Shen, Chia-Ning 沈家寧

ShenCN 6x7副研究員

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Telephone: 02-27899580 ext.301 / 02-2787-1220(副主任辦公室)
[ CV ]




  • Ph.D., Developmental Biology Program, University of Bath, 2002
  • Postdoctoral Fellow, Centre For Regenerative Medicine, University of Bath, 2002-2004
  • Assistant Research Fellow, Genomics Research Center, Academia Sinica, 2004-2012
  • Associate Research Fellow, Genomics Research Center, Academia Sinica, 2012-present
  • Deputy Director and Associate Research Fellow, Genomics Research Center, Academia Sinica, 2013-present
  • Acting Division Director of Biotechnology Incubation Center, Genomics Research Center, Academia Sinica, 2018-present


  • ORS Award, Committee of Vice-chancellors and Principals of Universities of United Kingdom, 1999-2002
  • Conference Scholarship of International Federation of Cell Biology, 2000
  • Entrant of Santa Cruz Investigator Award, 2001
  • Conference Scholarship of British Society of Developmental Biology, 2000, 2001
  • Conference Scholarship of International Society of Differentiation, 2002
  • Travel award of Japan Society for the promotion of science for attending NPG Nature Asia-Pacific network meeting, 2007
  • Academia Sinica Significant Research Achievements, 2010
  • Travel award of International Society of Stem Cell Research, 2012
  • Rotary International Presidential Charity Award 2014-2015


The explosion of interest in somatic cell reprogramming has been fueled by their potential as a limitless source of cells to repair damaged tissues. However, whether naturally occurring cell reprogramming such as transdifferentiation (metaplasia) has a role in disease progression will also be needed to address. "Transdifferentiation" is the name used to describe the conversion of one differentiated cell type to another [Shen et al., Organogenesis 2004]. It belongs to a wider class of naturally occurring cell-type conversions known as "metaplasias" which include switches of cell fate between stem cells.  To investigate cell fate switches is important for three reasons. Firstly, identification of the switches involved may provide information on the molecular basis of normal developmental mechanisms. Secondly, understanding the rules for transdifferentiation between cell types will improve our ability to reprogram somatic cells for the purposes of therapeutic transplantation. Thirdly, transdifferentiation (metaplasias) predispose to neoplasia and so their prevention has a direct health benefit.

Currently, we have three research directions: (1) Islet transplantation has been recognized as an efficient therapeutic approach for treating type I diabetes, however, “shortage of donor supply” limited the usage. Whether stem cells exist in adult pancreatic tissues remains unclear, we have been trying to covert (transdifferentiate) cells of alternative resources to beta-cells. (2) Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of pancreatic cancer as the overall five years survival rate was 6%. It has been shown that the exocrine pancreas undergoes acinar-to-ductal transdifferentiation (metaplasias) in both chronic pancreatitis and pancreatic cancer suggesting a key role of acinar cell metaplasias in pancreatic carcinogenesis. We have been trying to identify the key factor that modulating acinar cell reprogramming in pancreatitis which would contribute to development of cancer in pancreas. (3) Existences of cancer stem/initiating cells in Pancreatic ductal adenocarcinoma (PDAC) and other forms of solid tumors may be the causes of chemo-resistance and cancer metastasis in patients. We are working on defining whether cancer stemness is derived from reprogramming and developing strategies for targeting cancer stem/initiating cells.

pluripotent stem cells

體細胞重新編程的研究,可以提供線索幫助我們鑑定細胞分化的關鍵機制,明瞭在促成組織修復及再生的機轉及搜尋癌症轉化的早期起始基因。我們主要有三個研究方向: (1)由於糖尿病的高盛行率及胰島移植的來源絕對缺乏,我們利用重新編程將組織細胞轉變功能胰島細胞及糖尿病小鼠模式,以驗證及開發進行糖尿病自體移植治療方法。(2)在胰臟癌化的過程中發現有胰腺細胞重新編程(轉分化)產生肝細胞或胰管細胞的現象,本實驗室結合細胞重新編程或建構胰腺專一表達突變基因的標定鼠及原位胰臟癌小鼠的方式,進行胰臟癌化的機制研究。(3)由於胰臟腫瘤幹細胞是造成胰腺癌高轉移性及抗藥性的重要原因,我們嘗試探討胰臟腫瘤幹細胞的特性是否來自癌化過程的特定細胞的重新編程,並以此為標的開發新的治療策略。


