School of Dental Medicine - University at Buffalo

Yang, Shuying (Sheri) M.D., Ph.D. Assistant Professor, Department of Oral Biology

Address:

B36a Foster Hall

Buffalo, NY 14214

(716)829-6338

sy47@buffalo.edu

Research Profile

1. The mechanism of bone resorpton and bone formation and osteoimmunology
2. Gene therapy and stem cell mediated periodontal and craniofacial bone regeneration

Most adult skeletal diseases are due to excess osteoclastic activity, leading to an imbalance in bone remodeling which favors resorption. Such diseases would include osteoporosis, periodontal disease, rheumatoid arthritis, multiple myeloma and metastatic cancers. Therefore, understanding the molecular mechanisms of osteoclast and osteoblast differentiation and activation is critical for successful treatment of these diseases. Our research focuses on identifying the role and mechanism of novel or known genes in bone-related signal pathways and understanding how these genes regulate bone formation and bone resorption by using gene knockout technology. We are also working on gene therapy and stem cell mediated periodontal and craniofacial bone regeneration.

The role and molecular mechanism of novel or known genes in bone formation and resorption
1. By using a genome-wide screening, RNAi and gene knockout technology, we have identified several genes which are closely related to osteoclast differentiation and bone resorption, such as Cathepsin K, RGS10 and RGS12. By generating RGS10 conventional knockout mice, we found that RGS10 plays critical role in osteoclast differentiation; and the RGS10-/- mice exhibited severe osteopetrosis and the impaired osteoclast differentiation. RGS10 is critical regulator in RANKL- Ca2+/calmodulin –PLCr- [Ca2+]i oscillations-NFATc1 pathway. We are generating RGS10 inducible knockout mice to further analyze the role the mechanism of this gene in pathologic age-related bone loss.
2. We have successfully generated RGS12 conditional knockout mice, and are analyzing the role and mechanism of this gene in osteoclast differentiation and bone remodeling.
3. We have screened and identified several new genes that affect bone development and remodeling. We are investigating the role and mechanism of those genes in osteoclast and/or osteoblast differentiation and activation by performing RNAi silence and gene overexpression in vitro and generating gene knockout mice in vivo.

Gene therapy and stem cell s mediate d periodontal and craniofacial bone regeneration
We have established a standardized system for assessing the osteogenic activity of BMP gene transduced mouse embryonic fibroblast by using adenovirus system in mice. We found exploited the potential of gene therapy to express combinations of interacting genes. We examined the ability of combinations of adenoviruses expressing BMP2, 4, 7 and RUNX2 in fibroblast cells and mesenchymal stem cells.
Additional studies are focusing on:
1. Identifying and developing new tissue engineering biomaterials and scaffolds in animal models.
2. Developing novel genetically modified stem cell mediated bone constructs for periodontal and craniofacial bone regeneration
3. Using animal models to assess short- and long-term function of engineered bone tissue constructs in vivo

Representative Publications Search Publications in MEDLINE

Soltanoff CS, Yang S, Chen W, Li YP. Signaling Networks that Control the Lineage Commitment and Differentiation of Bone Cells. Crit Rev Eukaryot Gene Expr. 2009; 19(1):1-46.

Shuying Yang, Yi-Ping Li. RGS10 null mutation impairs osteoclast differentiation resulting from the loss of [Ca2+]i oscillation regulation. Genes & development. 2007 Jul 15; 21(14):1803-16.

Shuying Yang, Wei Chen, Philip Stashenko, Yi-Ping Li. RGS10A is a critical component in the RANKL-evoked signaling pathway for osteoclast differentiation. Journal of Cell Science. 2007 Oct 1; 120(Pt 19):3362-71.

Shuying Yang, Yi-Ping Li. RGS12 Is Essential for Signaling by RANKL for Terminal Differentiation of Osteoclasts. Journal of Bone and Mineral Research. 2007; 22(1):45-54.

Wei Chen, Shuying Yang, Yoke Abe, et al. Cathepsin K knockout mice with a pycnodysostotic phenotype reveal novel function of Cathepsin K as a regulator of osteoclast survival. Human Molecular Genetics, 2007 Feb 15;16(4):410-23.

Huang W, Yang S, Shao J, and Li Y-P. Osteoblast differentiation and gene regulation. Frontiers in Bioscience. 2007 May 1;12:3068-92

Suttatip Kamolmatyakul, Wei Chen, Shuying Yang, et al. IL-1 Up regulates Cathepsin K Gene Expression in Osteoclast Cells in vitro via the Tyrosine Kinase-NFkB pathway. Journal of Dental Research, 2004; 83(10):791-796.

Franceschi RT, Yang S, Rutherford RB, Krebsbach PH, Zhao M, Wang D. Gene therapy approaches for bone regeneration. Cells Tissues Organs. 2004; 176(1-3):95-108.

Shuying Yang, Daoyan Wei, Dian Wang, Mattabltorn Phimphilai, Pual H Krebsbalh, Franceschi RT. In vitro and in vivo synergistic interaction between the Runx2/Cbfa1 transcription factors and bone morphogenetic protein-2 in stimulating osteoblast differentiation. Journal of Bone and Mineral Research, 2003, 18: 705-715.

Renny T Franceschi, Guozhi Xiao, Di Jiang, Raiaram Gopalakrishnan, Shuying Yang, and Elizabeth Reith. Multiple signaling pathways converge on the Cbfa1/Runx2 transcription factor to regulate osteoblast differentiation. Connective Tissue Research, 44 (suppl. 1): 109-116, 2003.

Yang SY, Duan FL, Pan W, et al. Co-expression of TNF-alpha, IFN-beta gene controlled by HLA-B7 promoter enhances antitumor effect. Chin J Microbio & Immu, 2003, 23(4): 275-279.

Yang SY, Duan FL, Lu FM, et al. Comparative study on in vivo direct intratumal gene transfer cationic liposome-TK and nude HSV-TK gene in mice, Chin J Gastroenter & Hapato, 2002, 11 (1): 42-45.