放射醫學研究中心

現職

• 長庚大學放射醫學研究院 助理研究員

學歷

• 博士: 私立台北醫學大學醫學科學研究所 (2010~2014)
• 碩士: 私立中山醫學大學生物化學研究所 (2001~2003)
• 學士: 國立中興大學土壤與環境科學系 (1997~2001)

經歷

• 08/2019 ~ now: 助理研究員/放射醫學研究中心/長庚大學       
• 10/2018–07/2019: 博後研究員/分子與基因醫學研究所/國衛院竹南分院                   
• 09/2016–06/2018: 助理研究員/血液腫瘤科/淡水馬偕醫院
• 09/2017–06/2018: 兼任助理教授/視光學科/新生醫專
• 12/2015 –07/2016: 博後研究員/臨床醫學研究所/國立陽明大學
• 09/2006–12/2015: 助理工程師/同位素組/核能研究所

研究領域

輻射生物、癌症生物學、癌症免疫學、生物技術

我目前興趣為探討放射治療影響癌症病人免疫活性的機轉，主要是過去文獻發現放射治療具有遠端效應(Abscopal effect)，並與免疫治療合併具有加乘效果，推測放射治療具有相當程度的免疫活化特性。了解機轉後並想研發藥物及建立臨床上評估免疫抗癌活性的生物標記。我過去於肺癌細胞探討臨床免疫治療檢查哨(checkpoints)的機轉，發現肺癌細胞大量表現免疫抑制受體(例如PD-L1、PVR等)，並證實STAT3-STAT1會促進IFNγ-mediated PD-L1的表現 (Molecular Carcinogenesis. 2018;57:1588-1598.)。臨床上雖然TKIs標靶藥物有效治療肺癌，我們發現肺癌細胞經由STAT3-G9a路徑，會誘導HER3基因大量表達，進而產生TKIs抗性(BMC Cancer. 2019, 19:959)。既然藥物無法完全根治肺癌再復發，我們目前朝向研究免疫抗癌活性，猜想免疫療法應該為未來方向之一。這方面的研究我們發現放射治療可促進免疫抗癌活性(Cells. 2021, 10(10), 2515)；最主要放射治療可誘導癌細胞經由cGAS-STING訊息傳遞表現IFNα，IFNγ 與 CXCL9/10，其中IFNα可活化CD8⁺ T細胞，IFNγ推測可造成巨噬細胞M1極化，而CXCL9/10為趨化因子可促進CD8⁺ T細胞遷移到腫瘤微環境(Biomedicines. 2021, 9, 1349)。CXCL10並且與CD8⁺ T細胞CXCR3受體結合，使CD8⁺ T細胞LFA1活化並可與癌細胞ICAM-1相互作用，增加Synapse的產生以促進CD8⁺ T細胞的抗癌活性(Cancer Immunology Immunotherapy. 2023, 72(6);1865-1880.)。然而，CD8+ T細胞對腫瘤細胞的辨識仍需要CD8+ T細胞的TCR辨識腫瘤MHCI呈現特定抗原，由於我們已在CT26衍生的腫瘤小鼠驗證「HBs表達腫瘤-抗HBs免疫」的抗原識別足以抑制腫瘤生長，我們想利用此特性設計免疫抗癌藥物，設法將HBs蛋白帶入腫瘤細胞並被MHCI呈現，以致活化CD8+ T細胞進而抑制腫瘤。我們接下來想於Syngeneic腫瘤動物模式探討詳細機轉，我們推測放射治療不只活化T細胞，亦會改變巨噬細胞M1極化，主因還是放射治療促使癌細胞表現IFNs。另一方面想針對免疫T細胞研發藥物，因為臨床上免疫治療只有10-30%有效性，或許IFNα或CXCL9/10藥物可增加免疫治療療效(accepted by Cancer Immunology Immunotherapy, 2024)。我們最終期待藉由改變癌病人免疫耗竭狀況，利用放射治療或其他藥物，藉由增加免疫系統辨識癌細胞能力而增加肺癌臨床免疫治療效果。

獲獎榮譽

1.  2024年Advance in Digestive Medicine最佳優秀論文獎第二名。(Ai-Sheng Ho, Chun-Chia Cheng, Cheng-Liang Peng, Zong-Lin Sie, Chun Yeh, and Shou-Dong Lee.  論文名稱：STAT3 mediates cancer stem-like tumorsphere formation and PD-L1 expression to contribute radioresistance in HBV-positive hepatocellular carcinoma. Advance in Digestive medicine. 2024;1-11.)

