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張佩靖 Amy P. Chang

張佩靖 (Amy Pei-Ching Chang)   

Office:傳醫大樓R306 

e-mail: pcchang@ym.edu.tw

Phone: 886-2-2826-7111


Education/學歷:

國立陽明大學    藥理學研究所            碩士

國立陽明大學       生化暨分子生物研究所    博士

University of Kentucky                                          Postdoctoral fellow

UC Davis                 Cancer Center                 Postdoctoral fellow


Position/
經歷

2016 - Present 副教授, 國立陽明大學            微生物及免疫學研究所

2016 - 2019    副研究員, 高雄醫學大學          傳染病與癌症研究中心

2015 - 2016   Visiting Scholar, School of Pharmacy   University of South California (USC)

2011 - 2016   助理教授, 國立陽明大學          微生物及免疫學研究所

 

Research

(I) Virus-Host interaction: Epigenetic regulation and Cancer

Epigenetic regulation includes: (1) DNA methylation; (2) Histone methylation and (3) Long non-coding RNAs (LncRNAs).

By using oncogenic herpesvirus KSHV as a model, we studied the tumorigenic role of JMJD2A, the first identified histone trimethyl demethylase,

and its own modification in epigenetic regulation. We found that JMJD2A is important for maintain low levels of H3K9me3,

a favorable chromatin environment to execute rapid transcriptional reprograming. JMJD2A was targeted and sumoylated by KSHV K-bZIP,

a viral SUMO E3 ligase. Sumoylation is essential for chromatin binding and in vivo dementylation function of JMJD2A.

Our study also showed the role of JMJD2A in regulating IFN response and how virus against human immune system through targeting JMJD2A.

Nowadays, we use KSHV as a model to identify novel KSHV reactivation associated long non-coding RNAs (lncRNAs),

a newly emerged epigenetic regulator, and elucidate their tumorigenic role.

 

 

 

(II) Virus-Host interaction: Epigenetic regulation and Cancer

I further extend our epigenetic study to prostate cancer (PCa) research. PCa is a leading cancer affecting male population. 
Thought it can be successful treated by androgen deprivation therapy (ADT), unfortunately, 
hormone refractory prostate cancer (HRPC) eventually relapsed within few years after successful treatment. 
Thought 2nd generation of AR antagonist was developed and used for treating HRPC, it induced neuroendocrine differentiation (NED) of PCa cells.
This emerging type of
PCa, so-called NEPC, is highly metastatic and chemoresistant.
We identified
repressor element-1 (RE-1) silencing transcription factor (REST) as a key regulator for. Following this observation,
we
also demonstrated that long-term REST knockdown not only induce NED but also enhanced cell stemness through epigenetic regulation of Twist1 and CD44.
In addition, we identified MAOA,
a decision maker of apoptosis (inhibition) and autophagy (activation), as a novel REST target gene.
It involves in mediating mitophagy activation during NED of PCa cells. Nowadays,
we use
NED as a model and identified many novel NED regulatory lncRNAs, including HOTAIR.

 

 

(III) Cancer Immunology

Emerging evidence showed that microenvironment shaped by pro- and anti-inflammatory types of macrophages contribute to not only host defense, but also cancer progression.
We found that cancer stem cells (CSCs), without affect macrophage phenotype, induce M1 macrophages producing NED-related cytokines.
Integrating transcriptome profiling in combine with mass spectrometry metabolites analysis reveals the contribution of glycolysis pathway in NED-related cytokines production.
Importantly, CSC-educated M1 macrophages induced NED of cancer cells, thereby shifting carcinoma reprograming toward a neuroendocrine (NE) fate.
In tumor tissues, NE marker CgA expression is associated with M1, but not M2, marker.
These findings offer therapeutic opportunities of using immunotherapy to prevent the induction of a more malignant cancer phenotype.

 

 

 

 

 

 

Publications:

