunosuppressive tumor microenvironment. These regulatory mechanisms will be exploited for designing new anti-cancer strategies.

  2. Targeting proteasomal and lysosomal degradation of oncoproteins for anti-cancer therapy

    “Degradation” has emerged as a new concept of anti-cancer strategy and offers several advantages over the traditional “inhibition” strategy. We are interested in uncovering new proteasomal and lysosomal degradation pathways and/or strategies for several major oncoproteins.

  3. Regulation of cancer metabolism by biomolecular condensates

    Biomolecular condensates are intracellular membraneless compartments assembled through liquid-liquid phase separation arising from weak interactions among proteins and nucleic acids. Dysregulation of biomolecular condensates has been linked to disease states such as neurodegeneration and cancer. We are interested in the assembly/disassembly mechanisms and compositions of the biomolecular condensate that impacts on cancer metabolism.

PUBLICATIONS:

1)  Chen, R.-H., V.M. Maher, and J.J. McCormick (1990) Effect of excision repair by diploid human fibroblasts on the kinds and locations of mutations induced by (+)-7β, 8α-dihydroxy-9α, 10α-epoxy-7, 8, 9, 10 -tetrahydrobenzo[a]pyrene in the coding region of the HPRT gene. Proc. Natl. Acad. Sci. (USA), 87: 8680-8685.

 

2)  Yang, J.-L., R.-H. Chen, V.M. Maher, and J.J. McCormick (1991) Kinds and locations of mutations induced by (+)-7β, 8α-dihydroxy-9α, 10α-epoxy-7, 8, 9, 10 -tetrahydrobenzo[a]pyrene in the coding region of the hypoxanthine (guanine) phosphoribosyltransferase gene in diploid human fibroblasts. Carcinogenesis, 12: 71-75.

 

3)  McGregor, W.G., R.-H. Chen, L. Lukash, V.M. Maher, and J.J. McCormick (1991) 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. Mol. Cell. Biol., 11: 1927-1934.

 

4)  Chen, R.-H., V.M. Maher, and J.J. McCormick (1991) Lack of a cell cycle-dependent strand bias for mutations induced in the HPRT gene by (+)-7β, 8α-dihydroxy-9α, 10α-epoxy-7, 8, 9, 10 -tetrahydrobenzo[a] pyrene in excision repair-deficient human cells. Cancer Res., 51: 2587-2592.

 

5)  Maher, V.M., J.-L Yang, R.-H. Chen, W.G. McGregor, L. Lukash, J.M. Scheid, D.S. Reinhold, and J.J. McCormick (1991) Use of PCR amplification of cDNA to study mechanisms of human cell mutagenesis and malignant transformation. Envirn. and Molec. Mutagen, 18: 239-244.

 

6)  Chen, R.-H., V.M. Maher, J. Brouwer, P. van de Putte, and J.J. McCormick (1992) Preferential repair and strand-specific repair of benzo[a]pyrene diol epoxide adducts in the HPRT gene of diploid human fibroblasts. Proc. Natl. Acad. Sci. (USA), 89: 5413-5417.

 

7)  Chen, R.-H., R. Ebner, and R. Derynck (1993) Inactivation of the type II receptor reveals two receptor pathways for the diverse TGF-β activities. Science, 260: 1335-1338.

 

8)  Ebner, R., R.-H. Chen, L. Shum, S. Lawler, T. F. Zioncheck, A. Lee, A. R. Lopez, and R. Derynck (1993) Cloning of a type I TGF-β receptor and its effect on TGF-β binding to the type II receptor. Science, 260: 1344-1348.

 

9)  Ebner, R., R.-H. Chen, S. Lawler, T. F. Zioncheck, and R. Derynck (1993) Determination of type I receptor specificity by the type II receptors for TGF-β or activin. Science, 262: 900-902.


10)  Chen, R.-H., and R. Derynck (1994) Homomeric interactions between type II transforming growth factor-β receptors. J. Biol. Chem., 269: 22868-22874.


11)  Chen, R.-H., H. L. Moses, E. M. Maruoka, R. Derynck and M. Kawabata (1995) Phosphorylation-dependent interaction of the cytoplasmic domains of the type I and type II transforming growth factor-β receptors. J. Biol. Chem., 270: 12235-12241.


12)  McGregor, W. G., M. C.-M. Mah, R.-H. Chen, V. M. Maher and J. J. McCormick (1995) Lack of correlation between degree of interference with transcription and rate of strand specific repair in the HPRT gene of diploid human fibroblasts. J. Biol. Chem., 270: 27222-27227.

13)  Chen, R.-H., P. Miettinen, E. M. Maruoka, L. Choy and R. Derynck (1995) A WD-domain protein that is associated with and phosphorylated by the type II TGF-β receptor. Nature, 377: 548-552.


