助理教授 - 張婷菡

造釉細胞瘤是顎骨常見的良性齒源性上皮腫瘤，具有局部侵犯性和高復發率，至今，我們仍不清楚其發病和復發機制，為降低腫瘤復發，採以廣泛性顎骨切除，但如此亦降低病人的口腔功能和生活品質。我們之前發現造釉細胞瘤中的LGR5類幹細胞代表一群上皮細胞間質轉化(epithelial-mesenchymal transition, EMT)之中間細胞，可以抵抗BRAFV600E抑制劑而再生腫瘤類器官，且腫瘤間質細胞可以促進上皮幹細胞和EMT的特性。胚胎幹細胞藉由二價組織蛋白修飾，快速因應環境改變而表達或關閉基因，部分癌症也發現類似的調控。然而，目前對於腫瘤微環境是否透過表觀遺傳學調控LGR5造釉細胞瘤幹細胞，進而抵抗治療仍不清楚。本實驗室將探討腫瘤微環境如何透過表觀遺傳學來調控LGR5造釉細胞瘤幹細胞，界定調控腫瘤幹細胞之間質細胞分泌組的主要成分，並透過單細胞定序結合表觀基因組學，解析間質細胞分泌組對於LGR5幹細胞的二價染色質和染色質開放性之調控，並建立病人衍生之類器官和動物模型以助深入了解造釉細胞瘤發病和復發的機制。

期刊論文（*通訊作者，＃共同作者）

1. TH Chang, R Shanti, Y Liang, J Zeng, S Shi, F Alawi, L Carrasco, Q Zhang, and A. D. Le. LGR5+ epithelial tumor stem-like cells generate a 3D-organoid model for ameloblastoma. Cell death and disease. 2020 May 7;11(5):338. IF: 5.959

2. CM Jiang, QZ Zhang, R.M. Shanti, SH Shi, TH Chang, L Carrasco, F Alawi, A.D. Le. Mesenchymal Stromal Cell-derived IL-6 Promotes Epithelial-mesenchymal Transition and Acquisition of Epithelial Stem-like Cell Properties in Ameloblastoma Epithelial Cells. Stem Cells. 2017 Sep;35(9):2083-2094. IF: 5.614

3. QL Xu, A Furuhashi, QZ Zhang, CM Jiang, TH Chang, and A.D. Le. Induction of Salivary Gland–Like Cells from Dental Follicle Epithelial Cells. J Dent Res. 2017 Aug;96(9):1035-1043. IF: 5.125

4. Ting-Han Chang, Da-Yo Yuh, Yung-Tsan Wu, Wan-Chien Cheng, Fu-Gong Lin, Yi-Shing Shieh, Earl Fu, Ren-Yeong Huang. The association between temporomandibular disorders and joint hypermobility syndrome: a nationwide population-based study. Clinical Oral Investigations. 2015;19:2123–2132. IF=2.453

5. Da-Yo Yuh, Ting-Han Chang, Ren-Yeong Huang, Wu-Chien Chien, Fu-Gong Lin, Earl Fu. The National-Scale Cohort Study on Bisphosphonate-Related Osteonecrosis of the Jaw in Taiwan. Journal of Dentistry. 2014;42:1343-1352. IF=3.28