黎萬君 教授 (LI, WAN-CHUN)

經歷：

經歷：

現職：

國立陽明交通大學牙醫學院 口腔生物研究所 所長

台灣幹細胞學會 秘書長

專長：(癌)細胞分子生物學、內分泌學(糖尿病學)、幹細胞生物學

聯絡電話：(02) 2826-7255

傳真電話：(02) 2826-4053

電子郵件：wcli@nycu.edu.tw

研究方向

代謝平衡是個體維持生命之必需。生物體能將由環境中攝取之醣類、蛋白質和脂質轉換成有利於細胞吸收的小分子進而產生細胞所需的能量及生物質量。近年研究顯示，若外在或內在參與細胞代謝之分子、中間產物或離子數量/活性失衡，會促使正常細胞轉性，進而生成癌症。然而，腫瘤生成過程為何需要代謝轉換？代謝轉換是否為致癌的主要因子則還未明瞭。以此為基礎，本實驗室的研究方向欲探討：依據組織學型態、腫瘤生長移動狀態及對於藥物的感受性等特性所區分各階段癌細胞中不同代謝路徑活性；並瞭解腫瘤細胞在惡化的過程中，如何進行動態的代謝相關途徑重組。另一方面，癌細胞如何因應微環境代謝失衡所引發之生理失衡，調整自體相關代謝路徑活性，讓自己存活也是研究的一大重點。我們預期，若能找出主要決定癌代謝特性的分子，將可利用改變癌細胞特定代謝途徑反轉癌細胞的惡性程度；亦可以此為基礎，篩選以細胞代謝為基礎的有效標靶治療方式，開發出新穎抗癌藥物。

綜合以上研究方向，目前實驗室主要研究目的為:

1. 探討頭頸癌細胞中，糖解作用(Glycolysis pathway)、脂質新生(Lipogenesis)、氧化磷酸化(Oxidative Phosphorylation)及胺基酸等代謝途徑調控頭頸癌細胞癌化特性的細胞及分子機制。以多方面的代謝分析，釐清不同代謝路徑及代謝可塑性(Metabolic plasticity)在癌化過程所扮演的腳色。
2. 瞭解頭頸癌細胞中，內生性及外在代謝途徑調控癌幹細胞(CICs/CSCs)的細胞分子機制。以不同的代謝分析，釐清癌幹胞特有代謝印記，以期能更特定利用細胞代謝調控消滅幹性高的頭頸癌細胞。
3. 建立對於化療藥物(Chemotherapy)、放療(Radiation therapy)及光動力治療(Photodynamic therapy)具有不同抗性的頭頸癌細胞，探究在感受性不同的細胞之間，其代謝途徑相關基因及代謝體的差異。藉此以代謝為出發點，找尋癌症難以根治的癥結點。
4. 建立攜有不同代謝分子控制報導基因之頭頸癌細胞，利用含有天然藥物的化學藥庫，篩選以細胞代謝為基礎之分子抗癌標靶，並利用篩選出的藥物透過細胞及活體實驗進一步觀察其抑癌相關分子機制。

研究計畫（5年內）

發表著作(*:通訊作者)

期刊論文:

1. Hsieh Y-T, Tu H-F, Yang M-H, Chen Y-F, Lan X-Y, Huang C-L, Chen H-M, Li W-C* (2021). Mitochondrial genome and its regulator TFAM modulates head and neck tumourigenesis through intracellular metabolic reprogramming and activation of oncogenic effectors. Cell Death Dis. 12: 961. (SCI)
2. Wong NK, Luo S, Chow EYD, Meng F, Adesanya A, Sun J, Ma HMH, Jin W, Li W–C, Yip SP, Huang C-L* (2021). The Tyrosine Kinase-Driven Networks of Novel Long Non-coding RNAs and Their Molecular Targets in Myeloproliferative Neoplasms. Front Cell Dev Biol. 9: 643043. (SCI)
3. Su Y-F, Chen Y-J, Tsai F-T, Li W–C, Hsu M-L, Wang D-H, Yang C-C* (2021). Current Insights into Oral Cancer Diagnostics. Diagnostics (Basel) 11:1287. (SCI)
4. Juang J-H*, Wang J-J, Shen C-R, Chen C-Y, Kao C-W, Chen C-L, Lin S-H, Wu S-T, Li W–C, Tsai Z-T (2021). Magnetic Resonance Imaging of Transplanted Porcine Neonatal Pancreatic Cell Clusters Labeled with Chitosan-Coated Superparamagnetic Iron Oxide Nanoparticles in Mice. Polymers (Basal) 13: 1238. (SCI)
5. Chen S-G, Ugwu F, Li W-C, Caplice NM, Petcu EB, Yip SP, Huang C-L* (2021). Vascular Tissue Engineering: Advanced Techniques and Gene Editing in Stem Cells for Graft Generation. Tissue Eng Part B Rev. 27:14-28. (SCI)
6. Chiu C-H, Leu J-D, Lin T-T, Su P-H, Li W-C, Lee Y-J*, Cheng D-C*(2020). Systematic Quantification of Cell Confluence in Human Normal Oral Fibroblasts. Applied Sciences 10:9146. (SCI)
7. Yang H#, Wei Y-C#, Li W-C#, Chen H-Y, Lin H-Y, Chiang C-P, Chen H-M* (2020). Natural Compounds Modulate Drug Transporter Mediated Oral Cancer Treatment. Biomolecules 10:1335 (#: authors contributed equally) (SCI)
8. Lan X-Y, Chung T-T, Huang C-L, Lee Y-J, Li W-C* (2020). Traditional Herbal Medicine Mediated Regulations during Head and Neck Carcinogenesis. Biomolecules 10:E1321. (SCI)
9. Li W-C*, Huang C-H, Hsieh Y-T, Chen T-Y, Cheng L-H, Chen C-Y, Liu C-J, Chen H-M, Huang C-L, Lo J-F, Chang K-W (2020). Regulatory Role of Hexokinase 2 in Modulating Head and Neck Tumorigenesis. Front Oncol. 10:176. (SCI)
10. Yang W-S, Lin T-Y, Chang L, Yeh W-W, Huang S-C, Chen T-Y, Hsieh Y-T, Chen S-T, Li W-C, Pan C-C, Campbell M, Yen C-H, Chen YA, Chang P-C*(2020). HIV-1 Tat Interacts with a Kaposi’s Sarcoma-Associated Herpesvirus Reactivation-Upregulated Antiangiogenic Long Noncoding RNA, LINC00313, and Antagonizes Its Function. J Virol. 94: pii: e01280-19.
11. Hsieh Y-T, Chen Y-F, Lin S-C, Chang K-W, Li W-C* (2019). Targeting Cellular Metabolism Modulates Head and Neck Oncogenesis. Int J Mol Sci. 20: pii: E3960.
12. Chen T-Y^#, Hsieh Y-T^#, Huang J-M^#, Liu C-J, Chuang L-T, Huang P-C, Kuo T-Y, Chia H-Y, Chou C-Y, Chang C-W, Chen Y-F, Chen H-M, Lo J-F, Li W-C* (2019). Determination of Pyruvate Metabolic Fates Modulates Head and Neck Tumourigenesis. Neoplasia 21:641-652 (#: authors contributed equally)
13. Yang M-C, Wang D-H, Wu H-T, Li W-C, Chang T-Y, Lo W-L*, Hsu M-L* (2019). Correlation of Magnetic Resonance Imaging Grades with Cytokine Levels of Synovial Fluid of Patients with Temporomandubular Joint Disorders: A Cross-sectional Study. Clinical Oral Investigations 23:3871-3878
14. Yang M-C, Wang D-H, Cherng J-H, Li W-C, Lin P-Y, Hsu W-E, Hsu M-L* (2019). Role of Link N in Modulating Inflammatory Conditions. Journal of Oral & Facial Pain and Headache, 33:114-122.
