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Yan Zhang M.D., Ph.D.

Regeneration of ameloblast lineage cells from human non-dental epithelial cells

Yan Zhang M.D., Ph.D.

Oral epithelium derived dental epithelial cells go through multiple developmental stages to differentiate into ameloblasts, which are responsible for enamel formation.  Enamel is the hardest mineralized tissue in our body, and the main line of defense for dental decay. Enamel cannot regenerate itself since ameloblasts commit apoptosis when teeth erupt. My research has been focusing on bioengineering functional human ameloblasts from accessible human non-dental epithelial cells, which aims to fill the gap of lack of a cell source for enamel tissue bioengineering and eventually tooth repairing. We are aiming to use transcription factors that we have identified to reprogram adult dental mesenchyme and enhance its instructive potential in driving the differentiation of recombined non-dental epithelial cells. In another parallel effort, we are using  transcription regulators that are critical for enamel formation to directly transdifferentiate human non-dental epithelial cells. 

Selected publications:

Zhang Y, Lu H, Dazin P, Kapila YL. Functional differences between the integrin α4 and integrins α5/αv modulate the motility of human oral squamous carcinoma cells in response to the V region and Heparin-binding domain of fibronectin. Experimental Cell Research. 2004, 295(1):48-58.

Zhang Y, Lu H, Dazin P, Kapila YL. Squamous cell carcinoma cell aggregates escape suspension-induced, p53-mediated anoikis: fibronectin and integrin alphav mediate survival signals through focal adhesion kinase. Journal of Biological Chemistry. 2004, 279(46): 48342-48349.

Zhang Y, Yan QM, Li W, DenBesten PK. Fluoride down-regulates the expression of matrix metalloproteinase 20 in human fetal tooth ameloblast-lineage cells in vitro. European Journal of Oral Science. 2006 May; 114Suppl 1:105-110.

Zhang Y, Li W, Chi HS, Chen J, DenBesten PK. JNK/c-Jun signaling pathway mediates the fluoride-induced down-regulation of MMP-20 in vitro. Matrix Biology, 2007 Oct;26(8):633-41.

Le TQ, Zhang Y, Li W, DenBesten PK. The effect of LRAP on enamel organ epithelial cell differentiation. Journal of Dental Research. 2007 Nov;86(11):1095-9.

He P, Zhang Y (Co-first author), Kim SO, Radlanski RJ, Butcher K, Schneider RA, Denbesten PK. Ameloblast differentiation in the human developing tooth: Effects of extracellular matrices. Matrix Biol. 2010, June, 29(5), 411-419.

Zheng L, Zhang Y, He P, Kim J, Schneider RA, Bronckers AL, Lyaruu DM and DenBesten PK. NBCe1 in mouse and human ameloblasts may be indirectly regulated by fluoride. Journal of Dental Research. 2011, June,90(6), 782-787.

Zhang Y, Kim SO, Vital SO, Ho S, Souron JB, Kim C, Giles K and DenBesten PK. Multiple effects of the cellular prion protein in tooth development. International Journal of Developmental Biology. International Journal of Developmental Biology. 2011, 55 (10-12): 953-960.

Zheng LW, Linthicum L, Denbesten PK, Zhang Y. The similarity between human embryonic stem cell-derived epithelial cells and ameloblast-lineage cells. International Journal of Oral Science. 2013, April, 5(1):1-6.

Zheng LW, Warotayanont R, Stahl J, Kunimatsu R, Klein O, Denbesten PK, Zhang Y. Inductive ability of human developing and differentiated Dental Mesenchyme.  Cells Tissues Organs. July 30, 2013. DOI: 10.1159/000353116