Dr. Mou, Yun 牟昀 博士

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Dr. Mou, Yun
牟昀 博士

Assistant Research Fellow
助研究員

    • B.S. National Taiwan University
    • M.S. National Taiwan University
    • Ph.D. California Institute of Technology
    • Postdoc. University of California, San Francisco
  • 2789-9035 (Lab) (Room No: N721)
  • 2652-3009 (Office)
  • ymou@ibms.sinica.edu.tw
Specialty:
  • Computational protein design
  • Antibody engineering
  • Immunotherapy
  • Cancer proteomics
  • CRISPR screening

RESEARCH

Our laboratory devotes on developing genetically engineerable biologics for cancer therapy, especially immunotherapy. We focus on four types of therapeutic biologics: proteins, virus (gene therapy), bio-nanoparticles, and bacteria. For protein therapy, we employed state-of-the-art techniques, including computational protein design, directed evolution, phage/yeast display, to improve the properties of anti-tumor proteins, such as antibodies/nanobodies, cytokines, CRISPR/Cas proteins, etc. For virus-based gene therapy, we develop novel vehicles by deep engineering of bacteriophage. Bacteriophage has several advantages over the traditional human virus for gene therapy, including cheap production, high yield, and designed tropism to human cells. For bio-nanoparticle therapy, we utilize the outer membrane vesicles (OMVs), which is a highly immunogenic nanoparticle generated by bacteria. OMVs show great tumor-targeting ability and anti-tumor activity, and can be genetically modified by plasmid transformation. For bacterial therapy, several bacteria, including E. coli, can target and colonize in tumors. We exploit bacteria as a live factory for constantly secreting therapeutic payloads into tumor microenvironment.       

We have successfully achieved complete remission in murine tumor models using several modalities of our therapies. While continuously improving our drug designs, we will expand our endeavors to more tumor models in mice and potentially other high mammals.    

研究介紹

本實驗室目前專注於開發可應用於癌症療法的基因改造工程技術及藥物,來誘發人體免疫反應以對抗腫瘤細胞生長(免疫療法)。我們發展四種不同材料的生物製劑—蛋白質、病毒(基因療法)、生物奈米顆粒、及細菌—來對癌症做治療:
(一) 新型蛋白質療法:我們藉由最新穎的技術—電腦模擬計算設計、定向進化蛋白質工程、嗜菌體/酵母菌呈現系統—製造出改良的抗體/奈米抗體、細胞激素、CRISPR/Cas9 等蛋白質,以期達到更佳的療效。
(二) 病毒為載體的基因療法:我們開發利用嗜菌體做為基因療法的載體,可達到低成本、高產量、同時可設計針對特定細胞進行感染的優點。
(三) 生物奈米顆粒:經細菌產生出的奈米顆粒—外膜囊泡 (Outer membrane vesicles)—對腫瘤組織有極佳的標靶能力,且具有高度免疫激發性及抗腫瘤活性。細菌外膜囊泡可藉由簡單的質體轉形達到對奈米顆粒的修飾以此增加其療效。
(四) 細菌療法:文獻上已知有一些品系的細菌(包含大腸桿菌)可選擇性地於腫瘤組織進行共生。我們利用此一特性使改造過的細菌成為活體工廠,持續性地於腫瘤組織分泌具抗腫瘤活性的分子。

實驗室至今已成功利用以上數種療法將小鼠生長的腫瘤完全治癒。未來將持續改良我們的藥物設計,應用在更多的小鼠腫瘤模型中或是更高等的哺乳動物。

HIGHLIGHT 重要成果

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