經歷

榮譽

指導學生獲獎

研究方向

(一) 中心粒相關生理功能探討：中心粒(Centriole)是細胞內不可或缺的構造。中心粒與細胞內蛋白共組成中心體(或稱微管組織中心，MTOC)，這構造對細胞的運動，爬行及細胞分裂均扮演重要的角色。實驗室透過基因編輯(CRISPR/Cas9)建構了一系列中心粒功能異常的細胞株，藉由這些細胞，我們有系統地去了解細胞如何透過中心粒去維持其正常的生理功能。

(二) 纖毛形成與功能維持：纖毛是由中心粒頂端所延伸出來的一個特化構造，功能在參與細胞內的訊息傳遞。已知的研究證實纖毛的結構或功能異常會導致很多遺傳性疾病(ciliopathy)，顯示研究纖毛的重要性。實驗室利用蛋白質譜的方式找到許多參與纖毛生合成過程及功能維持的蛋白，藉由研究這些蛋白的功能，我們希冀可以有效率的解開纖毛與疾病間的關係。

The centriole is an evolutional conserved organelle and can be found in most of the cells in our body. Centrioles are microtubule-based structures that have two major roles in animal cells. In cycling cells, centrioles serve as the core structure of the centrosomes that function as microtubule-organization centers (MTOC). Centrioles also function as basal bodies that seed the assembly of the primary cilia. Abnormalities in the number of centrosomes are commonly found in cancers, and basal body dysfunction has been implicated in many human diseases related to cilia function.

Through a SILAC-based proteomic screen, we have acquired a centriole proteome that allows us to study the role of centrioles in detail. With this centriole proteome, we ‘ve identified many proteins at the centrioles and discover their roles in regulating centrosome or cilia functions. The long-term goal of my research is to understand the biogenesis and function of centrioles/cilia, both in the normal cellular context and disease. Specifically, I will continue to shed light on molecular mechanisms underlying the following processes:
(1) Understand the biological functions of centrioles.
(2) The role of centriole proteins in the regulation of cilia biogenesis and activity.

研究著作

Singh S, Yeat NY, Wang YT, Lin SY, Kuo IY, Wu KP, Wang WJ, Wang WC, Su WC, Wang YC, Chen RH. PTP23 ubiquitination by WDR4 suppresses EGFR and c-MET degradation to define a lung cancer therapeutic target.   Cell Death Dis. 2023 Oct 11;14(10):671. doi: 10.1038/s41419-023-06201-4.

Chiu TY, Lo CH, Lin YH, Lai YD, Lin SS, Fang YT, Huang WS, Huang SY, Tsai PY, Yang FH, Chong WM, Wu YC, Tsai HC, Liu YW, Hsu CL, Liao JC*, Wang WJ*. INPP5E regulates TCR/CD3 complex recruitment to the immune synapse through manipulating phospholipid distribution.   Communications Biology. 2023 Sep 5;6(1):911. doi: 10.1038/s42003-023-05269-0.

Chen YH, Chen HH, Wang WJ, Chen HY, Huang WS, Kao CH, Lee SR, Yeat NY, Yan RL, Chan SJ, Wu KP, Chen RH*. TRABID inhibition activates cGAS/STING-mediated anti-tumor immunity through mitosis and autophagy dysregulation.   Nature Communications. 2023 May 26;14(1):3050. doi: 10.1038/s41467-023-38784-z.

Kao CH, Su TY, Huang WS, Lu XY, Jan WN, Huang HH, and Wang WJ*. TFEB- and TFE3-dependent autophagy activation supports cancer proliferation in the absence of centrosomes.  Autophagy. 2022 Mar 22;1-21. doi: 10.1080/15548627.2022.2051880.

Fan JR, You LR, Wang WJ, Huang WS, Chu CT, Chi YH, Chen HC. Lamin A-mediated nuclear lamina integrity is required for proper ciliogenesis. EMBO Report. 2020 Aug 19:e49680. doi: 10.15252/embr.201949680.

Chi HC, Tsai CY, Wang CS, Yang HY, Lo CH, Wang WJ, Lee KF, Lai LY, Hong JH, Chang YF, Tsai MM, Yeh CT, Wu CH, Hsieh CC, Wang LH, Chen WJ, Lin KH. DOCK6 promotes chemo- and radioresistance of gastric cancer by modulating WNT/β-catenin signaling and cancer stem cell traits. Oncogene. 2020 Aug 4. doi: 10.1038/s41388-020-01390-0.