15. Li W-C, Chen C-Y, Kao C-W, Huang P-C, Hsieh Y-T, Kuo T-Y, Chen T-Y, Chia H-Y, Juang J-H* (2018). Porcine Neonatal Pancreatic Cell Clusters Maintain Their Multipotency in Culture and After Transplantation. Scientific Reports, 8:8212.
16. Rezanejad H, Ouziel-Yahalom L, Keyzer CA, Sullivan BA, Hollister-Lock J, Li W-C, Guo L, Deng S, Lei J, Markmann J, Bonner-Weir S* (2018). Heterogeneity of SOX9 and HNF1β in Pancreatic Ducts Is Dynamic. Stem Cell Reports, 10(3):725-738.
17. Wang M-C, Yeh L-Y, Shih W-Y, Li W-C, Chang K-W*, Lin S-C* (2017). Portland cement induces human periodontal ligament cells to differentiate by upregulating miR-146a. Journal of the Formosan Medical Association, 117(4):308-315.
18. Tsai W-L, Yeh P-H, Tsai C-Y, Ting C-T, Chiu Y-H, Tao M-H, Li W-C*, Hung S-C*(2017) Efficient Programming of Human Mesenchymal Stem Cell Derived Hepatocytes by Epigenetic Regulations. Journal of Gastroenterology and Hepatology. 32: p261-269.
19. Lee Y-L^#, Li W-C^#, Tsai T-H, Chiang H-Y, Ting C-T* (2016) Body mass index and cholesterol level predict surgical outcome in patients with hepatocellular carcinoma in taiwan – a cohort study. Oncotarget. 7: p22948-22959. (#: authors contributed equally).
20. Chien H-Y, Chen C-Y, Chiu Y-H, Lin Y-C, Li W-C* (2016). Differential microRNA Profiles Predict Diabetic Nephropathy Progression in Taiwan. International Journal of Medical Sciences. 13: p457-465
21. Liu C-J, Chang W-J, Chen C-Y, Sun F-J, Cheng H-W, Chen T-Y, Lin S-C, Li W-C* (2015). Dynamic Cellular and Molecular Modulations of Diabetes Mediated Head and Neck Carcinogenesis. Oncotarget. 6: p29268-29284.
22. Sun X, Sun Y, Li W-C, Chen C-Y, Chiu Y-H, Chien H-Y, Wang Y*. (2015). Association of Thyroid-stimulating Hormone and Cardiovascular Risk Factors. Internal Medicine, 54: p2537-2544.
23. Chien H-Y, Lee T-P, Chen C-Y, Chiu Y-H, Lin Y-C, Lee L-S, Li W-C* (2015). Circulating microRNA as a Diagnostic Marker in Populations with Type 2 Diabetes Mellitus and Diabetic Complications. Journal of the Chinese Medical Association. 78: p204-211.
24. Ting C-T, Li W-C, Chen C-Y, Tsai T-H* (2015). Preventive and therapeutic role of traditional Chinese herbal medicine in hepatocellular carcinoma. Journal of the Chinese Medical Association. 78: p139-144.
25. Li W-C; Lee P-L; Chou I-C; Chang W-J; Lin S-C; Chang K-W* (2015). Molecular and cellular cues of diet-associated oral carcinogenesis – with an emphasis on areca nut induced oral cancer development. Journal of Oral Pathology & Medicine. 44: p167-177.
26. Chang Y-C, Li W-C, Twu N-F, Li H-Y, Lo W-L, Chang Y-L, Lee Y-Y, Lin C-F, Shih Y-H, Chen M-T (2014). Induction of dental pulp-derived induced pluripotent stem cells in the absence of c-Myc for differentiation into neuron-like cells. Journal of the Chinese Medical Association. 77: p618-625.
27. O’Neill KE; Thowfeequ S; Li W-C; Eberhard D; Dutton JR; Tosh D; Slack JMW* (2014). Hepatocyte-ductal transdifferentiation is mediated by reciprocal repression of SOX9 and C/EBPalpha. Cellular Reprogramming. 16: p314-323.
28. Kesavan G; Lieven O; Mamidi A; LoÅNf-OÅNhlin Z; Johansson JK; Li W-C; Lomme S; Greiner TU; Semb H* (2014). Cdc42/N-WASP signaling links actin dynamics to pancreatic beta cell delamination and differentiation. Development. 141: p685-696.