1.W.S. YangT.Y. Lin, L. Chang, W.W. Yeh, S.C. Huang, T.Y. Chen, Y.T. Hsieh, S.T. Chen, W.C. Li, C.C. Pan, M. Campbell, C.H. Yen, Y.A. Chen, P.C. Chang*HIV-1 Tat Interacts with a Kaposi's Sarcoma-Associated Herpesvirus Reactivation-Upregulated Antiangiogenic Long Noncoding RNA, LINC00313, and Antagonizes Its Function” J. Virol. (Nov 2019)
2.C.J. Lin, L. Chang, H.W. Chu, H.J. Lin, P.C. Chang, R.Y.L. Wang, B. Unnikrishnan, J.Y. Mao, S.Y. Chen, C.C. Huang “High Amplification of the Antiviral Activity of Curcumin through Transformation into Carbon Quantum Dots” Small (Oct 2019)
3.R. Kant, C.H. Yen, J.H. Hung, C.K. Lu, C.Y. Tung, P.C. Chang, Y.H. Chen, Y.C. Tyan, Y.A. Chen “Induction of GNMT by 1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranoside through proteasome-independent MYC downregulation in hepatocellular carcinoma” Scientific Reports (Feb 2019)
4.Y.T. Chang, T.P. Lin, J.T. Tang, M. Campbell, Y.L. Luo, S.Y. Lu, C.P. Yang, T.Y. Cheng, C.H. Chang, T.T. Liu, C.H. Lin, H.J. Kung, C.C. Pan, P.C. Chang*HOTAIR is a REST-regulated LncRNA that Promotes Neuroendocrine Differentiation in Castration Resistant Prostate Cancer” Cancer Letters (Oct 2018)
5.W.S. Yang, M. Campbell, H.J. Kung, P.C. Chang* In vitro SUMOylation Assay to Study SUMO E3 Ligase Activity” JoVE (Jan 2018)
6.Y.C. Lin, Y.T. Chang, M. Campbell, H.C. Lee, J. C. Shih, P.C. Chang* MAOA- a novel decision maker of apoptosis and autophagy in hormone refractory neuroendocrine prostate cancer cells” Scientific Reports (Apr 2017)
7.Y.H. Liu, J.W. Tsai, J.L. Chen, W.S. Yang, P.C. Chang, P.L. Cheng, D.L. Turner, Y. Yanagawa, T.W. Wang, J.Y. Yu “Ascl1 promotes tangential migration and confines migratory routes by induction of Ephb2 in the telencephalon.” Scientific Reports (Mar 2017)
8.Y.T. Chang, T.P Lin, M. Campbell, C.C. Pan, S.H. Lee, H.C. Lee, M.H. Yang, H.J. Kung, P.C. Chang* “REST is a crucial regulator for acquiring EMT-like and stemness phenotypes in hormone-refractory prostate cancer” Scientific Reports (Mar 2017)
9.W.S.Yang, M. Campbell, P.C. Chang*SUMO modification of a heterochromatin histone demethylase JMJD2A enables viral gene transactivation and viral replication.” PLoS Pathogens (Feb 2017)
10.P.C. Chang*, M. Campbell, E.S. Robertson “Human Oncogenic Herpesvirus and Post-translational Modifications – Phosphorylation and SUMOylation” Frontiers in Microbiology (Jun 2016)
11.T.P. Lin, Y.T. Chang, S.Y. Lee, M. Campbell, T.C. Wang, S.H. Shen, H.J. Chung, Y.H. Chang, Allen W Chiu, C.C. Pan, C.H. Lin, C.Y. Chu, H.J. Kung, C.Y. Cheng, P.C. Chang* “REST modulates hypoxia-induced neuroendocrine differentiation of prostate cancer cells by activating autophagy signaling” Oncotarget (Mar 2016)
12.W.S. Yang, H.W. Hsu, M. Campbell, C.Y. Cheng, P.C. Chang* “K-bZIP mediated SUMO-2/3 specific modification on the KSHV genome negatively regulates lytic gene expression and viral reactivation”  PLoS Pathogens (Jun 2015)
13.P.C. Chang* and H.J. Kung “SUMO and KSHV Replication” Cancers (Basel) (Sep 2014)
14.P.C. Chang*, T.Y. Wang, Y.T. Chang, C.Y. Chu, C.L. Lee, H.W. Hsu, T.A. Zhou, Z. Wu, R.H. Kim, S.J. Desai, S. Liu, H.J. Kung “Autophagy Pathway Is Required for IL-6 Induced Neuroendocrine Differentiation and Chemoresistance of Prostate Cancer LNCaP Cells” PLoS One (Feb 2014)
15.M. Campbell, K.Y. Kim, P.C. Chang, S. Huerta, B. Shevchenko, D.H. Wang, C. Izumiya, H.J. Kung, Y. Izumiya “A Lytic Viral Long Non-coding RNA Modulates the Function of a Latent Protein” J Virol. (Feb 2014)
16.C.Y. Cheng, C.H. Chu, H.W. Hsu, F.R. Hsu, C.Y. Tang, W.C. Wang, H.J. Kung, P.C. Chang* “An improved ChIP-seq peak detection system for simultaneously identifying post-translational modified transcription factors by combinatorial fusion, using SUMOylation as an example” BMC Genomics (Jan 2014)
17.P.C. Chang*, C.Y. Cheng, M. Campbell, Y.C. Yang, H.W. Hsu, T.Y. Chang, C.H. Chu, Y.W. Lee, C.L. Hung, S.M. Lai, C.G. Tepper, W.P. Hsieh, H.W. Wang, C.Y. Tang, W.C. Wang, H.J. Kung “The chromatin modification by SUMO-2/3 but not SUMO-1 prevents the epigenetic activation of key immune-related genes during Kaposi's sarcoma associated herpesvirus reactivation.” BMC Genomics (Nov 2013)
18.M. Campbell, P.C. Chang, S. Huerta, C. Izumiya, R. Davis, C.G. Tepper, K.Y. Kim, B. Shevchenko, D.H. Wang, J.U. Jung, P.A. Luciw, H.J. Kung, Y. Izumiya “Protein Arginine Methyltransferase 1-directed Methylation of Kaposi Sarcoma-associated Herpesvirus Latency-associated Nuclear Antigen” J Biol Chem. (Feb 2012)
19.P.C. Chang*, L.D. Fitzgerald, D.A. Hsia, Y. Izumiya, C.Y. Wu, W.P. Hsieh, S.F. Lin, M. Campbell, K.S. Lam, P.A. Luciw, C.G. Tepper, H.J. Kung Histone demethylase JMJD2A regulates Kaposi's sarcoma-associated herpesvirus replication and is targeted by a viral transcriptional factorJ Virol. (Apr 2011)
20.P.C. Chang*, Y. Izumiya, C.Y. Wu, L.D. Fitzgerald, M. Campbell, T.J. Ellison, K.S. Lam, P.A. Luciw, H.J. Kung “Kaposi's sarcoma associated herpesvirus (KSHV) encodes a SUMO E3 ligase which is SIM-dependent and SUMO-2/3-specific” J Biol Chem (Feb 2010)
21.Z. Wu, P.C. Chang, J.C. Yang, C.Y. Chu, L.Y. Wang, N.T. Chen, A.H. Ma, S.J. Desai, S.H. Lo, C.P. Evans, K.S. Lam, and H.J. Kung “Autophagy Blockade Sensitizes Prostate Cancer Cells towards Src Family Kinase Inhibitors” Genes & Cancer (Jan 2010)
22.P.C. Chang*, L.D. Fitzgerald, A. Van Geelen, Y. Izumiya, T.J. Ellison, D.H. Wang, D.K. Ann, P.A. Luciw, and H.J. Kung “KRAB domain-associated protein-1 as a latency regulator for Kaposi’s sarcoma-associated herpesvirus and its modulation by the viral protein kinase” Cancer Res (Jul 2009)
23.P. C. Chang* and M. Li “Kaposi's sarcoma-associated herpesvirus K-cyclin interacts with Cdk9 and stimulates Cdk9-mediated phosphorylation of p53 tumor suppressor” J Virol, (Jan 2008)
24. P. C. Chang*, C.W. Chi, G.Y. Chau, F.Y. Li, Y.H. Tsai, J.C. Wu and Y.H.W. Lee “DDX3, a DEAD box RNA helicase, is deregulated in hepatitis virus associated hepatocellular carcinoma and is involved in cell growth control” Oncogene, (Mar 2006)  