1. 沈家寧等著 2013 您不可不知道的幹細胞科技 五南圖書公司

2. 吳瑞仁、沈家寧 2012 體細胞重新編程技術開發與應用 中央研究院週報(知識天地) 1390: 8-10.

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

4. 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.

5. 沈家寧 2007. 人造幹細胞 科學發展 414: 34-39.


  • C.H. Peng. K. C. Huang, H.E. Lu, S.H. Syu, A.A. Yarmishyn, J.F. Lu, W. Buddhakosai, T.C. Lin, C.C. Hsu., D.K. Hwang, (C.N. Shen), S.J. Chen, S.H. Chiou, 2018, “Generation of induced pluripotent stem cells from a patient with X-linked juvenile retinoschisis.”, Stem Cell Research, 29, 152-126. (SCI)
  • Chuang, T.J., Chen, Y.J., Chen, C.Y., Mai, T.L., Wang, Y.D., Yeh, C.S., Yang, M.Y., Hsiao, Y.T., Chang, T.H., Kuo, H.C., Cho, H.H., (Shen, C.N.,) Kuo, H.C., Lu, M.Y., Chen, Y.H., Hsieh, S.C, Chiang, T.W.,, 2018, “Integrative transcriptome sequencing reveals extensive alternative trans-splicing and cis-backsplicing in human cells”, NUCLEIC ACIDS RESEARCH, 46(7), 3671-3691. (SCI)
  • T.L. Chen, Y.W. Lin, Y.B. Chen, J.J. Lin, T.L. Su, (C.N. Shen*), T.C. Lee*, 2018, “A low-toxicity DNA-alkylating N-mustard-quinoline conjugate with preferential sequence specificity exerts potent antitumor activity against colorectal cancer”, Neoplasia, 20(2), 119-130. (SCI)
  • Wu YR, Wang AG, Chen YT, Yarmishyn AA, Buddhakosai W, Yang TC, Hwang DK, Yang YP, (Shen CN), Lee HC, Chiou SH, Peng CH, Chen SJ, 2018, “Bioactivity and Gene Expression Profiles of hiPSC-generated Retinal Ganglion Cells in MT-ND4 Mutated Leber's Hereditary Optic Neuropathy.”, Experimental cell research, 363, 299-309. (SCI)
  • S.C.Tang, L. Baeyens, (C.N. Shen), S.J. Peng, H.J. Chien, D.W. Scheel, C.E. Chamberlain, M.S.German., 2018, “Human pancreatic neuro-insular network in health and fatty infiltration.”, Diabetologia, 61(1), 168-181. (SCI)
  • S.C.Tang, (C.N. Shen*), P.Y. Lin, S.J. Peng, H.J. Chien, Y.H. Chou, C.E. Chamberlain, P.J. Pasricha., 2018, “Pancreatic neuro-insular network in young mice revealed by 3D panoramic histology.”, Diabetologia, 61(10), 158-167. (SCI)
  • W.C. Yang, Y.S. Hwang, Y.Y. Chen, C.L. Liu, (C.N. Shen), W.H. Hong, S.M. Lo, C.R. Shen, 2017, “Interleukin-4 supports the suppressive immune responses elicited by regulatory T cells”, Frontiers in Immunology, 8, 1508. (SCI)
  • C.L. Hsieh, C.M. Liu, H.A. Chen, S.T. Yang, K. Shigemura, K. Kitagawa, F. Yamamichi, M. Fujisawa, Y.R. Liu, W.H. Lee, K.C. Chen, (C.N. Shen), C.C. Lin, L. Chung and S.Y. Sung., 2017, “Reactive oxygen species-mediated switching expression of MMP-3 in stromal fibroblasts and cancer cells during prostate cancer progression.”, Scientific reports, 7(1), 9065. (SCI)
  • Y.T. Lin, C.K. Wang, S.C. Yang, S.C. Hsu, H. Lin, F.P. Chang, T. C. Kuo, (C.N. Shen), M. Hsiao, P.M. Chiang, F. L. Lu, and J. Lu, 2017, “Elimination of undifferentiated human embryonic stem cells by cardiac glycosides”, Scientific Reports, 7(1), 5289. (SCI)
