◎學歷◎

高雄醫學大學醫學研究所博士

◎專長領域◎

癌細胞轉移;淋巴血管新生;癌細胞抗藥性機制;基因突變修復機制

◎研究方向◎

腫瘤的多樣性一直是造成治療成效上的瓶頸。因此，個人化的治療是近年來不論是臨床醫學或基礎研究一直著力發展及探討的主軸。本實驗室研究方向著重在探討癌細胞轉移及血管新生的分子機制。想藉由其中了解，進而研發具有專一性的標的以用來做為臨床診斷上的工具及藥物的開發。

除此之外，抗藥性細胞株的產生是造成臨床上治療失敗的原因。為了有效改善病人用藥的效果進而提升病人的存活率，以期許能做為個人化治療的方針。近年來，我們實驗室利用基因體學和蛋白質體學分析技術來試圖找出新特定蛋白表現與藥物或放射線治療成效的相關性。我們發現，表異質基因調控酵素(Epigenetic modification enzymes)對於癌細胞轉移和抗藥性細胞株產生扮演重要角色。已知癌細胞惡性化的表徵與癌幹細胞有著密不可分的關係存在。因此，本實驗室特別就針對表異質基因調控酵素與癌細胞轉移、抗藥性細胞株產生及幹細胞特性做為研究主軸。希望此研究方向不僅可以找出針對癌症幹細胞的新穎治療藥物，也有助於臨床上診斷，以有效解決臨床醫學所面臨的問題。

◎經歷◎

MD Anderson Cancer Ctr., Houston, TX 博士後研究員 (2008-2011)

國家衛生研究院癌症研究所博士後研究員 (2011-2013)

高雄醫學大學臨床醫學研究所助理教授（2013~2018.01）

高雄醫學大學臨床醫學研究所副教授（2018.02~2021.01）

高雄醫學大學臨床醫學研究所教授（2021.02~）

高雄醫學大學附設中和紀念醫院臨床醫學研究部癌症研究室主任（2021.08~)

◎期刊論文發表◎

        (Selected) 

1.    Ou-Yang F, Li CL, Chen CC, Shen YC, Moi SH, Luo CW, Xia W, Wang YN, Lee HH, Wang LH, Wang SC*, Pan MR*, Hou MF*, Hung MC*. De-glycosylated membrane PD-L1 in tumor tissues as a biomarker for responsiveness to atezolizumab (Tecentriq) in advanced breast cancer patients. American Journal of Cancer Research. 2022;12(1):123-137.

2.    Kao CN, Moi SH, Hou MF, Luo CW, Chen FM, Pan MR. RNF8-CDH1 Co-Expression Predicts Clinical Benefit of Chemoradiotherapy in Triple-Negative Breast Cancer. Journal of personalized medicine. 2021 Jul 13;11(7):655.

3.      Lee HH, Wang YN, Yang WH, Xia W, Wei Y, Chan LC, Wang YH, Jiang Z, Xu S, Yao J, Qiu Y, Hsu YH, Hwang WL, Yan M, Cha JH, Hsu JL, Shen J, Ye Y, Wu X, Hou MF, Tseng LM, Wang SC, Pan MR, Yang CH, Wang YL, Yamaguchi H, Pang D, Hortobagyi GN, Yu D, Hung MC. Human ribonuclease 1 serves as a secretory ligand of ephrin A4 receptor and induces breast tumor initiation. Nature communications. 2021 May 13;12(1):2788.

4.   Wang HC, Chan LP, Wu CC, Chang SJ, Moi SH, Luo CW, Pan MR. Silencing DNA Polymerase β Induces Aneuploidy as a Biomarker of Poor Prognosis in Oral Squamous Cell Cancer. International Journal of Molecular Sciences.  2021 Feb 27;22(5):2402. doi: 10.3390/ijms22052402.