14)  Lawler, S., X-H. Feng, R.-H. Chen, E. M. Maruoka, C. W. Turck, I. Griswold-Plenner, and R. Derynck (1997) The type II transforming growth factor-β receptor autophosphorylates not only on serine and threonine but also on tyrosine residues. J. Biol. Chem., 272: 14850-14859.


15)  Chen, R.-H.*, and T.-Y. Chang (1997) Involvement of caspase family proteases in transforming growth factor-β-induced apoptosis. Cell Growth & Diff., 8: 821-827.


16)  Verlhac, M.-H., R.-H. Chen, P. Hanachi, J.W.B. Hershey and R. Derynck (1997) Identification of partners of TIF34, a component of the yeast eIF3 complex, required for cell proliferation and translation initiation. EMBO J., 16: 6812-6822.


17)  McGregor, W.G., D. Wei, R.-H. Chen, V. M. Maher, J. J. McCormick (1997) Relationship between adduct formation, rates of excision repair and the cytotoxic and mutagenic effects of structurally-related polycyclic aromatic carcinogens. Mutat Res., 376: 143-152. 


18)  Chen, R.-H.*, Y.-H. Su, R. L. C. Chuang, and T.-Y. Chang (1998) Suppression of transforming growth factor-β-induced apoptosis through a phosphatidylinositol 3-kinase/Akt-dependent pathway. Oncogene, 17: 1959-1968.


19)  Chen, R.-H., M.-C. Chang, Y.-H. Su, Y.-T. Tsai, and M.-L. Kuo. (1999) Interleukin-6 inhibits transforming growth factor-β-induced apoptosis through the phosphatidylinositol 3-kinase/Akt and signal transducers and activators of transcription 3 pathways. J. Biol. Chem., 274: 23013-23019.


20)  Tsai, Y.-T., 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) Etk, a Btk family tyrosine kinase, mediates cellular transformation by linking Src to STAT3 activation. Mol. Cell. Biol., 20: 2043-2054.
 

21)  Liang, C.-L., C.-N. Tsai, P.-J. Chung, J.-L. Chen, C.-M. Sum, R.-H. Chen, J.-H. Hong and Y.-S. Chang. (2000) 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. Virology, 277: 184-192.

33)  Kuo, J.-C., W.-J. Wang, C.-C. Yao, P.-R. Wu, and R.-H. Chen* (2006) The tumor suppressor DAPK inhibits cell motility by blocking the integrin-mediated polarity pathway. J. Cell Biol., 172: 619-631. 


34)  Wang, W.-J., 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) The tumor suppressor DAPK is reciprocally regulated by tyrosine kinase Src and phosphatase LAR. Mol. Cell, 27: 701-716. 

  • Featured in Science STKE


35)  Chuang Y.-T., L.-W. Fang, M.-H. Lin-Feng, R.-H. Chen, and M.-Z. Lai. (2008) The tumor suppressor death-associated protein kinase targets to TCR-stimulated NF-kB activation. J. Immunology, 180: 3238-3249. 


36)  Lin, Y.-M., Y.-R. Chen, J-R. Lin, W.-J. Wang, A. Inoko, M. Inagaki, Y.-C. Wu and R.-H. Chen*. (2008) eIF3k regulates apoptosis in epithelial cells by releasing caspase 3 from keratin-containing inclusions. J Cell Sci., 121: 2382-2393. 


37)  Shen, C-H., H.-Y. Chen, M.-S. Lin, F.-Y. Li, C.-C. Chang, M.-L. Kuo, J. Settleman, and R.-H. Chen*. (2008) Breast tumor kinase phosphorylates p190RhoGAP to regulate Rho and Ras and promote breast carcinoma growth, migration and invasion. Cancer Res., 68: 7779-7787.


38)  Tsai, P.-I., H.-H. Kao, C. Grabbe, Y.-T. Lee, A. Ghose, T.-T. Lai, K.-P. Peng, D. Van Vactor, R.H. Palmer, R-H. Chen, S.-R. Yeh and C.-T. Chien. (2008) Fak56 functions downstream of integrin alphaPS3betanu and suppresses MAPK activation in neuromuscular junction growth. (2008) Neural Develop., 3: 26. 


39)  Lee, Y.-R., W.-C. Yuan, H.-C. Ho, C.-H. Chen, H.-M. Shih, and R.-H. Chen*. (2010) The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquitination to control interferon responses. EMBO J., 29: 1748-1761. 

  • Featured in A-IMBN Research Highlight 


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) Tumor suppressor death-associated protein kinase is required for full IL-1β production. Blood, 117: 960-970. 


41)  Wu, P.-R., P.-I. Tsai, G.-C. Chen, H.-J. Chou, Y.-P. Huang, Y.-H. Chen, M.-Y. Lin, A. Kimchi, C.-T. Chien and R.-H. Chen*. (2011) DAPK activates MARK1/2 to regulate microtubule assembly, neuronal differentiation, and tau toxicity. Cell Death Differ., 18: 1507-1520. 