Chong WM, Wang WJ, Lo CH, Chiu TY, Chang TJ, Liu YP, Tanos B, Mazo G, Tsou MB, Jane WN, Yang TT, Liao JC. Super-resolution microscopy reveals coupling between mammalian centriole subdistal appendages and distal appendages. Elife. 2020 Apr 3; 9. pii: e53580. doi: 10.7554/eLife.53580.

Tsai MH, Muir AM, Wang WJ, Kang YN, Yang KC, Chao NH, Wu MF, Chang YC, Porter BE, Jansen LA, Sebire G, Deconinck N, Fan WL, Su SC, Chung WH, Almanza Fuerte EP, Mehaffey MG; University of Washington Center for Mendelian Genomics, Ng CC, Chan CK, Lim KS, Leventer RJ, Lockhart PJ, Riney K, Damiano JA, Hildebrand MS, Mirzaa GM, Dobyns WB, Berkovic SF, Scheffer IE, Tsai JW, Mefford HC. Pathogenic variants in CEP85L cause sporadic and familial posterior predominant lissencephaly. Neuron. 2020 Apr 22; 106(2): 237-245.e8. doi: 10.1016/j.neuron.2020.01.027.

Huang KC, Wang ML, Chen SJ, Kuo JC, Wang WJ, Nhi Nguyen PN, Wahlin KJ, Lu JF, Tran AA, Shi M, Chien Y, Yarmishyn AA, Tsai PH, Yang TC, Jane WN, Chang CC, Peng CH, Schlaeger TM, Chiou SH. Morphological and Molecular Defects in Human Three-Dimensional Retinal Organoid Model of X-Linked Juvenile Retinoschisis. Stem Cell Reports. 2019 Nov 12; 13(5): 906-923. doi: 10.1016/j.stemcr.2019.09.010. 

Lo CH, Lin IH, Yang TT, Huang YC, Tanos BT, Chou PC, Chang CC, Tsay YG, Liao JC, Wang WJ. Phosphorylation of CEP83 by TTBK2 is necessary for cilia initiation. J Cell Biol. 2019. Aug 27. pii: jcb.201811142. doi: 10.1083/jcb.201811142.

Chang CH, Zanini M, Shirvani H, Cheng JS, Yu H, Feng CH, Mercier AL, Hung SY, Forget A, Wang CH, Cigna SM, Lu IL, Chen WY, Leboucher S, Wang WJ, Ruat M, Spassky N, Tsai JW, Ayrault O. Atoh1 Controls Primary Cilia Formation to Allow for SHH-Triggered Granule Neuron Progenitor Proliferation. Dev Cell. 2019 Jan 28;48(2):184-199.e5.

Hsiao CJ, Chang CH, Ibrahim RB, Lin IH, Wang CH, Wang WJ, Tsai JW. Gli2 modulates cell cycle re-entry through autophagy-mediated regulation of the length of primary cilia. J Cell Sci. 2018 Dec 17;131(24)

Hsu WH, Wang WJ, Lin WY, Juang YM, Lai CC, Liao JC, and Chen HC. Adducin-1 is essential for spindle pole integrity through its interaction with TPX2. EMBO Report. 2018 Aug;19(8). pii: e45607. doi: 10.15252/embr.201745607. Epub 2018 Jun 19.

Weng RR, Yang TT, Huang CE, Chang CW, Wang WJ, Liao JC. Super-Resolution Imaging Reveals TCTN2 Depletion-Induced IFT88 Lumen Leakage and Ciliary Weakening. J Biophys J. 2018 Jun 1. pii: S0006-3495(18)30622-2.

Yang TT, Chong WM, Wang WJ, Mazo G, Tanos B, Chen Z, Tran TMN, Chen YD, Weng RR, Huang CE, Jane WN, Tsou MB, Liao JC. Super-resolution architecture of mammalian centriole distal appendages reveals distinct blade and matrix functional components. Nat Commun. 2018 May 22;9(1):2023. doi: 10.1038/s41467-018-04469-1.

Li HR, Chiang WC, Chou PC, Wang WJ, Huang JR. TAR DNA-binding protein 43 (TDP-43) liquid-liquid phase separation is mediated by just a few aromatic residues. J Biol Chem. 2018 Apr 20;293(16):6090-6098. doi: 10.1074/jbc.AC117.001037. Epub 2018 Mar 6.