2.  2022年擔任共同主持人執行原子能科技學術合作計畫MOST111-2623-E-182-003-NU「放射治療與CRISPR基因編輯活化免疫並應用於腫瘤核醫造影的技術建立」，獲優良計畫獎

3.  2022年長庚大學放射研究院研究獎

4.  2021年長庚大學放射研究院研究獎

學術會員

學術著作

• Chun-I Wang, Cheng-Yi Chen, Ting-Wen Chen, Chun-Chia Cheng, Shu-Wen Hong, Tsung-You Tsai and Kai-Ping Chang. PSMA2 promotes chemo- and radioresistance of oral squamous cell carcinoma by modulating mitophagy pathway. 2025. Cell Death Discovery. 11:2. (SCI/IF: 6.1).
  
• Ai-Sheng Ho, Jungshan Chang, Shou-Dong Lee, Zong-Lin Sie, Hui-Fen Shih, Chun Yeh, Cheng-Liang Peng, Kapil Dev, Chun-Chia Cheng*. Nucleos(t)ide analogues potentially activate T lymphocytes through inducing interferon expression in hepatic cells and patients with chronic hepatitis B. Scientific Reports. 2024. 14, 25286. *Corresponding author. (SCI/IF: 3.8)
  
• Sonjid Ochirbat, Tzu‑Chun Kan, Chun‑Chun Hsu, Tzu‑Hsuan Huang, Kuo‑Hsiang Chuang, Michael Chen, Chun‑Chia Cheng, Chun‑Chao Chang, Sri Rahayu, Jungshan Chang. The angiogenic role of the alpha 9‑nicotinic acetylcholine receptor in triple‑negative breast cancers. Angiogenesis. 2024. 27(4):827-843. (SCI/IF: 9.2).
• Chun-Chia Cheng, Jungshan Chang, Ai-Sheng Ho, Zong-Lin Sie, Cheng-Liang Peng, Chih‑Liang Wang, Kapil Dev, Chun-Chao Chang. Tumor-intrinsic IFNα and CXCL10 are critical for immunotherapeutic efficacy by recruiting and activating T lymphocytes in tumor microenvironment. Cancer Immunology Immunotherapy. 2024, 73; 175. (SCI/IF: 4.6).
• Chih‑Liang Wang, Ai‑Sheng Ho, Chun‑Chao Chang, Zong‑Lin Sie, Cheng‑Liang Peng, Jungshan Chang, Chun‑Chia Cheng*. Radiotherapy enhances CXCR3highCD8+ T cell activation through inducing IFNγ‑mediated CXCL10 and ICAM‑1 expression in lung cancer cells. Cancer Immunology Immunotherapy. 2023, 72(6);1865-1880. *Corresponding author. (SCI/IF: 5.8).
• Wei‑Chen Yen, Kai‑Ping Chang, Cheng‑Yi Chen, Yenlin Huang, Ting‑Wen Chen, Hsing‑Wen Cheng, Jui‑Shan Yi, Chun‑Chia Cheng, Chih‑Ching Wu and Chun‑I Wang. MFI2 upregulation promotes malignant progression through EGF/FAK signaling in oral cavity squamous cell carcinoma. Cancer Cell International (2023) 23:112. (SCI/IF: 5.8).
• Chun-Chia Cheng, Ai-Sheng Ho*, Cheng-Liang Peng, Jungshan Chang, Zong-Lin Sie, Yi-Li Chen, Cheng-Yi Chen*. Sorafenib suppresses radioresistance and synergizes radiotherapy-mediated CD8⁺ T cell activation to eradicate hepatocellular carcinoma. International Immunopharmacology. 2022, 27;112. (SCI/IF: 5.6).
• Ajnai G, Cheng CC, Kan TC, Lu JW, Rahayu S, Chiu A, Chang J. Improving Tirapazamine (TPZ) to Target and Eradicate Hypoxia Tumors by Gold Nanoparticle Carriers. Pharmaceutics. 2022 Apr 12;14(4):847.
