研究興趣
Research Interest
本實驗室致力於開發針對抗藥性細菌的新型抗菌藥物與生醫材料，融合微生物學、藥物研發、材料科學與再生醫學技術。我們的研究包含但不限於以下數個主題：
1) 淋病雙球菌致病機轉
2) 超靈敏ELISA偵測方法開發
3) 抗菌新藥/療法開發
4) 多功能組織工程再生材料開發
除一般研究以外，轉譯醫學也是實驗室重點之一，即如何將自己所研究的內容轉為實質用途而非紙上談兵，包含新藥/醫材法規與商業模式啟發等。我們期望透過這些創新技術，能夠為臨床提供突破性的解決方案。
The Innovative Antimicrobials & Biomaterials Lab (IAB Lab) is dedicated to developing novel antimicrobial drugs and biomaterials against drug-resistant pathogens, integrating microbiology, drug and biomaterial development, materials science, and regenerative medicine technologies.
Our research encompasses, but is not limited to, the following topics:
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Pathogenesis of Neisseria gonorrhoeae;
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Development of ultra-sensitive ELISA detection methods;
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Discovery of new antimicrobial agents;
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Multifunctional biomaterials for tissue regeneration.
Beyond fundamental research, translational medicine is also one of our key focuses, as we aim to translate laboratory findings into practical applications, including insights into drug/medical device regulations and potential business models. Through these innovative approaches, we aspire to deliver breakthrough solutions for clinical medicine.
淋病雙球菌致病機轉 Pathogenesis of Neisseria gonorrhoeae
奈瑟氏淋病雙球菌(Neisseria gonorrhoeae，GC)是一種常見的性傳染致病菌，引發淋病，為一種局部感染 (localized infection)，然而若治療不當或高致病力菌株感染時，則可能由局部感染侵襲導致全身性/瀰漫性淋病感染 (disseminated gonococcal infection，DGI)。過去文獻已報導當GC由上皮細胞外移行 (transmigration)至上皮細胞下的過程中，觀察到減少Opa、pili等表面抗原表現量顯著低下，然而調節這些蛋白表現或抗原脫去的相關調節因子仍然不明。
Neisseria gonorrhoeae (GC) is a major sexually transmitted pathogen causing gonorrhea, typically a localized infection. However, without appropriate treatment or in cases of highly virulent strains, GC can lead to disseminated gonococcal infection (DGI). Previous studies have reported that during GC transmigration across epithelial cells, the expression of surface antigens such as Opa proteins and pili is markedly reduced. Nevertheless, the regulatory factors controlling antigen expression or shedding remain poorly understood. Our work aims to elucidate the molecular mechanisms underlying these pathogenic processes.
(Nature Reviews Microbiology volume 16, pages226–240 (2018))
超靈敏ELISA偵測方法開發Development of Ultra-Sensitive ELISA (uELISA)
超靈敏酵素免疫分析技術（Ultra-Sensitive Enzyme-Linked Immunosorbent Assay, uELISA）是一種突破傳統ELISA偵測極限的創新技術，具有高度靈敏度與低背景干擾，能夠準確測定極低濃度的生物標誌物，利用thio-NAD及3α-HSD酵素的循環反應，將原ELISA反應的單一訊號放大為數個，以達到uELISA的目標，可實現低於10⁻¹³ M的檢測極限，意即在100 μL的檢測反應中，能夠偵測到低至10⁻¹⁷ mole的目標抗原，使其成為精準醫學領域中極具潛力的高靈敏度分析工具。
本方法為與日本早稻田大學 伊藤 悅朗教授自2022年初即開始聯繫並進行研究交流，並於2022年6月起受聘為訪問學者，於同年10月正式赴早稻田大學進行研究訪問，迄今仍與伊藤教授為合作關係，開發不同精準超靈敏檢測方法，積極安排教育部學海築夢計畫學生的選送 (已完成執行113、114年選送計畫)，並讓學生可以到日本早稻田大學實習一個月。
Ultra-Sensitive Enzyme-Linked Immunosorbent Assay (uELISA) is an innovative technology that surpasses the detection limits of conventional ELISA. By employing a thio-NAD and 3α-HSD enzyme cycling system, uELISA amplifies single reaction signals into multiple outputs, achieving a detection limit as low as 10⁻¹³ M. This allows the detection of target antigens at concentrations down to 10⁻¹⁷ mole in a 100 μL assay, making uELISA a highly promising tool for precision medicine.