  • Hsieh, C.C., I.M. Shyu, W.Y. Liao, T.H. Chen, S.E. Wang, P.C. Lu, P.Y. Lin, Y.B. Chen, W.Y. Mao, H.Y. Han, M. Hsiao, W.B. Yang, W.S. Li, Y.P. Sher, (C.N. Shen*), 2017, “Elevation of beta-galactoside alpha 2,6-sialyltransferase 1 modulated in a fructose-responsive manner promotes pancreatic cancer metastasis”, Oncotarget, 8(5), 7691-7709. (SCI)
  • F.P. Chang, C.H. Cho, C.R. Shen, C.Y. Chien, L.W.Ting, H.S. Lee, (C.N. Shen*), 2016, “PDGF Facilitates Direct Lineage Reprogramming of Hepatocytes to Functional ß-Like Cells Induced by Pdx1 and Ngn3”, Cell transplantation, 25(10), 1893-1909. (SCI)
  • Chien, C.Y., T.A. Yuan, Candy.H.H. Cho, F.P. Chang, W.Y. Mao, R.R. Wu, H.S. Lee*, (C.N. Shen*), 2016, “All-trans retinoic acid ameliorates glycemic control in diabetic mice via modulating pancreatic islet production of vascular endothelial growth factor-A”, Biochemical and Biophysical Research Communications, 477(4), 874-880.. (SCI)
  • Liu CM, Hsieh CL, (Shen CN), Lin CC, Shigemura K, Sung SY, 2016, “Exosomes from the tumor microenvironment as reciprocal regulators that enhance prostate cancer progression.”, International journal of urology, 23(9), 734-744. (SCI)
  • Lin PY, Peng SJ, (Shen CN*), Pasricha PJ, Tang SC, 2016, “PanIN-associated pericyte, glial, and islet remodeling in mice revealed by 3-D pancreatic duct lesion histology.”, American Journal of Physiology-Gastrointestinal and Liver Physiology, 311(3), G412-G422. (SCI)
  • Chien, C.Y., H.S. Lee*, Candy.H.H. Cho, K.I. Lin, D. Tosh, R.R. Wu, W.Y. Mao, (C.N. Shen*), 2016, “Maternal Vitamin A deficiency during pregnancy affects vascularized islet development”, Journal of Nutritional Biochemistry, 36, 51-59. (SCI)
  • Lien HW, Yuan RY, Chou CM, Chen YC, Hung CC, Hu CH, Hwang SP, Hwang PP, (Shen CN), Chen CL, Cheng CH, Huang CJ, 2016, “Zebrafish cyclin Dx is required for development of motor neuron progenitors, and its expression is regulated by hypoxia-inducible factor 2alpha.”, Scientific reports, 6, 28297. (SCI)
  • Chang HM, Huang WY, Lin SJ, Huang WC, Shen CR, Mao WY, (Shen CN*), 2016, “ABCG2 deficiency in skin impairs re-epithelialization in cutaneous wound healing.”, Experimental dermatology, 25(5), 355-361. (SCI)
  • Cheung SK, Chuang PK, Huang HW, Hwang-Verslues WW, Cho CH, Yang WB, (Shen CN), Hsiao M, Hsu TL, Chang CF, Wong CH, 2016, “Stage-specific embryonic antigen-3 (SSEA-3) and beta3GalT5 are cancer specific and significant markers for breast cancer stem cells.”, Proceedings of the National Academy of Sciences of the United States of America, 113(4), 960-965. (SCI)
  • Chen CY, Lee DS, Yan YT, (Shen CN), Hwang SM, Tone Lee S, Hsieh PC, 2015, “Bcl3 Bridges LIF-STAT3 to Oct4 Signaling in the Maintenance of Naive Pluripotency.”, Stem cells, 33(12), 3468-3480. (SCI)
