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To understanding the molecular cues of pancreas regeneration provides several beneficial impacts either in basic or clinical diabetes research. In one hand, the elucidation of detailed cellular and molecular mechanism underlying pancreatic regeneration process shed the light for discovering novel factors essential for pancreas development. In the other hand, from the clinical point of view, to understand which factors playing important role in generating new-forming pancreatic, especially insulin-producing, cells makes it possible for therapeutic purpose of cellular treatment for diabetes. My main research foucs in Dr. Bonner-Weir's lab in Joslin is on investigating the molecular details in one of the classic regeneration models, 90% partial pancreaectomy (Px) in adult rats both in short-term and long-term time period. For short-term study (within 1 week after performance of surgery), we have found that in response to Px stimulation, the contribution of the dedifferentiation or
regression of differentiated duct epithelial cells to less-differentiated
progenitors, which expand and then redifferentiate into
differentiated endocrine and exocrine cells following the embryonic
developmental program can be detected. This mechanism of regeneration does not
rely on self-duplication or on stem cells, but rather relies on the
plasticity of the differentiation of cells within an organ. For long-term investigation, the hypothesis of "glucotoxicity" is tested. The experiments were designed to uncover the genetic profile by the comparison between control and 4-week Px rats using high-through put gene chip analysis. I also participated the study to explore the direct targets of Neurogenin 3, an essential transcription factor specifying pancreatic endocrine progenitors during normal pancreas development. This work is the collaboration with Dr. Amedeo Vetere in Joslin.
Education:
- Postdoctoral fellow, Lund Stem Cell Institute, Lunds University, Sweden (2010-present)
- Postdoctoral fellow, Section of Islet Transplantation & Cell Biology, Joslin Diabetes Center, One Joslin Place, Boston USA (2006-2010)
- MPhil/PhD, Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of BATH, UK (2002-2006)
- MSc, School of Dentistry, Department of Oral Biology, National Yang-Ming University, Peitou, Taipei, Taiwan (2000-2002)
- B.Sc., School of Medical Technology, Chang Gung University, Tao-Yuan 333, Taiwan (1997-2000)
Peer-review Publications:
1.Li W-C, Horb ME, Tosh D, Slack JMW (2005) In vitro transdifferentiation of hepatoma cells into functional pancreatic cells. Mechanism of Development 122: 835-847.
2.Li W-C, Yu W-Y, Quinlan JM, Burke ZD, Tosh D, (2005) The molecular basis of transdifferentiation. Journal of Cellular & Molecular Medicine 9: 569-582. Review article
3.Lin S-C, Li W-C, Shih J-W, Pan Y-R, Hong K-F, Lin J-J, (2006) The tea polyphenols EGCG and EGC repress the promoter activity and mRNA expression of hTERT. Cancer Letters 236: 80-88.
4.Li W-C, Ralphs KL, Slack JMW, Tosh D, (2007) Keratinocyte serum-free medium maintains long term liver gene expression and function in cultured rat hepatocytes by preventing the loss of liver-enriched transcription factors. International Journal of Biochemistry & Cell Biology 39: 541-554.
5.Ralphs KL*, Li W-C*, Burke ZD, Thowfeequ S; Al-Adsani A, Tosh D, (2007) Sources of hepatocytes for transplantation in hepatic dysfunction. Journal of Organ Dysfunction 3: 150-163 (*: authors contributed equally). Review article
6.Bonner-Weir S, Inada A, Yatoh S, Li W-C, Aye T, Toschi E, Sharma A, (2008) Transdifferentiation of pancreatic ductal cells to endocrine beta-cells. Biochem Soc Trans. 36: 353-356.
7.Vetere A*, Li W-C*, Paroni F, Juhl K, Guo L, Nishimura W, Dai X, Bonner-Weir S and Sharma A, (2010) OVO homologue-like 1 (OVOL1) transcription factor: a novel target of neurogenin-3 in rodent pancreas. Diabetologia 53: 115-122. (*: authors contributed equally).
8.Li W-C, J Rukstalis M, Nishimura W, Tchipashvili V, Habener JF, Sharma A, Bonner-Weir S, (2010) Activation of duct-derived-progenitor cells during pancreas regeneration in adult rats. Journal of Cell Science 123: 2792-2802.
9.Bonner-Weir S, Li W-C, Ouziel-Yahalom L, Guo L, Weir GC, Sharma A, (2010) -cell growth and regeneration: replication is only part of the story. Diabetes Accepted for publication
Book chapters:
1. Thowfeequ S, Li W-C, Slack JMW, Tosh D, (2008) Chapter 25: Reprogramming of Liver to Pancreas in Stem Cells in Regenerative Medicine, ISBN: 978-1-58829-797-6, Humana Press Publisher.
2. Li W-C, (2009) In vitro transdifferentiation of human hepatoma cells into pancreatic-like cells in Type 2 Diabetes: Methods and Protocols. Methods in Molecular Biology 560: 99-110. PISBN: 978-1-934115-15-2. Humana Press Publisher.
3. Burke ZD, Li W-C, Slack JMW, Tosh D, (2010) Isolation and culture of embryonic pancreas and liver in Mouse Cell Culture: Methods and Protocols. Methods in Molecular Biology 633: 91-99. PISBN: 978-1-58829-772-3. Humana Press Publisher.
4. Li W-C, Ralphs KL, Tosh D., (2010) Isolation and culture of adult mouse hepatocytes in Mouse Cell Culture: Methods and Protocols. Methods in Molecular Biology 633: 185-196. PISBN: 978-1-58829-772-3. Humana Press Publisher.
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