Institute of Biological Chemistry, Academia Sinica
rhchen@gate.sinica.edu.tw
+886-2-27855696,6020
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.
TRABID inhibition activates cGAS/STING-mediated anti-tumor immunity through mitosis and autophagy dysregulation.
Chen YH, Chen HH, Wang WJ, Chen HY, Huang WS, Kao CH, Lee SR, Yeat NY, Yan RL, Chan SJ, Wu KP, Chen RH
Nature Communications (2023)
VPS34 K29/K48 branched ubiquitination governed by UBE3C and TRABID regulates autophagy, proteostasis and liver metabolism.
Chen YH, Huang TY, Lin YT, Lin SY, Li WH, Hsiao HJ, Yan RL, Tang HW, Shen ZQ, Chen GC, Wu KP, Tsai TF, Chen RH
Nature Communications (2021)
Usp11 controls cortical neurogenesis and neuronal migration through Sox11 stabilization.
Chiang SY, Wu HC, Lin SY, Chen HY, Wang CF, Yeh NH, Shih JH, Huang YS, Kuo HC, Chou SJ, Chen RH
Science Advances (2021)
BIK ubiquitination by the E3 ligase Cul5-ASB11 determines cell fate during cellular stress. (selected in Special Collection of Articles on Cancer Cell Biology)
Chen FY, Huang MY, Lin YM, Ho CH, Lin SY, Chen HY, Hung MC, Chen RH
J Cell Biol (2019)
Ubiquitination of tumor suppressor PML regulates prometastatic and immunosuppressive tumor microenvironment. (Selected as a highlight in JCI This Month)
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)
Cul3-KLHL20 Ubiquitin Ligase Governs the Turnover of ULK1 and VPS34 Complexes to Control Autophagy Termination. (Highlighted in Editor’s Corner and Selected for a ‘Punctum’ contribution in Autophagy)
Liu CC, Lin YC, Chen YH, Chen CM, Pang LY, Chen HA, Wu PR, Lin MY, Jiang ST, Tai TF, Chen RH
Mol Cell (2016)
K33-Linked Polyubiquitination of Coronin 7 by Cul3-KLHL20 Ubiquitin E3 Ligase Regulates Protein Trafficking. (selected as a Mol Cell Preview and a Research Highlight in Nature Rev Mol Cell Biol)
Yuan WC, Lee YR, Lin SY, Chang LY, Tan YP, Hung CC, Kuo JC, Liu CH, Lin MY, Xu M, Chen ZJ, Chen RH
Mol Cell (2014)
USP11 regulates PML stability to control Notch-induced malignancy in brain tumours.
Wu HC, Lin YC, Liu CH, Chung HC, Wang YT, Lin YW, Ma HI, Tu PH, Lawler SE, Chen RH
Nature Commun (2014)
A Cullin3-KLHL20 Ubiquitin Ligase-Dependent Pathway Targets PML to Potentiate HIF-1 Signaling and Prostate Cancer Progression. (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)