  • Chang JS, Su CY, Yu WH, Lee WJ, Liu YP, Lai TC, Jan YH, Yang YF, (Shen CN), Shew JY, Lu J, Yang CJ, Huang MS, Lu PJ, Lin YF, Kuo ML, Hua KT, Hsiao M, 2015, “GIT1 promotes lung cancer cell metastasis through modulating Rac1/Cdc42 activity and is associated with poor prognosis.”, Oncotarget, 6(34), 36278-36291. (SCI)
  • Liaw CC, Yang YL, Lin CK, Lee JC, Liao WY, (Shen CN), Sheu JH, Wu SH., 2015, “New Meroterpenoids from Aspergillus terreus with Inhibition of Cyclooxygenase-2 Expression”, Organic Letters, 17(10), 2330-2333. (SCI)
  • Lee IC, Liu YC, Tsai HA, (Shen CN), Chang YC, 2014, “Promoting the selection and maintenance of fetal liver stem/ progenitor cell colonies by layer-by-layer polypeptide tethered supported lipid bilayer.”, ACS applied materials & interfaces, 6(23), 20654-20663. (SCI)
  • CL Chen, LJ Wang, YT Yan, HW Hsu, HL Su, FP Chang, PCH Hsieh, SM Hwang, (CN Shen*), 2014, “Cyclin D1 Acts as a Barrier to Pluripotent Reprogramming by Promoting Neural Progenitor Fate Commitment”, FEBS Letters, 588(21), 4008-4017. (SCI)
  • Yang YF, Jan YH, Liu YP, Yang CJ, Su CY, Chang YC, Lai TC, Chiou J, Tsai HY, Lu J, (Shen CN), Shew JY, Lu PJ, Lin YF, Huang MS, Hsiao M, 2014, “Squalene synthase induces tumor necrosis factor receptor 1 enrichment in lipid rafts to promote lung cancer metastasis.”, American journal of respiratory and critical care medicine, 190(6), 675-687. (SCI)
  • Tsai HY, Yang YF, Wu AT, Yang CJ, Liu YP, Jan YH, Lee CH, Hsiao YW, Yeh CT, (Shen CN), Lu PJ, Huang MS, Hsiao M, 2013, “Endoplasmic reticulum ribosome-binding protein 1 (RRBP1) overexpression is frequently found in lung cancer patients and alleviates intracellular stress-induced apoptosis through the enhancement of GRP78.”, Oncogene, 32(41), 4921-4931. (SCI)
  • Lin YH, Chang HM, Chang FP, Shen CR, Liu CL, Mao WY, Lin CC, Lee HS, (Shen CN*), 2013, “Protoporphyrin IX accumulation disrupts mitochondrial dynamics and function in ABCG2-deficient hepatocytes.”, FEBS letters, 587(19), 3202-3209. (SCI)
  • WY Liao, CC Liaw, YC Huang, HY Han, HW Hsu, SM Hwang, SC Kuo and (CN Shen*), 2013, “Cyclohexylmethyl flavonoids suppress propagation of breast cancer stem cells via downregulation of NANOG”, Evidence-based Complementary and Alternative Medicine, 2013, 170261. (SCI)
  • Liu YP, Yang CJ, Huang MS, Yeh CT, Wu AT, Lee YC, Lai TC, Lee CH, Hsiao YW, Lu J, (Shen CN), Lu PJ, Hsiao M, 2013, “Cisplatin selects for multidrug-resistant CD133+ cells in lung adenocarcinoma by activating Notch signaling.”, Cancer Research, 73(1), 406-416. (SCI)
  • Tsai ST, Tsou CC, Mao WY, Chang WC, Han HY, Hsu WL, Li CL, (Shen CN*), Chen CH*, 2012, “Label-free quantitative proteomics of CD133-positive liver cancer stem cells.”, Proteome science, 10(1), 69. (SCI)
