Department of Biomedical Sciences
Member of the GSBS Faculty
3302 Gaston Ave.
Dallas, Texas 75246
Google Scholar Profile
B.D.S., Fourth Military Medical University School of Dentistry, Xi'an, China (1995)
M.D.S., Fourth Military Medical University School of Dentistry, Xi'an, China (2000)
Ph.D., Fourth Military Medical University (2003) (Dissertation research done at Shanghai Institutes for Biological Sciences, Chinese Academy of Science)
Postdoctoral Fellowship, Department of Oral Biology, Ohio State University, College of Dentistry (2006-2008)
We and other labs have established that FAM20C is a Golgi-enriched kinase phosphorylating the serine residue in S-x-E/pS motifs in a broad spectrum of proteins on the secretory pathway, including the secretory calcium-binding phospho-proteins (SCPP), which comprise matrix proteins critical for bone, dentin, and enamel formation. Loss-of-function mutations in the human FAM20C gene cause Raine syndrome, an osteosclerotic bone dysplasia, while Fam20C knockout mice develop severe hypophosphatemic rickets due to renal phosphate wasting, as well as severe dentin and enamel defects.
My research interests focus on the mechanism underlying the phosphate wasting in the FAM20C-KO mice. We found that a remarkable increase in circulating FGF23, a phosphaturic hormone mediating phosphate homeostasis via the regulation of NaPi2a/c transporters in the proximal tubule of kidney, likely contributes to the increased phosphate excretion. Interestingly, the high-FGF23 and low-phosphate phenotype is shared by loss-of-function mutations in several SIBLING proteins, suggesting an association between the phosphorylation failure of SIBLINGs and the increased FGF23 in the FAM20C-KO mice. Indeed, the serum phosphate level is governed by a complicated network on the bone-kidney-parathyroid axes, including PTH, 1,25 Dihydroxy Vitamin D, FGF23, and NaPi2a/c, etc. The exact mechanism of how these molecules mediate phosphate homeostasis remains largely unknown. My lab will employ FGF23-KO, PTH-KO, and several other genetically engineered mouse models to investigate the mechanisms underlying phosphate wasting in FAM20C-KO mice.
The FAM20C-KO mice also showed severe defects in dentin and enamel. Through conditional knockout strategies, we have established that the enamel and dentin defects are independent from each other, and the hypophosphatemia does not contribute to the enamel defects, ie., the enamel defects are caused by the local effects of FAM20C-inactivation -- the phosphorylation failure of enamel matrix proteins belonging to the SCPP family. Another research interest is to investigate the impact of phosphoserine loss on the biochemical and biophysical behaviors of enamel matrix proteins on enamel matrix assembly and mineralization.
These studies will bring new insights into the mechanism underlying the matrix formation and mineralization in bone and tooth and provide molecular clues for therapeutic strategies for hard-tissue diseases.
