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Curriculum Vitae Birth Jun 16, 1982 Phone 886-7-5252000#5820

Address No.70, Lianhai Rd., Gushan Dist., Kaohsiung City 804, Taiwan

Email lwh16@staff.nsysu.edu.tw Gender Female

Education

Ph. D. (Sep, 2006 - Jun, 2011) Institute of Biomedical Sciences, National Sun Yat-Sen University, Taiwan B.A. (Sep, 2000 - Jun, 2004) Department of Nursing, I-Shou University, Taiwan

Employment experiment

Postdoctoral research Fellow (July, 2011 - present) Institute of Biomedical Sciences, National Sun Yat-Sen University Registered Nurse (July, 2004 - Aug, 2005) Department of cardiovascular, Chung Shan Medical University Hospital

Professional Qualifications

Certificate of Registered Nurses

Research Fields 1. Identification of biological function of snake venom proteins 2. Cellular signaling pathway responsible for cytotoxicity of snake

venom proteins toward cancer cell lines 3. Molecular mechanisms involve in proliferation and metastasis of

human leukemic cells 4. The biological function of ADAM17 in malignant cells

Awards and Honors

Jun, 2012 1st Genomic Medicine and Biomarker symposium (poster award and oral presentation award) Oct, 2011 2011 FAOBMB Travel Fellowship award Jun, 2011 The Phi Tau Phi Scholastic Honor Society of the Republic of China Mar, 2011 The 26th Joint Annual Conference of Biomedical Science (poster award) Feb, 2011 19th Symposium on Recent Advances in Cellular and Molecular Biology (poster award) July, 2009 Young Scientist Program award, 21st IUBMB and the 12th FAOBMB International Congress of Biochemistry and Molecular Biology (2009-Congress) Sep, 2004 The Phi Tau Phi Scholastic Honor Society of the Republic of China

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List of Publications in International Journals* 1. Liu, W.H, and Chang, L.S. Suppression of Akt/Foxp3-mediated miR-183

expression blocks Sp1-mediated ADAM17 expression and TNF-mediated NFB activation in piceatannol-treated human leukemia U937 cells. Biochemical Pharmacology. (in press, 2012) (IF 4.705) Liu WH conceived and designed the experiments, performed the experiments, and analyzed the data. Manuscript was written by Liu WH and proofread by Chang LS.

2. Liu, W.H., and Chang, L.S. Fas/FasL-dependent and -independent activation of caspase-8 in doxorubicin-treated human breast cancer MCF-7 cells: ADAM10 down-regulation activates Fas/FasL signaling pathway. Int J Biochem Cell Biol 43, 1708- 1719 (2011) (IF 4.634) Liu WH conceived and designed the experiments, performed the experiments, and analyzed the data. Manuscript was written by Liu WH and proofread by Chang LS.

3. Liu, W.H., and Chang, L.S. Adaphostin promotes caffeine-evoked autoacrine Fas-mediated death pathway activation in Bcr/Abl-positive leukemia cells. Biochem J 439,453-467 (2011) (IF 4.897) Liu WH conceived and designed the experiments, performed the experiments, and analyzed the data.

4. Liu, W.H., and Chang, L.S. Suppression of ADAM17-mediated Lyn/Akt pathways induces apoptosis of human leukemia U937 cells: Bungarus multicinctus protease inhibitor-like protein-1 uncovers the cytotoxic mechanism. J Biol Chem 285, 30506-30515 (2010) (IF 4.773) Liu WH conceived and designed the experiments, performed the experiments, and analyzed the data. Manuscript was written by Liu WH and proofread by Chang LS.

5. Liu, W.H., and Chang, L.S. Piceatannol induces Fas and FasL up-regulation in human leukemia U937 cells via Ca2+/p38 MAPK-mediated activation of c-Jun and ATF-2 pathways. Int J Biochem Cell Biol 42,1498-1506 (2010) (IF 4.634) Liu WH conceived and designed the experiments, performed the experiments, and analyzed the data.

6. Liu, W.H., Chen, K. C., Chiou, Y. L., Lin, S. R., and Chang, L. S. Taiwan cobra phospholipase A2 elicits posttranscriptional up-regulation of ADAM17 in human neuroblastoma SK-N-SH cells. J Cell Biochem 111, 148-157 (2010) (IF 2.868) Chen KC conceived and designed the experiments, Liu WH assisted in performing the experiments, and analyzed the data.

7. Liu, W.H., and Chang, L.S. Caffeine induces matrix metalloproteinase-2 (MMP-2) and MMP-9 down- regulation in human leukemia U937 cells via Ca2+/ ROS-mediated suppression of ERK/c-fos pathway and activation of p38 MAPK/c-jun pathway. J Cell Physiol 224, 775-785 (2010) (IF 3.874) Liu WH conceived and designed the experiments, performed the experiments, and analyzed the data. Manuscript was written by Liu WH and proofread by Chang LS.