  • Tsai HA, (Shen CN), Chang YC, 2012, “The Use of Surface Properties to Control the Growth and Differentiation of Mouse Fetal Liver Stem/Progenitor Cell Colonies.”, Biomacromolecules, 13(11), 3483-3493. (SCI)
  • Wu YC, Ling TY, Lu SH, Kuo HC, Ho HN, Yeh SD, (Shen CN*), Huang YH*, 2012, “Chemotherapeutic Sensitivity of Testicular Germ Cell Tumors Under Hypoxic Conditions Is Negatively Regulated by SENP1-Controlled Sumoylation of OCT4.”, Cancer Research, 72(19), 4963-4973. (SCI)
  • Chu CY, Chen CF, Rajendran RS, (Shen CN), Chen TH, Yen CC, Chuang CK, Lin DS, Hsiao CD, 2012, “Overexpression of Akt1 enhances adipogenesis and leads to lipoma formation in zebrafish.”, PloS One, 7(5), e36474. (SCI)
  • Liao WY, (Shen CN), Lin LH, Yang YL, Han HY, Chen JW, Kuo SC, Wu SH, Liaw CC, 2012, “Asperjinone, a Nor-Neolignan, and Terrein, a Suppressor of ABCG2-Expressing Breast Cancer Cells, from Thermophilic Aspergillus terreus.”, Journal of Natural Products, 75(4), 630-635. (SCI)
  • Liang YJ, Yang BC, Chen JM, Lin YH, Huang CL, Cheng YY, Hsu CY, Khoo KH, (Shen CN), Yu J, 2011, “Changes in Glycosphingolipid Composition During Differentiation of Human Embryonic Stem Cells to Ectodermal or Endodermal Lineages.”, Stem Cells, 29(12), 1995-2004. (SCI)
  • Liaw CC, Liao WY, Chen CS, Jao SC, Wu YC, (Shen CN*), Wu SH*, 2011, “The calcium-chelating capability of tetrahydrofuranic moieties modulates the cytotoxicity of annonaceous acetogenins.”, Angewandte Chemie-International Edition, 50(34), 7885-7891. (SCI)
  • C.F.Chen, C.Y. Chu, T.H. Chen, S.J. Lee, (C.N. Shen*), and C.D. Hsiao*, 2011, “Establishment of a Transgenic Zebrafish Line for Superficial Skin Ablation and for Functionally Validation of Anti-Apoptotic Pathways in vivo”, PLoS One, 6(5), e20654. (SCI)
  • Al-Adsani A, Burke ZD, Eberhard D, Lawrence KL, (Shen CN), Rustgi AK, Sakaue H, Farrant JM, Tosh D, 2010, “Dexamethasone Treatment Induces the Reprogramming of Pancreatic Acinar Cells to Hepatocytes and Ductal Cells.”, PLoS ONE, 5(10), e13650. (SCI)
  • Wu SY, Hsieh CC, Wu RR, Susanto J, Liu TT, Shen CR, Chen Y, Su CC, Chang FP, Chang HM, Tosh D, (Shen CN*), 2010, “Differentiation of pancreatic acinar cells to hepatocytes requires an intermediate cell type.”, Gastroenterology, 138, 2519-2530. (SCI)
  • Tsai HA, Wu RR, Lee IC, Chang HY, (Shen CN*), Chang YC*, 2010, “Selection, Enrichment, and Maintenance of Self-Renewal Liver Stem/Progenitor Cells Utilizing Polypeptide Polyelectrolyte Multilayer Films.”, Biomacromolecules, 11, 994-1001. (SCI)
  • (Shen CN*), Tosh D, 2010, “Transdifferentiation of pancreatic cells to hepatocytes”, Methods in molecular biology, 640, 273-280.
