Major focus of ISCTCR research


一、 研究方向：
following research focuses are being actively pursued in our Institute:
  1. Harnessing stem cell properties for regenerative medicine and development of stem cell-related theranostics
  2. Studies of tumor associated glycans and their biosynthetic enzymes that regulate tumor growth and tumor microenvironment and delineate the clinical relevance of their expression
  3. Immune modulatory activities of GSLs in immune mediated disorders and immune tolerance of pregnancy and their clinical implications
  4. Identification of novel molecular markers of cancer stem cells (CSCs) for theranostics applications
  5. Development of novel anti-cancer therapeutics using our patented universal CTP platform technologies
  6. Development of disease-derived iPSCs and genome editing
  7. Development of anti-tumor therapeutic strategies by harnessing innate killer immunity
二、 重點研究成果：
本所宗旨在於從事有關幹細胞與癌症的研究，藉由整合跨領域研究題材，積極與臨床醫師進行破壞性創新與實質影響的生醫研究。本所利用胚胎幹細胞與iPSC分化的技術平台，進行4項新穎的醫療研發，包括：
  1. 以iPSC分化肝細胞平台篩選可根除B型肝炎之藥物
  2. 以心臟病人iPSC分化為心臟細胞來篩選可治療之藥物
  3. 探討早期胚胎發育的醣質變化，可發展人工生殖醫學之臨床應用
  4. 利用獨特的NK細胞之大量培養技術，再結合單株抗體成為標靶NK細胞療法
同時，本所利用胚胎幹細胞與癌症幹細胞特殊的技術，找出多個新穎的磷酸蛋白、醣脂、與醣蛋白，進行另外4項創新的抗癌研發，包括：
  1. 發展全球第一個醣脂標靶抗癌藥物，並持續精進其他醣脂的抗癌應用
  2. 研發精準打擊癌細胞與癌症幹細胞的胜肽導彈，結合其他藥物發揮抗癌療效
  3. 發展全新可標靶癌症幹細胞之抗體，並發展為抗體藥物複合物
  4. 利用醣脂質轉化酵素在癌細胞之研究成果來進行臨床應用
三、 技術產出：
  1. 本所執行科技部價創計畫「以新穎癌症專一性的標靶胜肽為平台，建立適用於多種癌症兼可殲滅癌症幹細胞的新療法」開發相關產品技術包括FnCTP平台與FnCTP-BsAb、FnCTP-MNC-Herceptin兩項產品，並專屬授權予友生泰生醫股份有限公司。相關研發成果已申請美國專利。
  2. 本所與生技開發中心合作研發癌症幹細胞標靶分子TMCC3之單株抗體，獲得美國、歐盟、臺灣專利。
  3. 本所自行研發Puf-A shRNA可抑制或降低癌細胞生長，並獲得美國專利。
  4. 本所自行研發ST3Gal3下調之癌細胞株，可用於加速抗體之研發進度，已申請美國等多國專利。
  5. 本所自行研發LRRN1標靶抗體用於癌症治療、及運用LRRN1自體抗體搭配其他已知臨床標記物用於癌症診斷之方法，已申請美國、歐盟等多國專利。
四、 學術獎項與交流：
五、 跨中心及跨國合作：
  1. 科技部2017-2021再生醫學單一整合型計畫“開發具有幹細胞特性於再生醫學與腫瘤診治之應用”：主持人游正博特聘講座教授與陳鈴津院士、洪志宏醫師(林口長庚)、吳為吉醫師(林口長庚)、葉昭廷醫師(林口長庚)、張國軒醫師(林口長庚)、吳漢忠教授(中研院)、吳忠勳研究員(生技中心)共同合作。
  2. 衛福部2016-2021第3期癌症單一整合型計畫“整合台灣兒童癌症臨床治療及分子診斷”：主持人陳鈴津院士與高雄長庚病理科黃玄瀛醫師、高雄長庚兒童血腫科沈俊明醫師、蕭志誠醫師、台北馬偕劉希哲醫師、北醫附醫黃棣棟醫師、中山附醫巫康熙醫師、台大醫院盧孟佑醫師、國衛院黃秀芬醫師、中研院邱國平副研究員共同合作。
  3. NCI, USA: Dr. Ira Pastan, Co-Chief, Laboratory of Molecular Biology, Center for Cancer Research. “Development of cancer-targeting peptide-immunotoxin”, 2019~present.
  4. Children’s Oncology Group: Chair of multi-national clinical trial of immunotherapy of high risk neuroblastoma: COGANBL0032 (USA, Canada, New Zealand and Australia), 2014~present.
  5. OBI Pharma: Designed the ongoing multi-national phase II/III randomized clinical trial of Globo H vaccine in metastatic breast cancer (Taiwan, Hong Kong, Korea, USA, India), and served as the reference laboratory for immune monitoring of patients enrolled into this clinical trial, 2014~present.
  6. University of California San Diego, USA: Dr. Mitchell Diccianni, Project Scientist. “GD2-targeting immunotherapy”, 2014~present.
  7. University of Pennsylvania, USA: Dr. Carl June, Director of the Center for Cellular Immunotherapies. “Identification of glycolipids, development of glycan-targeting therapy and CAR-T”, 並協助接洽婦癌科湯雲心醫師至該中心進行三年訓練，未來將協助本院Cell Therapy Center發展, 2017~present.
