摘要:不同的病人基於個體及基因的差異,必須應用不同的治療方式、藥物或療程,來達到最適的治療效果。為了達到精準醫學,我們必須對各種疾病在形成機制上有更清楚的瞭解,才能提出更好的治療策略。本計畫將運用數種體學的方法,經由深入了解多種癌症,感染症及逆境醫學三大未滿足的疾病,對這些疾病治療上提出更有效的療程、策略或方法,以應付疾病原因在個體及種族的差異。本研究中心將藉由既有多體學資源,結合資訊與結構生物學專業,組成此團體科學合作平台。 全球的快速交流,以及氣候變遷,我們仍面對著新興或重來傳染病的威脅,臺大醫學院未來希望根除重來或原有的傳染病,也將研究微生物菌叢與人類健康之關係。粒線體是生物逆境壓力之檢測器,我們將檢驗粒線體動態及了解粒線體逆境反應。逆境醫學的研究也將提供癌症團隊在發展新的癌症標記及建立標記新療法的理論基礎。免疫療法為尖端的癌症研究,但僅有5-30%病人有療效。我們將分析肝癌、胃癌及肺癌病人的腫瘤檢體突變的基因及用多重分析法直接尋找有療效這群T細胞株,目前團隊蒐集病人癌組織、附近免疫組織及周邊血液,針對有療效的病人做分析,進而應用這些癌症,感染症及逆境醫學研究獲得之資訊達到精準醫學的目標。
Abstract: Due to genetic and personal variances, patients are treated by different therapeutic approaches to obtain the best outcome. To reach precision medicine for clinical unmet need, we must have a clearer picture in basic knowledge of diseases. Our center will utilize multiple omic approaches to understand in depth the mechanisms of three clinical unmet need diseases: infectious diseases, stress medicine and cancers. These studies will provide more efficient therapeutic approaches to cope with racial and personal differences. Based on the resources in omics of our center, we will combine with expertise of informatics and structural biology to form a strong group to answer these questions. Owing to rapid interflow and climate change worldwide, we still face the challenge of threat of emerging and reemerging infectious diseases. We will develop new therapeutic methods to irradiate the reemerging and old infectious diseases. Moreover, not all infectious microbes are pathogenic. Human commensal microbes may participate in and alter development, immune maturation, disease formation and treatment outcome. Therefore, we will also study function of microbiota. Overloaded stress can be pathogenic in different diseases. Mitochondrion is a stress sensor in eukaryotes. We will establish new image systems coupled with omic approaches to integrate mitochondria responses to different stresses. The identified signal pathways can provide new biomarkers for prediction/prevention and targets for treatment. Furthermore, alterations in mitochondrial signals that affect the genome stability of cells and the interplay between microenvironment and immune system will be accessed for their contribution to cancer progression and therapeutic response. Hence, basic research in stress medicine will harness the exploration towards new markers and therapeutic design for diseases involving mitochondrial alterations. Microenvironment of cancers, especially the interplay with the immune system, plays the key role in cancer progression and drug resistance. Given that only a small fraction of patients display positive response to immunotherapy, using novel biomarker to select right patient for treatment is of vital importance. We will collect patients’ cancer tissues, nearby immunological tissues and bloods, characterize immune microenvironment including the subtypes and spacial distribution of T cells or other immune cells, and analyze mutation pattern of tumor cells and correlate to outcome of immunotherapy. Liver, head and neck and lung cancers will be focused. We will also use patients’ samples to examine their mutated genes and match T cell receptors isolated from single cell sorting. Cancer Hospital will link the whole NTU system to cultivate medical leaders and research elites to dissect the cause of diseases and solve the current difficulty in clinical therapy. We will take charge in genotyping, marker hunting, diagnosis advance, medical device and drug development. We will collaborate with related corporations and government organizations to train clinical experts, high level researchers and leaders. Our center currently executes SPARK program. We will train members in other universities or industrial companies. Our omic platform will connect not only the whole research systems in multi-disciplinal field of NTU, but also resources in corporations and government organizations in the Biotechnique Parks, to assist Taiwan to train talent elites.