8. Chen, Y.J., Liu, W.H., Kao, P.H., Wang, J.J., and Chang, L.S. Involvement of p38 MAPK- and JNK-modulated expression of Bcl-2 and Bax in Naja nigricollis

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CMS-9-induced apoptosis of human leukemia K562 cells. Toxicon 55, 1306- 1316 (2010) (IF 2.508) Liu WH assisted in performing the experiments, and analyzing the data.

9. Chen, K.C., Liu, W.H., and Chang, L.S. Taiwan cobra phospholipase A2-elicited JNK activation is responsible for autocrine fas-mediated cell death and modulating Bcl-2 and Bax protein expression in human leukemia K562 cells. J Cell Biochem 109, 245-254 (2010) (IF 2.868) Liu WH’s contribution to this work was assisted in performing the experiments, and analyzing the data.

10. Chen, K.C., Liu, W.H., Kao, P.H., and Chang, L.S. Calcium-stimulated mitogen-activated protein kinase activation elicits Bcl-xL downregulation and Bak upregulation in notexin-treated human neuro-blastoma SK-N-SH cells. J Cell Physiol 222, 177-186. (2010) (IF 3.874) Liu WH’s contribution to this work was assisted in performing the experiments, and analyzing the data.

11. Chou, W.M., Liu, W.H., Chen, K.C., and Chang, L.S. Structure- function studies on inhibitory activity of Bungarus multicinctus protease inhibitor-like protein on matrix metalloprotease-2, and invasion and migration of human neuroblastoma SK-N-SH cells. Toxicon. 55, 353-360 (2010) (IF 2.508) Liu WH’s contribution to this work was assisted in performing the experiments of cell culture.

12. Chen, K.C., Liu, W.H., and Chang, L.S. Suppression of ERK signaling evokes autocrine Fas-mediated death in arachidonic acid-treated human chronic myeloid leukemia K562 cells. J Cell Physiol 222, 625-634 (2010) (IF 3.874) Liu WH’s contribution to this work was assisted in performing parts of experiments in cell culture and western blotting analysis.

13. Chiou, Y.L., Kao, P.H., Liu, W.H., Lin, S.R. and Chang, L.S. Roles of lysine residues and N-terminal alpha-amino group in membrane-damaging activity of Taiwan cobra cardiotoxin 3 toward anionic and zwitterionic phospholipid vesicles. Toxicon 55, 256-264 (2010) (IF 2.508) Liu WH’s contribution to this work was assisted in performing parts of experiments in cell culture and cell viability analysis.

14. Liu, W.H., and Chang, L.S. Arachidonic acid induces Fas and FasL upregulation in human leukemia U937 cells via Ca2+/ROS-mediated suppression of ERK/c-Fos pathway and activation of p38 MAPK/ATF-2 pathway. Toxicol Lett 191, 140-148 (2009) (IF 3.23) Liu WH conceived and designed the experiments, performed the experiments, and analyzed the data. Manuscript was written by Liu WH and proofread by Chang LS.

15. Liu, W.H., Cheng, Y.C. and Chang, L.S. ROS-mediated p38 MAPK activation and ERK inactivation responsible for upregulation of Fas and FasL and autocrine Fas-mediated cell death in Taiwan cobra phospholipase A2-treated U937 cells. J Cell Physiol 219, 642-651 (2009) (IF 3.874)

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Liu WH conceived and designed the experiments, performed the experiments, and analyzed the data. Manuscript was written by Liu WH and proofread by Chang LS.

16. Liu, W.H., Kao, P.H., Chiou, Y.L., Lin, S.R., Wu, M.J. and Chang, L.S. Catalytic activity-independent pathway is involved in phospholipase A2-induced apoptotic death of human leukemia U937 cells via Ca2+-mediated p38 MAPK activation and mitochondrial depolarization. Toxicol Lett 185, 102-109 (2009) (IF 3.23) Liu WH conceived and designed the experiments, performed the experiments, and analyzed the data.

17. Liu, W.H., Kao, P.H., Lin, S.R. and Chang, L.S. Membrane- damaging activity with A chain and B chain of -bungarotoxin. Toxicon 53, 262-268 (2009) (IF 2.508) Liu WH conceived and designed the experiments, performed the experiments, and analyzed the data.

18. Liu, W.H., and Chang, L.S. Reactive oxygen species and p38 mitogen-activated protein kinase induce apoptotic death of U937 cells in response to Naja nigricollis toxin . J Cell Mol Med 13, 1695-1705 (2008) (IF 4.125)

Liu WH conceived and designed the experiments, performed the experiments, and analyzed the data.