• Kan TC, Lin MH, Cheng CC, Lu JW, Sheu MT, Ho YS, Rahayu S, Chang J. Preclinical Therapeutic Assessment of a New Chemotherapeutics [Dichloro(4,4'-Bis(2,2,3,3-Tetrafluoropropoxy) Methyl)-2,2'-Bipryridine) Platinum] in an Orthotopic Patient-Derived Xenograft Model of Triple-Negative Breast Cancers. Pharmaceutics. 2022 Apr 11;14(4):839.
• Chun-Chia Cheng, Yi-Fang Chang, Ai-Sheng Ho, Zong-Lin Sie, Jungshan Chang, Cheng-Liang Peng, and Chun-Chao Chang. Irradiation mediates IFNα and CXCL9 expression in non-small cell lung cancer to stimulate CD8⁺ T cells activity and migration toward tumors. Biomedicines. 2021, 9(10), 1349. (SCI/IF: 6.08)
• Chun-I Wang, Yi-Fang Chang, Zong-Lin Sie, Ai-Sheng Ho, Jungshan Chang, Cheng-Liang Peng and Chun-Chia Cheng*. Irradiation Suppresses IFNγ-Mediated PD-L1 and MCL1 Expression in EGFR-Positive Lung Cancer to Augment CD8⁺ T Cells Cytotoxicity. Cells. 2021, 10(10), 2515. *Corresponding author. (SCI/IF: 6.6)
• Ting‐Wen Chen, Kai‐Ping Chang, Chun‐Chia Cheng, Cheng‐Yi Chen, Shu‐Wen Hong, Zong‐Lin Sie, Hsing‐Wen Cheng, Wei‐Chen Yen, Yenlin Huang, Shu‐Chen Liu, and Chun‐I Wang. Characterization of recurrent relevant genes reveals a novel role of rpl36a in radioresistant oral squamous cell carcinoma. Cancers 2021, 13, 5623. (SCI/IF: 6.639)
• Chun-Chia Cheng, Hsin-Chi Lin, Ya-Wen Chiang, Jungshan Chang, Zong-Lin Sie, Bi-Ling Yang, Ken-Hong Lim, MD, Cheng-Liang Peng, Ai-Sheng Ho, Yi-Fang Chang. Nicotine exhausts CD8⁺ T cells against tumor cells through increasing miR-629-5p to repress IL2RB-mediated granzyme B expression. Cancer Immunology, Immunotherapy. 2021, 70(5):1351-1364. (SCI/IF: 6.968)
• Szu-YuanWu, Wan-Yu Yang, Chun-Chia Cheng, Kuan-Hao Lin, Bonifasius Putera Sampurna, Suat-Ming Chan, Chiou-Hwa Yuh. Low molecular weight fucoidan inhibits hepatocarcinogenesis and nonalcoholic fatty liver disease in zebrafish via ASGR/STAT3/HNF4A signaling. Clinical and Translational Medicine. 2020, 10(8):e252. (SCI/IF: 11.492)
• Chun-Chia Cheng, Bi-Ling Yang, Wen-Chao Chen, Ai-Sheng Ho, Zong-Lin Sie, Hsin-Chi Lin and Chun-Chao Chang. STAT3 Mediated miR-30a-5p Inhibition Enhances Proliferation and Inhibits Apoptosis in Colorectal Cancer Cells. International Journal of Molecular Sciences. 2020, 21:7315. (SCI/IF: 5.923)
• Szu-Yuan Wu, Wan-Yu Yang, Chun-Chia Cheng, Ming-Chen Hsiao, Shin-Lin Tsai, Hua-Kuo Lin, Kuan-Hao Lin, and Chiou-Hwa Yuh. Low molecular weight Fucoidan prevents radiation induced fibrosis and secondary tumors in a zebrafish model. Cancers. 2020, 12:1608. (SCI/IF: 6.639)
• Chun-Chia Cheng, Wan-Yu Yang, Ming-Chen Hsiao, Kuan-Hao Lin, Hao-Wei Lee, and Chiou-Hwa Yuh. Transcriptomically Revealed Oligo-Fucoidan Enhances the Immune System and Protects Hepatocytes via the ASGPR/STAT3/HNF4A Axis. Biomolecules. 2020, 10:898. (SCI/IF: 4.879)
