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Texas A&M Health Science Center

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Xiaofang Wang

Dr. WangAssistant Professor
Department of Biomedical Sciences
Member of the GSBS Faculty
3302 Gaston Ave.
Dallas, Texas 75246
Phone: 214-828-8436
Fax: 214-874-4538
Email: xwang@bcd.tamhsc.edu
Google Scholar Profile

Education and Post-Graduate Training

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)

Research Interests

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.

Another major research focus of my group is the role of Fam20B, a recently identified xylose kinase essential for the elongation of proteoglycan tetrasaccharide linkage region and the subsequent GAG assembly in tooth morphogenesis.  Through genetically engineered animal models, we have identified striking evidence showing that proteoglycans are involved in the early-stage tooth formation, which opened a new window toward understanding the roles of proteoglycans in the signaling cascades governing tooth development and amelogenesis at both early  and late stages.

These studies will bring new insights into the mechanism underlying the morphogenesis, matrix formation and mineralization in bone and tooth and provide molecular clues for therapeutic strategies for hard-tissue diseases.

Honors and Recognitions

  • ASBMR Harold M. Frost Young Investigator Award (the 43rd Sun Valley Workshop on Musculoskeletal Biology in Sun Valley, Idaho, USA, August 4-7, 2013.)
  • Scientific Advisory Board of the Journal of Endodontics
  • Invited Reviewer of Research Grant Council (RGC) Hong Kong

Selected Publications

  1. Wang X,  Liu J, Zhang H, Xiao M, Li J, Yang C, Lin X, Wu Z, Hu L, Kong X. (2003) Novel mutations in the IRF6 gene for Van der Woude syndrome. Human Genetics 113(5):382-386

  2. Wang X, Hao J, Xie Y, Sun Y, Hernandez B, Yamoah A, Prasad M, Zhu Q, Feng JQ, Qin C. (2010) Expression of FAM20C in the osteogenesis and odontogenesis of Mouse. J Histochem Cytochem 58(11):957-967

  3. Sun Y, Prasad M, Gao T, Wang X, Zhu Q, D’Souza R, Feng JQ, Qin C. (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

  4. Zhu Q, Sun Y, Prasad M, Wang X, Yamoah A, Li Y, Feng JQ, Qin C. (2010) Glycosaminoglycan chain of dentin sialoprotein proteoglycan. J Dent Res 89(8):808-812

  5. Sun Y, Lu Y, Chen S, Prasad M, Wang X, Zhu Q, Zhang J, Ball H, Feng JQ, Butler WT, Qin C. (2010) Key proteolytic cleavage site and full-length form of DSPP. J Dent Res 89(5):498-503

  6. Sun Y, Gandhi V, Prasad M, Yu W, Wang X, Zhu Q, Feng JQ, Hinton RJ, QinC. (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

  7. 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

  8. Zhao J, Tian Y, Xu J, Liu D, Wang X, Zhao B. (2011) Endurance exercise is a leptin signaling mimetic in hypothalamus of Wistar rats. Lipids Health Dis 2(10):225

  9. Wang X, Wang S, Li C, Gao T, Liu Y, Rangiani A, Sun Y, Hao J, George A, Lu Y, Groppe J, Yuan  B, Feng F, QinC. (2012) Inactivation of a novel FGF23 regulator, FAM20C, leads to hypophosphatemic rickets in mice. PLoS Genetics 8(5): e1002708. (Cover story of May issue)

  10. Zhu Q, Prasad M, Kong H, Lu Y, Sun Y, Wang X, Yamoah A, Feng JQ, Qin C. (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

  11. Zhu Q, Gibson MP, Liu Q, Liu Y, Lu Y, Wang X, Feng JQ, Qin C. (2012) Proteolytic processing of dentin sialophosphoprotein (DSPP) Is essential to dentinogenesis. J Biol Chem 287(36):30426-30435.

  12. Wang X, Wang S, Lu Y, Gibson MP, Liu y, Yuan B, Feng JQ, QinC. (2012) FAM20C plays an essential role in the formation of murine teeth. J Biol Chem 287(43):35934-35942.

  13. 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.

  14. Gibson MP, Liu Q, Zhu Q, Lu Y,  Jani P,  X Wang, Liu Y, Paine ML, Snead ML, Feng JQ, Qin C. (2013) Role of NH2-terminal fragment of dentin sialophosphoprotein (DSPP) in dentinogenesis. Eur J Oral Sci 121(2):76-85

  15. Gibson MP, Zhu Q, Wang S, Liu Q, Liu Y, Wang X, Yuan B, Ruest LB, Feng JQ, D’Souza R, Qin C, Lu Y. (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

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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.

  21. Wang X, Wang J, Liu Y, Yuan B, Ruest LB, Feng JQ, Qin C.  The specific role of FAM20C in dentinogenesis.  J Dent Res 2015; 94(2):330-6.

  22.  Du EX, Wang XF, Yang WC, Kaback D, Yee SP, Qin CL, George A, Hao JJ. Characterization of Fam20C expression in odontogenesis and osteogenesis using transgenic mice.  Int J Oral Sci (in press)

Last edited by: jsantacruz 02/17/2015

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