六、 近兩年論文表現：
七、 近一年發表論文：
  1. Lin R.J., Kuo M.W., Yang B.C., Tsai H.H., Chen K., Huang J.R., Lee Y.S., Yu A.L., Yu J.* B3GALT5 knockout alters glycosphingolipid profile and facilitates transition to human naïve pluripotency. PNAS 2020, 117(44):27435-44.
  2. Chan Y.T., Lai A.C., Lin R.J., Wang Y.H., Wang Y.T., Chang W.W., Wu H.Y., Lin Y.J., Chang W.Y., Wu J.C., Yu J.C., Chen Y.J., Yu A.L.* GPER-induced signaling is essential for the survival of breast cancer stem cells. Int. J. Ca. 2020, 146(6): 1674-85.
  3. Yu J., Hung J.T., Wang S.H., Cheng J.Y., Yu A.L.* Targeting glycosphingolipids for cancer immunotherapy. FEBS Letters 2020, 594: 3602-18.
  4. Wang S.H., Wu T.J., Lee C.W., Yu J.* Dissecting the conformation of glycans and their interactions with proteins. J. Biomed. Sci. 2020, 27: 93.
  5. Wu K.S., Ho D.M., Jou S.T., Yu A.L., Tran H.M., Liang M.L., Chen H.H., Lee Y.Y., Chen Y.W., Lin S.C., Chang F.C., Tsai M.L., Liu Y.L., Lee H.L., Hsieh K.L., Huang W.C., Sung S.Y., Chang C.C., Changou C.A., Liang K.H., Hsieh T.H., Liu Y.R., Chao M.E., Chen W., Chu S.S., Cho E.C., Wong T.T. Molecular-clinical correlation in pediatric medulloblastoma: a cohort series study of 52 cases in Taiwan. Cancers 2020, 12: 653.
  6. Tran H.M., Wu K.S., Sung S.Y., Changou C.A., Hsieh T.H., Liu Y.R., Liu Y.L., Tsai M.L., Lee H.L., Hsieh K.L., Huang W.C., Liang M.L., Chen H.H., Lee Y.Y., Lin S.C., Ho D.M., Chang F.C., Chao M.E., Chen W., Chu S.S., Yu A.L., Yen Y., Chang C.C., Wong T.T. Upregulation of protein synthesis and proteasome degradation confers sensitivity to proteasome inhibitor bortezomib in Myc-atypical teratoid/rhabdoid tumors. Cancers 2020, 12:752.
  7. Huang C.S., Yu A.L., Tseng L.M., Chow L.W.C., Hou M.F., Hurvitz S.A., Schwab R.B., Murray J.L., Chang H.K., Chang H.T., Chen S.C., Kim S.B., Hung J.T., Ueng S.H., Lee S.H., Chen C.C., Rugo H.S. Globo H-KLH vaccine adagloxad simolenin (OBI-822)/OBI-821 in patients with metastatic breast cancer: phase II randomized, placebo-controlled study. Journal for ImmunoTherapy of Cancer 2020, 8: e000342.
  8. Midha M.K., Huang Y.F., Yang H.H., Fan T.C., Chang N.C., Chen T.H., Wang Y.T., Kuo W.H., Chang K.J., Shen C.Y., Yu A.L., Chiu K.P., Chen C.J. Comprehensive cohort analysis of mutational spectrum in early onset breast cancer patients. Cancers 2020, 12(8): 2089.
  9. Chang Y.H., Wu J.C., Yu H.M., Hsu H.T., Wu Y.T., Yu A.L., Yu C.T., Wong C.H. Design and synthesis of glycol-peptides as anti-cancer agents targeting thrombin-protease activated receptor-1 interaction. Chemical Communications 2020, 56: 5827-30.
  10. Diccianni M.B., Kempinska K., Gangoti J.A., Yu A.L., Sorkin L.S. Anti-GD2 induced allodynia in rats can be reduced by pretreatment with DFMO. Plos One 2020, 15(7):e0236115.
  11. Mody R., Yu A.L., Naranjo A., Zhang F.F., London W.B., Shulkin B.L., Parisi M.T., Servaes S., Diccianni M.B., Hank J.A., Felder M., Birstler J., Sondel P.M., Asgharzadeh S., Glade-Bender J., Katzenstein H., Maris J.M., Park J.R., Bagatell R. Irinotecan, Temozolomide, and Dinutuximab with GM-CSF in children with refractory or relapsed neuroblastoma: a report from the Children’s Oncology Group. Journal of Clinical Oncology 2020, 38:2160-9.
  12. Kuo M.W., Tsai H.H., Wang S.H., Chen Y.Y., Yu A.L., Yu J.* Yulink, predicted from evolutionary analysis, is involved in cardiac function. J. Biomed. Sci. 2021, 28: 7.
  13. Tseng Y.H., Chen Y.C., Yu A.L., Yu J.* Benzo[α]pyrene induces fibrotic changes and impairs differentiation in lung stem cells. Ecotoxicology Environmental Safety 2021, 210: 111892.
  14. Lin W.D., Fan T.C., Hung J.T., Yeo H.L., Wang S.H., Kuo C.W., Khoo K.H., Pai L.M., Yu J., Yu A.L.* Sialylation of CD55 by ST3GAL1 facilitates immune evasion in cancer. Cancer Immunol Res 2021, 9: 113-22.