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沈家寧
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 沈家寧 (Chia-Ning Shen, Ph.D.)

  

Tel: 02-27899580 ext 301 (Office), 302 (Lab)

 Fax: 02-27899587

 Email: cnshen@gate.sinica.edu.tw

 

 

  Homepage

 

 

 

Education and Positions
  1. M.Sc., Institute of Biotechnology in Medicine, National Yang-Ming University , 1997
  2. Ph.D., Developmental Biology Program, University of Bath, , 2002
  3. Postdoctoral Fellow, Centre For Regenerative Medicine, University of Bath, United Kingdom, 2002–2004
  4. Assistant Research Fellow, Stem Cell Program, Genomics Research Center , Academia Sinica, 2004-present
  5. Adjunct Assistant Professor, Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, 2005-present
  6. Adjunct Assistant Professor, Graduate Institue of Clinical Medicine, Taipei Medical University, 2009-present

 

Research Interests

Plasticity means the ability of somatic cells to convert or to adapt to the new phenotype, which has been demonstrated in all examples of cell reprogramming including transdifferentiation, nuclear transplantation, cell fusion, neoplatic transformation and interconversions between somatic stem cells. To investigate the molecular basis of somatic cell conversion is clinically significant for two reasons: (1) Somatic cell conversion (transdifferentiation) predisposes to certain forms of neoplasia and cancer. (2) Somatic cell conversion is clinically important to the newly emerging science of regenerative medicine. To solve the shortage for organ transplantation, an alternative strategy is to produce isogenic cells to replace sick or damaged tissue from reprogrammed somatic cells. Currently, our group is focusing on development of diabetic therapies in combination with stem cells and somatic cell reprogramming. For example, we found insulin-producing cells can either be generated either from acinar transdifferentiation, dermal fibroblast derived “induced pulripotent stem cells” or liver stem/progenitor cells which can possibly be used for transplation therapies for diabetes. Furthermore, our group also aims to determine the possible mechanism regulating plastic transformation which may lead to development of neoplasia and cancer in pancreas.

 

 

  糖尿病是全球性流行之慢性疾病,根據國際衛生組織的資料顯示目前全世界有超過一億五千萬的糖尿病病患,預估二十年後會超過三億五千萬,其中將近五分之一是第一型糖尿或是缺乏胰島素分泌貝它細胞的病患,然因胰島來源缺乏導致無法大量用胰島移植以治療糖尿病患。本實驗室的研究主題之一在探討體細胞可塑性的調節機制,以及是否可將其運用在糖尿病的治療方面,特別是著眼於將病人的體細胞轉變為胰島素分泌貝它細胞,以為糖尿病提供一個可進行自體移植治療方法。例如誘導式多潛能幹細胞可以利用病人的體細胞製造出來,所以也可以避免或降低移植所造成的排斥問題,但是如何使這些”誘導式多潛能幹細胞(induced pluripotent stem cells)”再分化為具有特定功能的細胞,並且是否可以進一步地應用於疾病的移植治療來源,尚未有確切的答案。所以本實驗的目前研究重點是找尋可以使誘導式多潛能幹細胞分化為胰島素分泌貝它細胞的方法,進一步再將這些胰島素分泌貝它細胞糖尿病小鼠的模式,觀察其糖尿病症狀是否減輕,除預期可作為糖尿病細胞療法的先導研究外,並可對誘導式多潛能幹細胞的分化機轉作更深入的探討。

  此外在胰臟癌化的過程中,發現有胰腺細胞轉分化為胰管細胞甚至產生類肝細胞的現象,本實驗室發現經控制微環境的方式或致癌基因的表達,都可以改變胰腺細胞的可塑性,這結果提供了新的方向來進行胰臟癌化的機制研究,我們e更進一步建立誘導式Cre/loxP 特定點重組追蹤系統的基因轉殖小鼠來進行研究,以找尋這些造成胰臟早期癌化的前驅細胞源頭及轉化機制。

 