He Mu, Ye WN, Wang WJ, Sison E, Jan YN, Jan LY. Mammalian calcium activated chloride channel drives epithelium morphogenesis through control of phosphoinositides. PNAS. 2017 Dec 26;114(52):E11161-E11169. doi: 10.1073/pnas.1714448115. Epub 2017 Dec 11.

Chen HY, Wu CT, Tang CC, Lin YN, Wang WJ, Tang TK. Human microcephaly protein RTTN interacts with STIL and is required to build full-length centrioles. Nat Commun. 2017 Aug 15;8(1): 247. doi: 10.1038/s41467-017-00305-0.

Mazo G, Soplop N, Wang WJ, Uryu K, Tsou MB. Spatial Control of Primary Ciliogenesis by Subdistal Appendages Alters Sensation-Associated Properties of Cilia. Dev Cell. 2016 Nov 21;39(4):424-437.

Wang WJ, Acehan D, Kao CH, Jane WN, Uryu K, Tsou MF. 2015. De novo centriole formation in human cells is error-prone and does not require SAS-6 self-assembly. Elife26;4. pii: e10586.

Yang TT, Su J, Wang WJ, Craige B, Witman GB, Tsou MF, Liao JC. 2015. Superresolution Pattern Recognition Reveals the Architectural Map of the Ciliary Transition Zone. Sci Rep.14;5:14096.

Izquierdo D, Wang WJ, Uryu K, Tsou MF. 2014. Stabilization of cartwheel-less centrioles for duplication requires CEP295-mediated centriole-to-centrosome conversion. Cell Rep. 21;8(4):957-65.

Wang WJ, Tay HG, Soni RK, Perumal GS, Goll MG, Macaluso FP, Asara JM, Amack JD, Tsou MF. 2013. CEP162 is an axoneme-recognition protein promoting transition zone assembly at the cilia base. Nature Cell Biol. 15(6): 591-601.

Tanos BE, Yang HJ, Soni RK, Wang WJ, Macaluso FP, Asara JM, Tsou MF. 2013. Centriole-distal appendages promote membrane docking, leading to cilia initiation. Genes&Dev. 27(2): 163-8.

Wang WJ, Soni RK, Uryu K, Tsou MF. 2011. The conversion of centrioles to centrosome: essential coupling of duplication with segregation. J Cell Biol. 193(4): 727-39.

Tsou MF, Wang WJ, George KA, Uryu K, Stearns T, Jallepalli PV. 2009. Polo kinase and separase regulate the mitotic licensing of centriole duplication in human cells. Dev. Cell. 17(3): 344-354 (co-first author)

Lin YM, Chen YR, Lin JR, Wang WJ, Inoko A, Inagaki M, Wu YC, and Chen RH. 2008. eIF3k regulates apoptosis in epithelial cells by releasing caspase 3 from keratin-containing inclusion. J Cell Sci. 121(Pt 14): 2382-93.

Wang WJ, Kuo JC, Ku W, Lee YR, Lin FC, Chang YL, Lin YM, Chen CH, Huang YP, Chiang MJ, Yeh SW, Wu PR, Shen CH, Wu CT, and Chen RH. 2007. The tumor suppressor DAPK is reciprocally regulated by tyrosine kinase Src and phosphatase LAR. Mol. Cell. 27(5): 701-16. (selected as “The Editors’ choice in Sci. STKE,” 2007. Reciprocal regulation of DAPK. Issue 403, p.331)

Kuo JC, Wang WJ, Yao CC, Wu PR, and Chen RH. 2006. The tumor suppressor DAPK inhibits cell motility by blocking integrin-mediated polarity pathway. J Cell Biol. 172(4): 619-31.

Chen RH, Wang WJ, and Kuo JC. 2006. The tumor suppressor DAP-kinase links cell adhesion and cytoskeleton reorganization to cell death regulation. J Biomed Sci. 13(2): 193-199.

Chen CH, Wang WJ, Kuo JC, Tsai HC, Lin JR, Chang ZF, Chen RH. 2005. Bidirectional signals transduced by DAPK-ERK interaction promote the apoptotic effect of DAPK. EMBO J. 24(2): 294-304.

Wang WJ, Kuo JC, Yao CC, Chen RH. 2002. DAP-kinase induces apoptosis by suppressing integrin activity and disrupting matrix survival signals. J Cell Biol. 159(1): 169-79.

Lin KH, Wang WJ, Wu YH, Cheng SY. 2002. Activation of antimetastatic Nm23-H1 gene expression by estrogen and its alpha-receptor. Endocrinology. 143(2): 467-75.