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Abstract Indicate below the abstract that is submitted by you for presentation at the YSP and the FAOBMB Congress in Bangkok (include all authors, affiliation(s) and the text of the abstract)

Foxp3overexpressionup‐regulatesADAM17inducingSrcactivationtopromoteleukemiacellprogression

Wen‐HsinLiuandLong‐SenChang

InstituteofBiomedicalSciences,NationalSunYat‐SenUniversity,Kaohsiung804,Taiwan

ADAM17isamatrixmetalloprotease‐likeenzymeinvolvedinthereleaseofmembrane ligands thathavebeen shown topromoteboth cancer formationandprogression. These ligands include TGF‐a, TNF‐a, amphiregulin, heparin‐bindingepidermalgrowthfactorandepiregulin.Inthisstudy,wefoundthathydroquinone(HQ)induceddeathofleukaemiaU937cells.Moreover,HQmarginallyaffectedtheviabilityofchronicleukemiacells(K562,KU‐812andMEG‐01).Comparedwiththatin U937 cells, ADAM17expression and EGFR phosphorylation were significantlyincreased in chronic leukaemia cells and HQ‐resistant U937 cells. However,gefitinibtreatmentwasunabletoreducecellcolonyformationandproliferationofchronic leukemia cells and HQ‐resistant U937 cells. Meanwhile, knock‐down ofADAM17promotedthecytotoxcityofHQonchronicleukemiacellsandHQ‐resistantU937 cells. Noticeably, ADAM17‐mediated activation of Lyn was involved inmaintaining theviabilityofHQ‐U937cellsand chronic leukemia cells. Moreover,Foxp3‐mediatedmiR‐183 expression was found to block Sp1‐mediated ADAM17expressioninU937cells. Consistently,chronicleukemiccellslineandHQ‐resistantU937 cells had higher Foxp3 expression comparedwithU937 cells. HQ‐inducedFoxp3 and Lyn expression was closely related to epigenetic regulation throughpromotermethylationinU937cells.Collectively,theseresultsprovidenewinsightsinto novel pathways associated with HQ‐induced malignancy of haematologicalcells.

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Personal Statement Indicate briefly here your Research Interests and Career Goals, why you are interested to participate in the YSP Program (including what you will bring to the YSP and what you hope to gain from it): (no more than one page)

My research interests are to address the signalling transduction mechanisms on

promoting carcinogenesis and drug-resistance in leukaemia cells and other carcinoma cells. In the past few years, I have paid efforts on elucidating the molecular mechanisms in apoptosis and invasion of leukemia cells. Moreover, the results of these studies also prove that a crosstalk between p38 MAPK and ERK via protein phosphatase 2A and MKP-1 regulates signalling pathway of leukaemia cells. Meanwhile, our studies reveal the involvement of ADAM17 in Lyn activation in leukemia cells and the functional role of ADAM10 in regulating FasL expression on breast cancer cells. ADAM10 and ADAM17 are well known to involve in ectodomain shedding of membrane substrates such as TNF and EGFR ligands which are closely related to cell proliferation. Thus, I extend my studies on the molecular events responsible for regulating ADAM10/17 genetic regulation, transcription and activity. Moreover, the functional roles of ADAM17 and Lyn in leukemia cell survival pathway and the molecular events associated with ADAM17- and Lyn-mediated pathways will be also studied. Our data indicate that Sp1 is a crucial transcriptional factor for ADAM17 genetic transcription, and that Akt/Foxp3-mediated miR-183 expression closely regulates Sp1-mediated ADAM17 expression in leukaemia cells. Although Foxp3 is recognized as the marker of Treg cell maturation, my preliminary data indicate that Foxp3 expression may be a malignant biomarker and prognostic factor in human leukemia. These findings might suggest novel targets in developing strategy for leukemia therapy.

The functional roles of ADAM17 in leukemia cells are my major project during my Ph.D. course and postdoctoral fellowship in National Sun Yat-Sen University, Taiwan. These trainings and experimental experiences make me familiar with molecular biology and cell biology. Nevertheless, I fell that there is still much room for improving my research ability. I am going to seek for another postdoctoral fellowship in other country or area including USA, European or Japan and expand my scientific horizons. Finally, I hope to get a faulty position from university or research institute in Taiwan, and pursue a research goal in resolving disease mechanism and developing therapeutic modality. To attend the YSP for me is a memorable experience, I enjoyed every moment of it. In 2009, I applied for the YSP program in Shanghai, which is my first time to participate this program. All of things widen my horizon by communicating with researchers from other country and sharing research results, helping each other with research problems, and networking within and beyond their fields of study. These experiences made me open up my mind and developed a global perspective. Last year, I applied the program again in Singapore, and also made me exciting to attend professional academic lectures and learn more knowledge. So that, I wish I can do my best to strive for attending the every FAOBMB program.

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Attachments:

Letters of recommendation from two referees.