29. Wu J Y-T; Li W-C; Chien W-Z; Lee Y-L* (2013). Combined Treatment Using Complete Dentures and Palatal Obturator for Cleft Palate: A Case Report. Taipei City Medical Journal, 10: p173-178.
30. Sun X, Gao L, Chien H-Y, Li W-C*, Zhao J* (2013). The Regulation and Function of the NUAK Family. Journal of Molecular Endocrinology, 51:R15-22.
31. Wu F, Guo L, Jakubowski A, Su L, Li W-C, Bonner-Weir S*, Burkly LC* (2013). TNF-like Weak Inducer of Apoptosis (TWEAK) Promotes Beta Cell Neogenesis from Pancreatic Ductal Epithelium in Adult Mice. PLOS ONE, 8:
32. Bonner-Weir S*, Guo L, Li W-C, Ouziel-Yahalom L, Lysy P, Weir GC, Sharma A (2013) Islet neogenesis: a possible pathway for β-cell replenishment. Rev Diabet Stud. 9: p407-16
33. Wang MC, Hung PS, Tu HF, Shih WY, Li W-C, Chang KW* (2012) Lipopolysaccharide induces the migration of human dental pulp cells by up-regulating miR-146a.J Endod.; 38: p1598-603.
34. Aguayo-Mazzucato C, Koh A, El Khattab I, Li W-C, Toschi E, Jermendy A, Juhl K, Mao K, Weir GC, Sharma A, Bonner-Weir S* (2011) MafA and Pdx1 contribute to acquisition of glucose-responsive insulin secretion in neonatal rat beta cells, Diabetologia 54: p583-593.
35. Bonner-Weir S*, Li W-C, Ouziel-Yahalom L, Guo L, Weir GC, Sharma A (2010) Beta cell growth and regeneration: replication is only part of the story. Diabetes 59: p2340-2348.
36. Li W-C, Rukstalis JM, 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: p2792-2802.
37. Vetere A#*, Li W-C#, Paroni F, Juhl K, Guo L, Nishimura W, Dai X, Bonner-Weir S, Sharma A (2010) OVO homologue-like 1 (OVOL1) transcription factor: a novel target of neurogenin-3 in rodent pancreas. Diabetologia 53: p115-122. (#: authors contributed equally).
38. 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: p353-356.
39. 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: p150-163 (#: authors contributed equally).
40. 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: p541-554.
41. 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: p80-88.
42. Li W-C, Yu W-Y, Quinlan JM, Burke ZD, Tosh D* (2005) The molecular basis of transdifferentiation. Journal of Cellular & Molecular Medicine 9: p569-582.
43. Li W-C, Horb ME, Tosh D, Slack JMW* (2005) In vitro transdifferentiation of hepatoma cells into functional pancreatic cells. Mechanism of Development 122: p835-847.

專書章節：

1. Li W-C, Chen C-Y, Chien H-Y, Bonner-Weir S*  (2016) “Pancreatic regeneration after partial pancreatectomy in rodents” in A.A.  

Hardikar (ed.), Pancreatic Islet Biology, Stem cell Biology and Regenerative Medicine p111-123. Springer International Publishing

2. 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: p185-196. PISBN: 978-1-58829-772-3. 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: p91-99. PISBN: 978-1-58829-772-3. Humana Press Publisher.
4. 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: p99-110. PISBN: 978-1-934115-15-2. Humana Press Publisher.
5. Thowfeequ S, Li W-C, Slack JMW, Tosh D* (2008) “Reprogramming of Liver to Pancreas” in Stem Cells in Regenerative Medicine; Methods in Molecular Biology 482: p407-418. ISBN: 978-1-58829-797-6, Humana Press Publisher.

專利

1. Li W-C, Tosh D, Slack JMW (2006) : Hepatocyte culture