生物醫學研究所

研究方向及研究室特色

研究主軸一：Cathepsin S 與腫瘤免疫調控

探討 Cathepsin S（CTSS）如何調控蛋白質穩定性與後轉譯修飾，影響抗原呈現、免疫檢查點表達及腫瘤免疫微環境。整合蛋白質體學、多重免疫螢光與多體學分析，系統性解析 CTSS 與免疫細胞浸潤的關聯，評估其作為預測 PD-1/PD-L1 抑制劑治療反應之生物標記潛力，為頭頸癌免疫治療提供新靶點。

研究主軸二：Cathepsin S 抑制劑與奈米藥物開發應用於精準癌症治療

開發新型 CTSS 抑制劑與腫瘤微環境響應性奈米載體，提升藥物專一性、穩定性與腫瘤累積濃度，減少脫靶毒性。結合電腦輔助藥物設計優化抑制劑，評估與免疫檢查點抑制劑的協同療效，整合動物模型與臨床資料尋找預測性生物標記，建立基礎到臨床的完整轉譯平台。

研究主軸三：色氨酸代謝與癌症免疫治療

與成功大學及國際頂尖大學合作，開發新型色氨酸代謝抑制劑，聚焦 IDO1–kynurenine 路徑在免疫抑制中的角色。篩選出同時抑制 IDO1 與 ABCB1（P-gp）的候選藥物，雙靶點策略可逆轉免疫抑制並克服未來抗藥性，提升免疫治療效果並降低復發風險。

研究主軸四：Cathepsin S 與癌症轉移

探討 CTSS 如何降解細胞外基質並調控 EMT 訊號，促進癌細胞侵襲與遠端轉移。利用尾靜脈注射與原位移植動物模型，解析 CTSS 對循環腫瘤細胞存活、血管新生及器官定殖的影響，評估 CTSS 抑制劑作為抗轉移治療策略的潛力，為晚期癌症患者提供新型治療選項。

最近五年所發表論文: (*, Corresponding author):