  • Featured in A-IMBN Research Highlight


42)  Chang, C.-C., N.-T. Naik, Y.-S. Huang, J.-C. Jeng, P.-H. Liao, H.-Y. Kuo, C.-C. Ho, Y.-L. Hsieh, C.-H. Lin, N.-J. Huang, N. M. Nandita, C. C. Kung, S.-Y. Lin, R.-H. Chen, K.-S. Chang, T.-H. Huang, and H.-M. Shih. (2011) Structural and functional roles of Daxx SIM phosphorylation in SUMO paralog-selective binding and apoptosis modulation. Mol. Cell, 42: 62-74.

  • Featured in Preview (Mol Cell)

  • Recommended by Faculty of 1000 Biology as “MUST READ” grade

43)  Lee, T. H., C.-H. Chen, F. Suixu, P. Huang, C. Schiene-Fischer, S. Daum, Y. J. Zhang, A. Goate, R.-H. Chen, X. Z. Zhou, and K. P. Lu. (2011) Death-associated protein kinase 1 phosphorylates Pin1 and inhibits its prolyl isomerase activity and cellular function. Mol. Cell, 42: 147-159, 2011. 

  • Featured in Preview (Mol Cell)


44)  Lee, C.-W., S.-J. Leu, R.-Y. Tzeng, S.-F. Wang, S.-C. Tsai, K.-H. Sun, R.-H. Chen, and J.-C. Huang. (2011) Latent membrane protein 1 of Epstein-Barr virus regulates death-associated protein kinase 1 in lymphoblastoid cell line. Virology, 413: 19-25.

 

45)  Yuan, W.-C., Y.-R. Lee, S.-F. Huang, Y.-M. Lin, T.-Y. Chen, H.-C. Chung, C.-H. Tsai, H.-Y. Chen, C.-T. Chiang, C.-K. Lai, L.-T. Lu, C.-H. Chen, D.-L. Gu, Y.-S. Pu, Y.-S. Jou, K. P. Lu, P.-W. Hsiao, H.-M. Shih, and R.-H. Chen*. (2011) A Cullin3-KLHL20 ubiquitin ligase-dependent pathway targets PML to potentiate HIF-1 signaling and prostate cancer progression. Cancer Cell, 20: 214-228. 

  • Recommended by Faculty of 1000 Biology as “MUST READ” grade


46)  Lin, M.-Y., Y.-M. Lin, T. Kao, H.-H. Chuang and R.-H. Chen*. (2011) PDZ-RhoGEF ubiquitination by Cullin-3-KLHL20 controls neurotrophin-induced neurite outgrowth. J. Cell Biol., 193: 985-994. 

  • Featured in Global Medical Discovery

  • Recommended by Faculty of 1000 Biology as “RCOMMENDED” grade


47)  Huang, C.-Y., J.-Y. Chen, S.-C. Wu, C.-H. Tan, R.-Y. Tseng, P.-R. Lu, Y.-F. Wu, R.-H. Chen*, and Y.-C. Wu*. (2012) C. elegans EIF-3.K promotes programmed cell death through CED-3 caspase. PLoS One, 7: e36584. 


48)  Chen, H.-Y., Y.-M. Lin, H.-C. Chung, Y.-D. Lang, C.-J. Lin, J. Huang, W.-C. Wang, F.-M. Lin, Z. Chen, H.-D. Huang, J. Y.-J. Shyy, J.-T. Liang*, and R.-H. Chen*. (2012) miR-103/107 promote metastasis of colorectal cancer by targeting the metastasis suppressors DAPK and KLF4. Cancer Res., 72: 3631-3641.


49)  Chen, R.-H.*, Y.-R. Lee, and W.-C. Yuan. (2012) The role of PML ubiquitination in human malignancies. J. Biomed Sci., 19:81 (invited review).


50)  Tsai, P.-I., M, Wang, H.-H. Kao, Y.-J. Cheng, J. A. Walker, R.-H. Chen, and C.-T. Chien. (2012) Neurofibromin mediates FAK signaling in confining synaptic growth at Drosophila Neuromuscular junctions. J Neuroscience, 32: 16971-16981.


51)  Tsai, P.-I., M. Wang, H.-H. Kao, Y.-J. Cheng, Y.-J. Lin, R.-H. Chen, C.-T. Chien. (2012) Activity-dependent retrograde laminin A signaling regulates synapse growth at Drosophila neuromuscular junctions. Proc. Natl. Acad. Sci. (USA), 109: 17699-17704.


52)  Chen, C.-H., C.-C. Chang, T.-H. Lee, M. Luo, P. Huang, P.-H. Liao, S. Wei, F.A. Li,