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Dr. Ruey-Hwa  Chen
Distinguished Research Fellow
Room 602, Institute of Biological Chemistry, Academia Sinica
128, Academia Road Sec. 2, Nankang, Taipei 115, Taiwan
TEL: +886-2-2785-5696 ext. 6020
FAX: +886-2-2788-9759
rhchen@gate.sinica.edu.tw

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.

1987, 09 - 1991, 12 Ph.D, Biochemistry, Michigan State University
1983, 09 - 1985, 06 M.S., Biochemistry, National Taiwan University
1979, 09 - 1983, 06 B.S., Agricultural Chemistry, National Taiwan University

2012,07 - present Distinguished Research Fellow, Institute of Biological Chemistry, Academia Sinica
2006,08 - 2012,07 Research Fellow, Institute of Biological Chemistry, Academia Sinica
2003,08 - 2006,07 Professor, Institute of Molecular Medicine, College of Medicine, National Taiwan University
1996,02 - 2003,07 Associate Professor, Institute of Molecular Medicine, College of Medicine, National Taiwan University
1995,10 - 1996,02 Assistant Biochemist, University of California at San Francisco
1992,01 - 1995,09 Postdoctoral Fellow, University of California at San Francisco

    Publications List
K33-linked polyubiquitination of coronin 7 by Cul3-KLHL20 ubiquitin ligase regulates protein trafficking. (selected as a Mol Cell Preview and a Research Highlight in Nature Rev Mol Cell Biol)
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)
Regulation of inflammation by DAPK. (invited review)
M.-Z. Lai and R.-H. Chen Apoptosis (2014)
SCP phosphatases suppress renal cell carcinoma by stabilizing PML and inhibiting mTOR/HIF signaling.
Lin YC, Lu LT, Chen HY, Duan X, Lin X, Feng XH, Tang MJ, Chen RH Cancer Research (2014)
The functions and regulations of DAPK in cancer metastasis. (invited review)
Chen, H.-Y., Y.-R. Lee, and R.-H. Chen Apoptosis (2014)
USP11 stabilizes PML to control Notch-induced malignancy in brain tumors.
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)
miR-103/107 promote metastasis of colorectal cancer by targeting the metastasis suppressors DAPK and KLF4.
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)
A Cullin3-KLHL20 Ubiquitin Ligase-Dependent Pathway Targets PML to Amplify HIF-1 Signaling and Tumor Hypoxia responses. (recommended by Faculty of 1000 Biology as F1000 factor 9.0 “MUST READ” grade)
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)
DAPK activates MARK1/2 to regulate microtubule assembly, neuronal differentiation, and tau toxicity. (selected as A-IMBN Research highlight)
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)
PDZ-RhoGEF ubiquitination by Cullin3-KLHL20 controls neurotrophin-induced neurite outgrowth. (highlighted by Global Medical Discovery and recommended by Faculty of 1000 Biology as F1000 factor 6.0 “RCOMMENDED” grade)
Lin MY, Lin YM, Kao TC, Chuang HH, Chen RH Journal of cell biology (2011)
The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquitination to control interferon responses. (selected as A-IMBN Research highlight)
Lee Y.-R., W.-C. Yuan, H.-C. Ho, C.-H. Chen, H.-M. Shih, and R.-H. Chen EMBO J (2010)

Updated 2017.03.08

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