5.    Wang HC, Chou MC, Wu CC, Chan LP, Moi SH, Pan MR*, Liu TC*, Yang CH*. Application of the Interaction between Tissue Immunohistochemistry Staining and Clinicopathological Factors for Evaluating the Risk of Oral Cancer Progression by Hierarchical Clustering Analysis: A Case-Control Study in a Taiwanese Population. Diagnostics (Basel). 2021 May 21;11(6):925.

6.      Huang WL, Luo CW, Chou CL, Yang CC, Chen TJ, Li CF, Pan MR. High Expression of UBE2B as a Poor Prognosis Factor in Patients With Rectal Cancer Following Chemoradiotherapy. Anticancer Research. 2020 Nov;40(11):6305-6317. doi: 10.21873/anticanres.

7.      Luo CW, Hou MF, Huang CW, Wu CC, Ou-Yang F, Li QL, Wu CC and Pan MR. The CDK6-c-Jun-Sp1-MMP-2  axis as a biomarker and therapeutic target for triple-negative breast cancer. American Journal of  Cancer  Research. 2020 Dec 1;10(12):4325-4341.

8.     Hsu YC, Luo CW, Huang WL, Wu CC, Chou CL, Chen CI, Chang SJ, Chai CY, Wang HC, Chen TY, Li CF, Pan MR. BMI1-KLF4 axis deficiency improves responses to neoadjuvant concurrent chemoradiotherapy in patients with rectal cancer. Radiother Oncol. 2020 Aug;149:249-258. doi: 10.1016/j.radonc.2020.06.023.  

9.     Pan MR, Wu CC, Kan JY, Li QL, Chang SJ, Wu CC, Li CL, Ou-Yang F, Hou MF, Yip HK, Luo CW. Impact of FAK Expression on the Cytotoxic Effects of CIK Therapy in Triple-Negative Breast Cancer. Cancers (Basel). 2019 Dec 30;12(1):94. doi: 10.3390/cancers12010094.

10.   Tsai HL, Pang SY, Wang HC, Luo CW, Li QL, Chen TY, Fang SY, Wang JY, Pan MR. Impact of BMI1 expression on the apoptotic effect of paclitaxel in colorectal cancer. American Journal of Cancer Research. 2019 Nov; 1;9(11): 2544-2553.

11.   Wang HC, Chou CL, Yang CC, Huang WL, Hsu YC, Luo CW, Chen TJ, Li CF, Pan MR. Over-Expression of CHD4 Is an Independent Biomarker of Poor Prognosis in Patients with Rectal Cancers Receiving Concurrent Chemoradiotherapy. International Journal of Molecular Sciences. 2019 Aug 21;20(17). pii: E4087. doi: 10.3390/ijms20174087.

12.   Hung YH, Hsu MC, Chen LT, Hung WC, Pan MR. Alteration of Epigenetic Modifiers in Pancreatic Cancer and Its Clinical Implication. Journal of Clinical Medicine. 2019 Jun 24;8(6). pii: E903. doi: 10.3390/jcm8060903. Review.

13.   Pan MR, Hou MF, Ou-Yang F, Wu CC, Chang SJ, Hung WC, Yip HK, Luo CW*. FAK is required for tumor metastasis-related fluid microenvironment in triple-negative breast cancer. Journal of Clinical Medicine. 2019 Jan 2;8(1). pii: E38. doi: 10.3390/jcm8010038.

14.   
Wang HC, Hung WC, Chen LT, Pan MR. From Friend to Enemy: Dissecting the Functional Alteration of Immunoregulatory Components during Pancreatic Tumorigenesis. International Journal of Molecular Sciences. 2018 Nov 13;19(11). pii: E3584. doi: 10.3390/ijms19113584. Review.1.         

15.   Tian YF, Wang HC, Luo CW, Hung WC, Lin YH, Chen TY, Li CF, Lin CY, Pan MR. Preprogramming therapeutic response of PI3K/mTOR dual inhibitor via the regulation of EHMT2 and p27 in pancreatic cancer. American Journal of Cancer Research. 2018 Sep 1;8(9):1812-1822.