Selected publications
  1. Shen, C.N., J.M.W. Slack, and D. Tosh. 2000. Molecular basis of transdifferentiation of pancreas to liver. Nature Cell Biol. 2: 879-887.
  2. Tosh, D., C.N. Shen, and J.M.W Slack 2002. Differentiated properties of hepatocyte-like cells induced from the pancreatic cell. Hepatology 36:534-543.
  3. Shen C.N., M.E.Horb, J.M.W. Slack and D. Tosh 2003. Transdifferentiation of pancreas to liver. Mech. Dev. 120: 107-116.
  4. Horb, M.E., C.N. Shen, D. Tosh, and J.M.W. Slack 2003 Experimental conversion of liver to pancreas. Curr. Biol. 13(2): 105-115.
  5. Shen, C. N., J.R. Seckl, J.M.W. Slack, and D. Tosh. 2003. Glucocorticoid suppresses beta cell development and induces hepatic metaplasia in embryonic pancreas. Biochem. J. 375(1): 41-50.
  6. Kurash, J.K1., Shen C.N1., and D. Tosh 2004. Induction and expression of acute phase proteins in transdifferentiated hepatocyte. Exp. Cell Res. 292(2): 342-358. (1Authors contribute equally, Front cover)
  7. Shen, C.N., Z.D. Burke, and D. Tosh. 2004. Transdifferentiation, metaplasia and tissue regeneration. Organogenesis 1(2): 36-44.
  8. Wang, R.Y.L., C.N. Shen, M.H. Lin, D. Tosh and C.H. Shih. 2005. Hepatocyte-like cells transdifferentiated from pancreatic origin can support hepatitis B virus. J. Virol. 79: 13116-13128.
  9. Burke, Z.D., C.N. Shen, K.L. Ralphs, and D. Tosh. 2006. Characterization of liver function in TD hepatocytes. J. Cell. Physiol. 206:147-159.
  10. Tosh. D., C.N. Shen, M.R. Alison, C.E. Sarraf, and J.M.W. Slack 2007. Copper deprivation in rats induces islet hyperplasia and hepatic metaplasia in the pancreas. Biol. Cell. 99: 37-44.
  11. Shen, C.N., A. Petiot, C.Y. Chien, C. Dickson, J. M.W. Slack, and D. Tosh. 2007. All-trans Retinoic Acid suppresses exocrine differentiation and branching morphogenesis in the embryonic pancreas. Differentiation 75: 62-74.
  12. Susanto, J., Y.H. Lin, Y.N. Chen, C.R.Shen, Y.T.Yan, S.T. Tsai, C.H Chen, and C.N. Shen*. 2008. Porphyrin homeostasis maintained by ABCG2 regulates self-renewal of embryonic stem cells. PLoS ONE 3(12): e4023. (*corresponding author)
  13. Huang Y.H ., C. C. Chin, H.N. Ho, C.K. Chou, C.N. Shen, H.C. Kuo, T.J Wu, Y.C. Wu, Y.C. Hung, C.C. Chang,, T.Y Ling. 2009. Pluripotency of Mouse Spermatogonial Stem Cells Requires IGF-1. FASEB J. 23(7): 2076-87.
  14. C.N. Shen* and D. Tosh and 2010 Chapter 14: Transdifferentiation of pancreatic cells to hepatocytes. Hepatocyte: Methods and Protocols. Humana Press (Edited by Patrick Maurel. also in Methods in Molecular Biology 640: 273-280). ( *corresponding author)
  15. Wu, S.Y., C.C. Hsieh, R.R. Wu, J. Susanto, T.T. Liu, C.R. Shen,Y. Chen, I.F. Cheng, C.C. Su, F.P. Chang, H.M. Chang, D. Tosh, and C.N. Shen* 2010. Differentiation of pancreatic acinar cells to hepatocytes requires an intermediate cell type. Gastroenterology 138:2519-2530. (*corresponding author).
  16. Tsai H.A., R.R.Wu, I.C. Lee, H.Y.Chang, C.N. Shen* and Y.C.Chang*. 2010. Selection, enrichment and maintenance of Self-Renewal Liver Stem/Progenitor Cells utilizing Polypeptide Polyelectrolyte Multilayer Films. Biomacromolecules 11:994-1001 (*corresponding author).
  17. Al-Adsani A., Z.D. Burke, D. Eberhard, K. L. Lawrence, C.N. Shen, A K. Rustgi, H. Sakaue, J. M. Farrant and D Tosh. 2010. Dexamethasone treatment induces the reprogramming of pancreatic acinar cells to hepatocytes and ductal cells. PLoS One 5(10): e13650.
Popular science articles
  1. 沈家寧2007. 人造幹細胞 科學發展 414: 34-39.
  2. 沈家寧、謝綺哲、廖紋瑩 2009. 腫瘤幹細胞與癌症治療 科學月刊 40(7): 535-539.
  3. 沈家寧、陳志龍 2010. 體細胞重新編程技術與應用前景 中榮醫訊 142: 9-11