This project was initiated in collaboration with Professor Etsuro ITO at Waseda University in 2022. I’m appointed as a visiting scholar at Waseda from June 2022 and began collaborative research in the same year. The partnership continues to focus on developing novel high-sensitivity detection strategies and training students through academic exchange programs such as Taiwan’s Ministry of Education MOE Overseas Study Project for Internships.
(Journal of Clinical Medicine (JCM) 10(21):5197)
抗菌新藥/療法開發Discovery of new antimicrobial agents
臨床微生物感染多仰賴抗生素或抗菌製劑的治療，雖藥物療效極佳，但常也伴隨著抗藥性微生物的問題，其中包含碳青黴素抗藥性革蘭氏陰性細菌、甲氧西林抗藥性金黃色葡萄球菌、萬古黴素抗藥性腸球菌、喹諾酮抗藥性淋病雙球菌、Azole類抗藥性黴菌等。因此實驗室研究中，由天然物萃取物、萃取物衍生物、小分子藥物、胜肽藥物或FDA認證藥物老藥新用等方式篩選具有潛力的抗菌新藥，並藉由完整的藥物評估流程，包含體外試驗與體內試驗 (使用秀麗隱桿線蟲或小鼠感染模式)，驗證藥物的抗菌效果與開發潛力，希冀可透過我們的研究讓臨床抗藥性微生物問題得到緩解。
2020年以新興抗生素開發項目—碲造生機於FITI與U-Start兩大創新創業計畫最高殿堂中獲獎，並設立嘉登生技有限公司 (2020-2022)。
The treatment of microbial infections largely relies on antibiotics and antimicrobial agents. However, the emergence of resistant pathogens—including carbapenem-resistant Gram-negative bacteria, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), fluoroquinolone-resistant N. gonorrhoeae, and azole-resistant fungi—poses a global health crisis.
Our lab investigates novel antimicrobial candidates derived from natural extracts, derivatives, small molecules, peptides, and repurposed FDA-approved drugs. Potential compounds undergo comprehensive evaluation, including in vitro testing and in vivo infection models (e.g., Caenorhabditis elegans and murine models), to validate antimicrobial efficacy and translational potential.
In 2020, our antibiotic development project “Tellurium containing compound” was awarded at Taiwan’s FITI and U-Start innovation programs, leading to the establishment of Garden Biotech Co., Ltd. (2020–2022).
多功能組織工程再生材料開發
Multifunctional biomaterials for tissue regeneration
齲齒相關疾病是全球性健康問題，尤其在國內龋齒治療的臨床需求高漲，而傳統活髓治療材料無法完全滿足抗菌性及促進組織再生的需求。活髓治療 (Vital Pulp Therapy，VPT)是牙髓再生領域中的一個重要方法，其目的是保存並維持因齲齒、外傷、或醫源性因素而受損但未完全破壞的牙髓組織。隨著組織工程的發展，生物材料成為活髓治療的重要研究方向。理想的牙髓覆蓋/覆髓材料需要能有效促進修復性牙本質的形成，維持牙髓的活性，同時具備良好的抗菌性能。成功合成並研發載銀銅雙金屬生物介孔生物活性玻璃材料 (AgCu/80S)，並觀察到其對於人類牙髓幹細胞 (human dental pulp stem cell，hDPSC)具有誘導分化、促進礦化沉積的能力；對於人類臍靜脈內皮細胞 (Human umbilical vein endothelial cell，HUVEC)具有促移行 (migration)與tube formation的能力；對於糞腸球菌 (Enterococcus faecalis)具有抗菌能力。
Dental caries remains a global health challenge, with significant unmet needs for biomaterials that provide both antimicrobial effects and regenerative potential in vital pulp therapy (VPT). VPT aims to preserve pulp vitality in cases of caries, trauma, or iatrogenic injury. With advances in tissue engineering, bioactive materials are emerging as crucial candidates for pulp regeneration.
An ideal pulp-capping material should promote reparative dentin formation, maintain pulp vitality, and exhibit strong antimicrobial activity. Our lab successfully synthesized a silver–copper co-doped mesoporous bioactive glass (AgCu/80S), which demonstrated:
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Differentiation and mineralization induction in human dental pulp stem cells (hDPSCs).
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Enhanced migration and tube formation in human umbilical vein endothelial cells (HUVECs).
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Potent antibacterial activity against Enterococcus faecalis.
These multifunctional materials show promise in advancing both infection control and regenerative dentistry.
(Collaborate with KMU Dr. Shih and Dr. Kung)