16.  Luo CW, Hsiao IL, Wang JY, Wu CC, Hung WC, Lin YH, Chen TY, Hsu YC, Cheng TL, Pan MR. Cell Motility Facilitated by Mono(2-ethylhexyl) Phthalate via Activation of the AKT-β-Catenin-IL-8 Axis in Colorectal Cancer. Journal of Agricultural and Food Chemistry. 2018 Sep 19;66 (37) :9635-9644.        

17.   Luo CW, Wu CC, Chang SJ, Chang TM, Chen TY, Chai CY, Chang CL, Hou MF, Pan MR. CHD4-mediated loss of E-cadherin determines metastatic ability in triple-negative breast cancer cells. Experimental Cell Research. 2018 Feb 1;363(1):65-72.

18.  Pan MR, Hsu MC, Chen LT, Hung WC. Orchestration of H3K27 methylation: mechanisms and therapeutic implication. Cellular and Molecular Life Sciences. 2018 Jan;75(2):209-223.

19.    Hou MF, Luo CW, Chang TM, Hung WC, Chen TY, Tsai YL, Chai CY, Pan MR. The NuRD complex-mediated p21 suppression facilitates chemoresistance in BRCA-proficient breast cancer. Experimental Cell Research. 2017 Oct 15;359(2):458-465.

20.   Luo CW, Wang JY, Hung WC, Peng Guang, Tsai YL, Chang TM, Chai CY, Lin CH and Pan MR. G9a governs colon cancer stem cell phenotype and chemoradioresistance through PP2A-RPA axis-mediated DNA damage response. Radiotherapy and Oncology. 2017 Sep;124(3):395-402.

21.    Yin HL,Wu CC, Lin CH, Chai CY, Hou MF, Chang SJ, Tsai HP, Hung WC, Pan MR* and Luo CW*. Beta1 Integrin as a Prognostic and Predictive Marker in Triple-Negative Breast Cancer. International Journal of Molecular Sciences 2016 Aug 31;17(9). pii: E1432.

22.   Pan MR, Hsu MC, Chen LT, Shen YS, Hung WC. The histone methyltransferase G9a as a therapeutic target to override gemcitabine resistance in pancreatic cancer. Oncotarget 2016 Sep 20;7(38):61136-61151.

23.  Pan MR, Li Kaiyi, Lin SY and Hung WC. Connecting the Dots: From DNA Damage and Repair to Aging. International Journal of Molecular Sciences. 2016 May 6;17(5).

24.   Pan MR, Hsu MC, Liu JY, Chen LT, Hung WC. G9a orchestrates PCL3 and KDM7A to promote histone H3K27 methylation. Scientific Reports. 2015 Dec 21;5:18709.

25.   Leu MH*, Huang CC*, Pan MR*, Chen HH, Hung WC. Prospero homeobox 1 promotes epithelial-mesenchymal transition in colon cancer cells by inhibiting E-cadherin via miR-9. Clinical Cancer Research. 2012; 18(23): 6416-25.

26.  Peng G, Dai H, Zhang W, Hsieh HJ, Pan MR, Park YY, Tsai RY, Bedrosian I, Lee JS, Ira G, Lin SY. Human Nuclease/Helicase DNA2 Alleviates Replication Stress by Promoting DNA End Resection. Cancer Research. 2012; 72(11): 2802-13.

27.   Pan MR, Hsieh HJ, Dai H, Hung WC, Li K, Peng G, Lin SY. Chromodomain helicase DNA-binding protein 4 (CHD4) regulates homologous recombination DNA repair and its deficiency sensitizes cells to poly (ADP-ribose) polymerase (PARP) inhibitor Treatment. The Journal of Biological Chemistry. 2012; 287 (9): 6764-72.

28.   Pan MR, Peng G, Hung WC, Lin SY. Monoubiquitination of H2AX regulates DNA damage response signaling. The Journal of Biological Chemistry. 2011; 286(32): 28599-607.