X Wang, J Liu, H Zhang, M Xiao, J Li, C Yang, X Lin, Z Wu, L Hu, X Kong. (2003) Novel mutations in the IRF6 gene for Van der Woude syndrome. Human Genetics 113(5):382-386
X Wang, J Hao, Y Xie, Y Sun, B Hernanderz, A Yamoah, M Prasad, Q Zhu, JQ Feng, C Qin. (2010) Expression of FAM20C in the Osteogenesis and Odontogenesis of Mouse. J Histochem Cytochem 58(11):957-967
Y Sun, M Prasad, T Gao, X Wang, Q Zhu, R D’Souza, JQ Feng, C Qin. (2010) Failure to process dentin matrix protein 1 (DMP1) into fragments leads to its loss of function in osteogenesis. J Biol Chem 285(41):31713-31722
Y Sun, V Gandhi, M Prasad, W Yu, X Wang, Q Zhu, JQ Feng, RJ Hinton, C Qin. (2010) Distribution of small integrin-binding ligand, N-linked glycoproteins (SIBLING) in the condylar cartilage of rat mandible. Int J Oral Maxillofac Surg 39(3):272-281
M Prasad, Q Zhu, Y Sun, X Wang, A Kulkarni, A Boski, JQ Feng, C Qin. (2011) Expression of dentin sialophosphoprotein in non-mineralized tissues. J Histochem Cytochem 59(11):1009-1021
X Wang, S Wang, C Li, T Gao, Y Liu, A Rangiani, Y Sun, J Hao, A George, Y Lu, J Groppe, B Yuan, J Feng, C Qin. (2012) Inactivation of a novel FGF23 regulator, FAM20C, leads to hypophosphatemic rickets in mice. PLoS Genetics 8(5): e1002708. (Cover story of May issue)
Q Zhu, M Prasad, H Kong, Y Lu, Y Sun, X Wang, A Yamoah, JQ Feng, C Qin. (2012) Partial Blocking of Mouse DSPP Processing by Substitution of Gly(451)-Asp(452) Bond Suggests the Presence of Secondary Cleavage Site(s). Connect Tissue Res 53(4):307-312
Q Zhu, MP Gibson, Q Liu, Y Liu, Y Lu, X Wang, JQ Feng, C Qin. (2012) Proteolytic Processing of Dentin Sialophosphoprotein (DSPP) Is Essential to Dentinogenesis. J Biol Chem 287(36):30426-30435
X Wang, S Wang, Y Lu, MP Gibson, Y Liu, B Yuan, JQ Feng, C Qin. (2012) FAM20C plays an essential role in the formation of murine teeth. J Biol Chem 287(43):35934-35942
Li C, Xie X, Wang X, Sun Y, Liu P, Chen L, Qin C. (2013) Differential expression and localization of dentin matrix protein 1 (DMP1) fragments in mouse submandibular glands. J Mol Histol. 44(2):231-9.
MP Gibson, Q Liu, Q Zhu, Y Lu, P Jani, X Wang, Y Liu, ML Paine, ML. Snead, JQ Feng, C Qin. (2013) Role of NH2-terminal Fragment of Dentin Sialophosphoprotein (DSPP) in Dentinogenesis. Eur J Oral Sci. 121(2):76-85
MP Gibson, Q Zhu, S Wang, Q Liu, Y Liu, X Wang, B Yuan, LB Reust, JQ Feng, R D’Souza, C Qin, Y Lu. (2013) The rescue of DMP1-deficient tooth defects by the transgenic expression of DSPP indicates that DSPP is a downstream effector molecule of DMP1 in dentinogenesis. J Biol Chem. 288(10):7204-7214
Gibson MP, Jani P, Liu Y, Wang X, Lu Y, Feng JQ, Qin C. (2013). Failure to process dentin sialophosphoprotein into fragments leads to periodontal defects in mice. Eur J Oral Sci. 121(6):545-550
Wang X, Jung J, Liu Y, Yuan B, Lu Y, Feng JQ, Qin C. (2013) The specific role of FAM20C in amelogenesis. J Dent Res 92(11):995-9.
Wang X, Wang J, Yuan B, Lu Y, Feng JQ, Qin C. (2014). Overexpression of Dmp1 fails to rescue the bone and dentin defects in Fam20C knockout mice. Connect Tissue Res. 55(4):299-303
Gibson MP, Jani P, Wang X, Lu Y, Qin C. (2014). Overexpressing the NH2-terminal fragment of dentin sialophosphoprotein (DSPP) aggravates the periodontal defects in Dspp knockout mice. J Oral Biosci. 56(4):143-148.
Liu P, Zhang H, Liu C, Wang X, Chen L, Qin C. (2014). Inactivation of Fam20C in Cells Expressing Type I Collagen Causes Periodontal Disease in Mice. PLoS One. 9(12):e114396
Wang X, Wang J, Liu Y, Yuan B, Ruest LB, Feng JQ, Qin C. The Specific Role of FAM20C in Dentinogenesis. J Dent Res. (in press)