  • Yang CJ, Liu YK, Liu CL, (Shen CN), Kuo ML, Su CC, Tseng CP, Yen TC, Shen CR, 2009, “Inhibition of Acidic Mammalian Chitinase by RNA Interference Suppresses OVA-sensitized Allergic Asthma.”, Human gene therapy, 20(12),1597–1606. (SCI)
  • Yang YL, Liao WY, Liu WY, Liaw CC, (Shen CN), Huang ZY, Wu SH, 2009, “Discovery of New Natural Products by Intact-Cell Mass Spectrometry and LC-SPE-NMR: Malbranpyrroles, Novel Polyketides from Thermophilic Fungus Malbranchea sulfurea.”, Chemistry-A European Journal, 15(43), 11573-11580. (SCI)
  • Huang YC, Hwang TL, Chang CS, Yang YL, (Shen CN), Liao WY, Chen SC, Liaw CC, 2009, “Anti-inflammatory flavonoids from the rhizomes of Helminthostachys zeylanica.”, Journal of natural products, 72(7), 1273-1278. (SCI)
  • Huang YH, Chin CC, Ho HN, Chou CK, (Shen CN), Kuo HC, Wu TJ, Wu YC, Hung YC, Chang CC, Ling TY, 2009, “Pluripotency of mouse spermatogonial stem cells maintained by IGF-1- dependent pathway.”, FASEB Journal, 23(7), 2076-2087. (SCI)
  • J. Susanto, 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. (SCI)
  • (C.N. Shen), 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. (SCI)
  • D. Tosh, (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”, Biology of the cell, 99, 37-44. (SCI)
  • Z. D. Burke, (C. N. Shen), K. L. Ralphs and D. Tosh, 2006, “Characterization of liver function in transdifferentiated hepatocytes”, Journal of cellular physiology, 206(1), 147-159. (SCI)
  • R.Y.L. Wang, (C. N. Shen), M. H. Lin, D. Tosh and C. H. Shih, 2005, “Hepatocyte-like cells transdifferentiated from a pancreatic origin can support replication of hepatitis B virus”, Journal of virology, 79, 13116-13128. (SCI)
  • (C. N. Shen), Z. D. Burke and D. Tosh, 2004, “Transdifferentiation, metaplasia, and tissue regeneration”, Organogenesis, 1(2), 36-44. (SCI)
  • (C. N. Shen), J. K. Kurash and D. Tosh, 2004, “Induction and regulation of acute phase proteins in transdifferentiated hepatocytes”, Experimental cell research, 292, 342-358. (SCI)
  • M. E. Horb, (C. N. Shen), D. Tosh and J. M. Slack, 2003, “Experimental conversion of liver to pancreas”, Current biology, 13, 105-115. (SCI)
  • (C. N. Shen), J. R. Seckl, J. M. Slack and D. Tosh, 2003, “Glucocorticoids suppress beta-cell development and induce hepatic metaplasia in embryonic pancreas”, Biochemical journal, 375, 41-50. (SCI)
  • (Shen CN), Horb ME, Slack JM, Tosh D, 2003, “Transdifferentiation of pancreas to liver.”, Mechanisms of development, 120(1), 107-16. (SCI)
  • D. Tosh, (C. N. Shen) and J. M. Slack, 2002, “Differentiated properties of hepatocytes induced from pancreatic cells”, Hepatology, 36, 534-543. (SCI)
  • (C. N. Shen), J. M. Slack and D. Tosh, 2000, “Molecular basis of transdifferentiation of pancreas to liver”, Nature Cell Biology, 2, 879-887. (SCI)