• Chun-Chia Cheng, Po-Jui Hsu, Zong-Lin Sie, Fang-Hsin Chen. Discovery of Driver Genes in Colorectal HT29-derived Cancer Stem-Like Tumorspheres. JoVE Journal of Visualized Experiments. 2020, e61077. (SCI/IF: 1.355)
• Yi-Fang Chang, Ken-Hong Lim, Ya-Wen Chiang, Zong-Lin Sie, Jungshan Chang, Ai-Sheng Ho, Chun-Chia Cheng*. STAT3 Induces G9a to Exacerbate HER3 Expression for the Survival of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in Lung Cancers. BMC Cancer. 2019, 19:959. *Corresponding author. (SCI/IF: 3.150)
• Chun-Chia Cheng, Hsin-Chi Lin, Kaun-Jer Tsai, Ya-Wen Chiang, Ken-Hong Lim, Caleb Gon-Shen Chen, Ying-Wen Su, Cheng-Liang Peng, Ai-Sheng Ho, Ling Huang, Yu-Cheng Chang, Huan-Chau Lin, Jungshan Chang, Yi-Fang Chang. Epidermal growth factor induces STAT1 expression to exacerbate the IFNr-mediated PD-L1 axis in epidermal growth factor receptor-positive cancers. Molecular Carcinogenesis. 2018;57:1588-1598. DOI: 10.1002/mc.22881. (SCI/IF: 3.851/28.4%)
• Chun-Chia Cheng, Po-Nien Liao, Ai-Sheng Ho, Ken-Hong Lim, Jungshan Chang, Ying-Wen Su, Caleb Gon-Shen Chen, Ya-Wen Chiang, Bi-Ling Yang, Huan-Chau Lin, Yu-Cheng Chang, Chun-Chao Chang, Yi-Fang Chang. STAT3 exacerbates survival of cancer stem-like tumorspheres in EGFR-positive colorectal cancers: RNAseq analysis and therapeutic screening. Journal of Biomedical Science. 2018, 25:60. (SCI/IF:3.466/34.5%)
• Chun-Chia Cheng, Kuei-Fang Chou, Cheng-Wen Wu, Nai-Wen Su, Cheng-Liang Peng, Ying-Wen Su, Jungshan Chang, Ai-Sheng Ho, Huan-Chau Lin, Caleb Gon-Shen Chen, Bi-Ling Yang, Yu-Cheng Chang, Ya-Wen Chiang, Ken-Hong Lim, Yi-Fang Chang. EGFR-mediated interleukin enhancer-binding factor 3 contributes to formation and survival of cancer stem-like tumorspheres as a therapeutic target against EGFR-positive non-small cell lung cancer. Lung Cancer. 2018, 116: 80-89. (SCI/IF:4.294/18.6%)
• Cheng-Liang Peng, Hua-Ching Lin, Wei-Lun Chiang, Ying-Hsia Shih, Ping-Fang Chiang, Tsai-Yueh Luo, Chun-Chia Cheng, Ming-Jium Shieh. Anti-angiogenic treatment (Bevacizumab) improves the responsiveness of photodynamic therapy in colorectal cancer. Photodiagnosis and Photodynamic Therapy. 2018, 23: 111–118. (SCI/IF:2.895/57.2%)
• Chun-Chia Cheng, Jungshan Chang, Stanley Ching-Cheng Huang, Huan-Chau Lin, Ai-Sheng Ho, Ken-Hong Lim, Chun-Chao Chang, Ling Huang, Yu-Cheng Chang, Yi-Fang Chang*, Cheng-Wen Wu* YM155 as an inhibitor of cancer stemness simultaneously inhibits autophosphorylation of epidermal growth factor receptor and G9a-mediated stemness in lung cancer cells. PLoS One. 2017, 12(8): e0182149. (SCI IF:2.806/23.4%)
