LI Wan-Chun

Name 
LI Wan-Chun

Field of Specialty

Cell & Molecular Biology, Endocrinology (Diabetes), Stem Cell Biology, Oncology

Research Description

Metabolic balance is essential in regulating physiological homeostasis. Considering great energy and biomass demand for cell growth, cancer cells exhibited unique metabolic signature compared to normal cells. The reversal of the cancerous metabolic cues had therefore been regarded as one of the targets to develop anti-cancer schemes/drugs. Our laboratory therefore focuses on investigating the roles of different metabolic molecules in controlling head and neck cancer tumourigenesis. Recent findings from our group have shown that external challenge (e.g. diabetic environment) as well as intrinsic metabolic gene manipulations could lead to modulations of head and neck cancer malignancy revealing the significant role of imbalanced metabolism during Head and Neck Squamous Cell Carcinomas (HNSCCs) development. The ultimate goal of our research is to understand how cancer cells reprogram cellular metabolism to adapt environmental challenges in hope to establish a useful platform for developing cancer metabolism based anti-cancer compounds or therapeutic strategies.

Several specific questions remain to be addressed in my laboratory:

• To define intrinsic impacts of glucose/lipid/protein/mitochondrial metabolic regulations on head and neck carcinogenesis

Current efforts are put to identify the cellular and molecular basis in HNSCC cells in response to glycolytic, lipogenic and protein metabolic alterations in vitro and in vivo as well as to further correlate metabolic profiles with disease stages in clinic. Furthermore, while it was widely accepted that mitochondrial dysfunction could be a very early event resulting in metabolic shift during caner development, better delineation of cellular and molecular regulations in HNSCC cells upon with various degree of mitochondrial impairment are also emphasized in order to define key initiators/regulators of “metabolic reprogramming” during carcinogenesis.

(2) To explore metabolic identify of HNSCC cancer initiating/stem cells (HNSCC-CICs/HNSCC-CSCs)

In clinic, common therapeutic interventions for HNSCC patients are likely developing drug resistance as the treatment mainly selectively kill high-proliferating HNSCC cells but not quiescent CICs/CSCs. In cellular level, it was well accepted that CICs/CSCs likely impact resistance to conventional treatment modalities and promote tumorigenesis in HNSCCs; nevertheless, the metabolic profile and its role in regulating cellular identity and therapeutic sensitivity of head and neck CICs (HN-CICs) is rarely examined. We therefore also aim to explore the regulatory roles of metabolic molecules in controlling stemness and resistance to clinical treatments in HN-CICs, both in vitro and in vivo. To this end, in vitro analysis for cellular and molecular changes and in vivo examination for xenografic tumor growth capacity of HN-CICs deficient or enforced overexpression for genes associated with metabolic molecules and to examine in vitro therapeutic sensitivity in response to combinational chemo-, radio- and photodynamic therapies are emphasized.

(3) To explore molecular regulators for mitochondrial dynamics in HNSCC cells

The root of cancer remains unknown. Mitochondrial integrity is central to efficient cellular energy production and cell survival in the face of environmental stresses. Over half a century, Warburg proposed a mechanism to explain how mitochondria evolve during the carcinogenic process by hypothesizing that a key event in carcinogenesis is the development of an “injury” to the mitochondrial respiratory machinery, resulting in compensatory increases in glycolytic ATP production. Mitochondrial defects therefore have long been suspected to play a key role in the development of cancer although whether dysfunctional mitochondria server as cause of cancer or merely a result of increased glycolysis is still under debate. One of the main research branches in my laboratory is therefore to better understanding of how the defective mitochondrial genome and mitochondrial activity underlie HNSCC oncogenicity and, maybe more importantly, how the normal mitochondrion turn bad during HNSCC development using various cell models.

Publications

Peer-reviewed papers (*: corresponding author)

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. (SCI)
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. (SCI)
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 (SCI) (#: authors contributed equally) (SCI)
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 (SCI)
14. Yang M-C, Wang D-H, Cherng J-H, Li W-C, Lin P-Y, Hsu W-E, Hsu M-L*. Role of Link N in Modulating Inflammatory Conditions. Journal of Oral & Facial Pain and Headache, 33:114-122. (SCI)
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*. Porcine Neonatal Pancreatic Cell Clusters Maintain Their Multipotency in Culture and After Transplantation. Scientific Reports, 8:8212. (SCI)
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. (SCI)
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. (SCI)
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. (SCI)
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 (SCI)
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. (SCI)
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. (SCI)
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. (SCI)
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. (SCI)
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. (SCI)
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, Dec). 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. (SCI)
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. (SCI)
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. (SCI).
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. (SCI)
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: (SCI)
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 (SCI)
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. (SCI)
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. (SCI)
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. (SCI)
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. (SCI)
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). (SCI)
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. (SCI)
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. (SCI)
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. (SCI)
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. (SCI)
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. (SCI)

Book Chapters (*: corresponding author)

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.

Patent

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

Research Grant Supports (2011-present)