      1. Chen PC, Chang YC, Ho YY, Tseng KY, Lin KH, Sari S, Özdemir Z, Reynisson J, Leung E, Cheung CHA*. Discovery of a novel miconazole analogue as a dual apo-IDO1 inhibitor and ABCB1 modulator for cancer immunotherapy and chemosensitizing. European Journal of Pharmaceutical Sciences (2026) 224, 107605 (Impact Factor: 5.1; Ranking: Pharmacology & pharmacy 65/356 (Q1)) (co-first author)
2. Chang YC, Huang WL, Su WC, Cheng FY, Cheung CHA*. BIRC5 promoter-driven nanodrugs suppress BIRC5-positive cancers independent of ABCB1 status. International Journal of Nanomedicine (2026) 21:588571 (Impact Factor: 8.7; Ranking: Pharmacology & pharmacy 17/356 (Q1))
3. Liu CC, Wu CL, Wang CY, Lee JS, Chen PY, Anuraga G, Solomon DD, Qiu LY, Chang YC, Chu JM, Huang CY, Chuang JY, and Chang KY*. Tumor-derived RPS19 engages C5AR1+inflammatory macrophages to drive astrocyte reprogramming and glioblastoma progression. Cell Communication and Signaling. (2026) (Impact Factor: 11.6; Ranking: Cell biology 29/207 (Q1)) 
4. Lin YC, Lin TY, Chang YC, Cheng HC, Hong YK, Aala WJH, Reyes HH, Hou PC, Huang HY, Guevara BEK, Cheung CHA, McGrath JA, Hsu CK*. Synergistic Enhancement of PD-L1 Expression from DNA Repair Dysfunction and UV Exposure in Xeroderma Pigmentosum: Potential Therapeutic Role of PD-L1 Inhibitors. Journal of Dermatological Science. (2026) (Impact Factor: 4.6; Ranking: Dermatology 11/99 (Q1))
5. Chang YC, Chen SJ, Chen SH, Hsiao SY, Chen LH, Chen CH, Liu CC, Chen YW, Liu KJ, Wu SY, Chu JM, Qiu LY, Chiang WF, Hsieh HP, Hsueh WY, Hsiao JR, Shen MR, Chang JY*, and Chang KY*. Unraveling Cathepsin S Regulation in Interleukin-7-mediated Anti-tumor Immunity Reveals its Targeting Potential Against Oral Cancer. Journal of Biomedical Science (2025) 32:69 (Impact Factor: 14.5; Ranking: Medicine, research & experimental 8/191 (Q1)) 
6. Cheng SM, Chang YC, Lin TY, Leung E, Coumar MSC, Cheung CHA*. Did we miss something important? Rethinking the effects of autophagy and mitophagy on DNA damage repair and genomic stability. Journal of Cancer Metastasis and Treatment (2025) 11:16 (Impact Factor: 1.6; Ranking: Oncology 280/333 (Q4))
7. Peng HY, Chang KY, Chang WM, Wu CY, Lee HL, Chang YC, Liu KJ, Shiah SG, Kuo CC, Chang JY. EGFRvIII-driven microenvironmental fibroblast activation and transformation accelerate oral cancer progression via lipocalin-2/STAT3 axis. Neoplasia (2025) 66:101193((Impact Factor: 4.8; Ranking: Oncology 92/333 (Q2))
8. Lee CH, Lin YC, Chang YC, Chen OC, Lin KH, Yeh TM, Leung EY, Lin IL, Chen SH, Cheung CHA*. NUPR1 contributes to endocrine therapy resistance by modulating BIRC5 expression and inducing luminal B-ERBB2+ subtype-like characteristics in estrogen receptor-positive breast cancer cells. Journal of Cancer (2025) 16(5):1694-1708 (Impact Factor: 3.4; Ranking: Oncology 148/333 (Q2))
9. Liu CC, Yang WB, Chien CH, Wu CL, Chuang JY, Chen PY, Chu JM, Cheng SM, Qiu LY, Chang YC, Hwang DY, Hung CY, Lee JS, Chang KY*. CXCR7 activation evokes the anti-PD-L1 antibody against glioblastoma by remodeling CXCL12-mediated immunity. Cell Death and Disease (2024) 15(6):434 (Impact Factor: 12.2; Ranking: Cell biology 27/207 (Q1))
10. Lin IL, Lin YT, Chang, YC, Kondapuram SK, Lin KH, Chen PC, Kuo CY, Coumar MS, Cheung CHA*. The SMAC mimetic GDC-0152 us a direct ABCB1-ATPase activity modulator and BIRC5 expression suppressor in cancer cells. Toxicology and Applied Pharmacology (2024) 5:116888 (Impact Factor: 3.6; Ranking: Toxicology 35/106 (Q2))
11. Chang YC, Shieh MC, Chang YH, Huang WL, Su WC, Cheng FY, Cheung CHA*. Development of a cancer cells self-activating and miR-125a-5p expressing poly-pharmacological nanodrug for cancer treatment. International Journal of Molecular Medicine (2022). 50(2): 102 (Co-first author) (Impact Factor: 8.5; Ranking: Medicine, research & experimental 22/191 (Q1))
12. Chang YC, Cheung CHA*. An updated review of Smac mimetics, LCL161, Birinapant, and GDC- 0152 in cancer treatment. Applied Sciences (2021). 11(1), 335 (Impact Factor: 2.9; Ranking: Engineering, multidisciplinary 78/179 (Q2))
13. Cheng SM, Lin TY, Chang YC, Lin IW, Leung E and Cheung CHA*. YM155 and BIRC5 downregulation induce genomic instability via autophagy-mediated ROS production and inhibition in DNA repair. Pharmacological Research (2021). 166:105474 (Impact Factor: 12.2; Ranking: Pharmacology & pharmacy 4/356 (Q1))