• Yu-Cheng Chang, Huan-Chau Lin, Yi-Hao Chiang, Caleb Gon-Shen Chen, Ling Huang, Wei-Ting Wang, Chun-Chia Cheng, Johnson Lin, Yi-Fang Chang, Ming-Chih Chang, Ruey-Kuen Hsieh, Shu-Jen Chen, Ken-Hong Lim, Yuan-Yeh Kuo. Targeted next-generation sequencing identified novel mutations in triple-negative myeloproliferative neoplasms. Med Oncol. 2017, 34: 83. (SCI/IF:2.634/58.1%)
• Bin-Bin Shih, Yi-Fang Chang, Chun-Chia Cheng, Hao-Jhih Yang, Kang-Wei Chang, Ai-Sheng Ho, Hua-Ching Lin, Chun Yeh, Chun-Chao Chang. SPECT Imaging Evaluation of ¹¹¹Indium-chelated Cetuximab for Diagnosing EGFR-Positive Tumor in an HCT-15-Induced Colorectal Xenograft. Journal of the Chinese Medical Association. 2017, 80: 766-773. (SCI/IF:1.252/52.9%)
• Cheng CC, Guan SS, Hao-Jhih Yang, Chang CC, Liao TZ, Chang J, Ho AS: Blocking heme oxygenase-1 by zinc protoporphyrin reduces tumor hypoxia-mediated VEGF release and inhibits tumor angiogenesis as a potential therapeutic agent against colorectal cancer. J Biomed Sci 2016, 23:18. (SCI/IF:2.799/39.8%)
• Wu JY, Cheng CC, Wang JY, Wu DC, Hsieh JS, Lee SC, Wang WM: Discovery of tumor markers for gastric cancer by proteomics. PloS one 2014, 9(1):e84158. (SCI/IF:2.806/23.4%)
• Cheng CC, Huang CF, Ho AS, Peng CL, Chang CC, Mai FD, Chen LY, Luo TY, Chang J: Novel targeted nuclear imaging agent for gastric cancer diagnosis: glucose-regulated protein 78 binding peptide-guided (111)In-labeled polymeric micelles. Int J Nanomedicine 2013, 8:1385-1391. (SCI/IF:4.3/14.4%)
• Cheng CC, Lu N, Peng CL, Chang CC, Mai FD, Chen LY, Liao MH, Wang WM, Chang J: Targeting to overexpressed glucose-regulated protein 78 in gastric cancer discovered by 2D DIGE improves the diagnostic and therapeutic efficacy of micelles-mediated system. Proteomics 2012, 12(15-16):2584-2597. (SCI/IF:4.041/19.2%)
• Cheng CC, Chang J, Chen LY, Ho AS, Huang KJ, Lee SC, Mai FD, Chang CC: Human neutrophil peptides 1-3 as gastric cancer tissue markers measured by MALDI-imaging mass spectrometry: Implications for infiltrated neutrophils as a tumor target. Dis Markers 2012, 32(1):21-31. (SCI/IF:2.348/39.2%)
• Liu SL, Cheng CC, Chang CC, Mai FD, Wang CC, Lee SC, Ho AS, Chen LY, Chang J: Discovery of serum biomarkers of alcoholic fatty liver in a rodent model: C-reactive protein. J Biomed Sci 2011, 18:52. (SCI/IF:2.799/39.8%)
• Ho AS*, Cheng CC*, Lee SC, Liu ML, Lee JY, Wang WM, Wang CC: Novel biomarkers predict liver fibrosis in hepatitis C patients: alpha 2 macroglobulin, vitamin D binding protein and apolipoprotein AI. J Biomed Sci 2010, 17:58. (*equal contribution) (SCI/IF:2.799/39.8%)
• Kuo WW, Kuo HW, Cheng CC, Lai HL, Chen LY: Roles of the minor pseudopilins, XpsH, XpsI and XpsJ, in the formation of XpsG-containing pseudopilus in Xanthomonas campestris pv. campestris. J Biomed Sci 2005, 12(4):587-599. (SCI/IF:2.799/39.8%)

歷年計畫主持人研究計畫