腎臟纖維化是慢性腎臟疾病中常見且最終的病理表現，其形態學特徵包括腎小球硬化、腎小管萎縮、腎間質慢性發炎、纖維化及血管稀疏等。當腎損傷的修復過程失衡時，細胞外基質蛋白如纖連蛋白與膠原蛋白會過度累積，造成組織結構破壞與腎功能障礙，最終導致器官衰竭。本實驗室致力於設計與合成新穎小分子化合物，以減緩或抑制腎臟纖維化的進程。我們期望開發具臨床潛力的藥物，延緩腎功能衰退，並阻止腎衰竭及換腎的發生。

Renal fibrosis represents a common and terminal pathological outcome of chronic kidney disease, characterized by glomerulosclerosis, tubular atrophy, chronic interstitial inflammation, fibrosis, and vascular rarefaction. When the repair process following renal injury becomes dysregulated, extracellular matrix (ECM) proteins such as fibronectin and collagen accumulate excessively, leading to structural damage, functional impairment, and ultimately organ failure. Our laboratory is dedicated to designing and synthesizing innovative small‑molecule compounds to mitigate or inhibit the progression of renal fibrosis. We aim to develop clinically promising therapeutics that preserve renal function and prevent kidney failure or transplantation.

傳統抑制劑需持續與蛋白質的活性或變構位點結合，才能維持抑制效果，往往需要高劑量暴露。相較之下，靶向蛋白質降解（Targeted Protein Degradation, TPD）透過細胞內的蛋白質穩態機制，直接移除目標蛋白，使藥理作用延續至蛋白質重新合成之前。本實驗室設計、合成並評估新穎的 蛋白質降解嵌合體（PROteolysis TArgeting Chimera, PROTAC）效果，利用 泛素–蛋白酶體系統降解標靶蛋白。PROTAC 透過同時結合目標蛋白與 E3 泛素連接酶，促進目標蛋白泛素化並送入蛋白酶體降解。此策略為精準醫療提供新方向，期望能開發具臨床潛力的小分子藥物，用於治療各類疾病。Conventional inhibitors require continuous binding to active or allosteric sites on proteins to maintain suppression, often necessitating high systemic exposure. In contrast, Targeted Protein Degradation (TPD) harnesses cellular proteostasis pathways to eliminate the protein itself, allowing pharmacological effects to persist until new synthesis occurs. Our laboratory designs, synthesizes, and evaluates novel PROteolysis TArgeting Chimeras (PROTACs) that exploit the ubiquitin–proteasome system (UPS). PROTACs are bifunctional molecules that simultaneously engage the protein of interest and an E3 ubiquitin ligase, promoting ubiquitination and subsequent proteasomal degradation. This approach represents a promising avenue for precision therapeutics, aiming to develop clinically relevant small‑molecule degraders for diverse diseases.

免疫檢查點蛋白可透過調節或抑制免疫細胞活性來控制免疫系統反應。腫瘤免疫療法利用患者自體免疫系統清除癌細胞，近年最具代表性的策略即為免疫檢查點調控，例如使用抗 Programmed death‑1 (PD‑1) 抗體阻斷 T 細胞的免疫負調控機制，以提升其活性與辨識癌細胞的能力。 先前研究指出，雙標靶 MAO A/HSP90 抑制劑可有效抑制癌細胞生長並降低 PD‑L1 表現量。本實驗室進一步利用大腸癌與多形性膠質母細胞瘤的小鼠模型，評估抑制劑與免疫檢查點抑制劑併用的抗腫瘤效果，並分析小鼠體內不同免疫細胞族群的變化。 

Immune checkpoint proteins regulate immune cell activity to fine‑tune immune responses. Tumor immunotherapy leverages the patient’s own immune system to eradicate cancer cells, with immune checkpoint modulation—such as anti‑Programmed death‑1 (PD‑1) antibody therapy—emerging as a leading approach to enhance T‑cell activation and tumor recognition. Previous studies demonstrated that dual‑target MAO A/HSP90 inhibitors effectively suppress tumor growth and downregulate PD‑L1 expression. Our laboratory employs mouse models of colorectal cancer and glioblastoma to evaluate the combined therapeutic efficacy of these inhibitors with immune checkpoint blockade, further analyzing immune cell composition and dynamics within the tumor microenvironment.