 

歷屆畢業生:

  • 楊奕程 (碩士: 2011/09 ~ 2013/06) (論文發表: BMC Genomics. 2013 Nov 23; 14:824)
  • 張怡婷 (碩士: 2011/09 ~ 2013/06) (論文發表: PLoS One. 2014 Feb 14; 9(2):e88556)

                   (博士: 2014/09 ~ 2018/09) (1st author 發表: Scientific Reports 2017. Mar  3; 7:42795)

                                      Scientific Reports 2017.  Apr 12; 7:46338

                                      Cancer Letters 2018. Oct 1; 433:43

  • 李松遠 (碩士: 2013/09 ~ 2015/06) (論文發表: Oncotarget. 2016 May 3; 7(18):26137)
  • 楊宛珊 (碩士: 2013/09 ~ 2015/06) (1st author 發表: PLoS Pathog. 2015 Jul 21; 11(7):e1005051.)

                     (博士: 2015/09 ~ Present)          PLoS Pathog. 2017 Feb 17;13(2):e1006216.

                                                         JoVE. 2018 Jan 29; (131)

                                                         J Virol. 2019 Nov 13.

  • 張景欣 (博士: 2015/09 ~ Present)
  • 羅勻里、黃詩晴 (碩士: 2015/09 ~ 2017/06)
  • 楊佳蓓、李悅誠 (碩士: 2016/09 ~ 2018/06)
  • 張龍 (博士: 2016/09 ~ Present)
  • 鄭庭伃 (碩士: 2017/09 ~ 2019/06)
  • 林庭宇 (碩士: 2017/09 ~ 2019/06) (論文發表: J Virol. 2019 Nov 13 [與楊宛珊並列第一作者])
  • 葉葳 (碩士: 2017/09 ~ 2019/06)
  • 江玟慧 (碩士: 2017/09 ~ 2019/06)
  • 施文仁 (碩士: 2017/09 ~ 2019/06)
  • 高晨媗 (碩士: 2018/09 ~ Present)
  • 沈彩文 (碩士: 2019/09 ~ Present)

 

 

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