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Xiangli Yang, Ph.D. University of Alabama at Birmingham, Ph.D. |
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| Phone: Fax: Email: |
(615) 322-8052 (615) 343-2611 xiangli.yang@vanderbilt.edu |
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Dr. Yang participated in the discovery of ATF4, an osteoblast-specific transcription factor and downstream target of RSK2, a kinase whose mutation causes Lowry-Coffin syndrome. She is the recipient of multiple awards and fellowships honored by Advances in Mineral Metabolism, the American Society of Bone and Mineral Research, the Children's Brittle Bone Foundation, and March of Dimes. She joined the department of Medicine, Division of Clinical Pharmacology in August 2006. Prior to this, she is an assistant professor of Cellular and Structural Biology Department at University of Texas Health Science Center at San Antonio. |
Our laboratory is interested in regulatory mechanisms governing the process of cell fate determination, with a focus on the identification of novel transcription factors that control osteoblast differentiation and adaptation in response to bone diseases. We use osteoblasts, the bone forming cells, as a model to understand how the program of cell differentiation is controlled at the transcription level. Osteoblasts are originated from mesenchymal progenitors which also differentiate into a variety of cell types, each of which expressing distinct sets of genes controlled by different transcription factors and extracellular signals. By performing loss-of-function experiments in vivo, two essential osteoblast-specific factors, Runx2 and Osterix, have been identified. Recently, we have identified ATF4, another transcription factor that is essential for terminal osteoblast differentiation and function. Deletion of Atf4 in mice leads a severe osteoporosis due to a lack of mature osteoblasts in both embryos and adults and a decrease in the synthesis of Type I collagen, the main constituent of bone matrix protein. We are currently using a variety of approaches to define the mechanisms by which ATF4 governs the terminal osteoblast differentiation and to identify regulatory proteins with which it interacts. ATF4 is also the target for several signal transduction cascades that induce and repress osteoblast differentiation. We are investigating how ATF4 may respond to various extracellular signals through phosphorylation and other types of post-translational modification and the role of these events in the control of ATF4’s function. |
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Recent Publications: Xiao G, Jiang D, Ge C, Zhao Z, Lai Y, Boules H, Phimphilai M, Yang X., Karsenty G, Franceschi RT. (2005) Cooperative interactions between ATF4 and Runx2/Cbfa1 stimulate osteoblast-specific osteocalcin gene expression. J Biol Chem. 280, 30689-30696. PMID: 16000305 Elefteriou, F., Deok, A.J., Takeda, S., Starbuck, M., Yang, X., Liu, X., Kondo, H., Richards, W. G., Bannon, T. W., Noda, M., Clement, K., Vaisse, C., Karsenty, G. (2005) Leptin regulation of bone resorption via the sympathetic nervous system and CART. Natue (in Press). PMID: 15724149 Vega, R., Matsuda, K., Oh, J., Barbosa, A., Yang, X., Meadows, E., McAnally, J., Pomajzl, C., Shelton, J., Richardson, J. A., Karsenty, G., & Olson, E. N. (2004) Histone Deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis. Cell 119, 555-566. PMID: 15537544 Yang, X. & Karsenty, G. (2004) ATF4 whose osteoblast accumulation is determined post-translationally can induce osteoblast-specific gene expression in non-osteoblasts. J. Biol. Chem. 279, 47109-47114.PMID: 15377660 Yang, X., Matsuda, K., Bialek, P., Jacquot, S., Masuoka, HC., Schinke, T., Li, L. Townes, TM., Hanauer,A., and Gerard Karsenty (2004). ATF4, an essential regulator of osteoblast biology, is a substrate of RSK2: implications for Coffin-Lowry Syndrome. Cell 117, 387-398. PMID: 15109498 Bialek, P., Kern, B., Yang, X., Schrock, M., Sosic, D, Hong, N., Wu, H., Yu, K., Ornitz, D.M., Olson, E.N., Justice, M.J. & Karsenty, G. (2004). A Twist code determines the onset of osteoblast differentiation. Dev. Cell 6: 423-435. PMID: 15030764 Cui, C., Cooper, LF, Yang, X., Karsenty, G., and Aukhil, I. (2003). Transcriptional Coactivation of Bone-Specific Transcription Factor Cbfa1 by TAZ. Mol. Cell Biol. 23:1004-1013. Yang, X. and Karsenty, G. (2002) Transcription factors in bone: developmental and pathological aspects. Trends Mol. Med. 8:340-345. Review. Sellak, H., Yang, X., Cao, X., Cornwell, T., Soff, G.A., Lincoln, T. (2002) Sp1 transcription factor as a molecular target for nitric oxide-- and cyclic nucleotide--mediated suppression of cGMP-dependent protein kinase-Ialpha expression in vascular smooth muscle cells. Circ. Res. 90:405-412. Yang, X., Cao, X. (2001). Smad interactors in bone morphogenetic protein signaling Methods. Mol Biol. 177:163-178. Bai, S., Shi, X., Yang, X., and Cao, X. (2000). Smad6 as a transcriptional corepressor. J. Biol. Chem. 275:8267-8270. Yang, X., Ji, X., Shi, X., and Cao, X. (2000). Smad1 domains interacting with Hoxc-8 induce osteoblast differentiation. J. Biol. Chem. 275:1065-1072. Shi, X., Blair, H.C., Yang, X., McDonald, J. M., and Cao, X. (2000). Tandem repeat of C/EBP binding sites mediates PPARg2 gene transcription in glucocorticoid-induced adipocyte differentiation. J. Cell Biochem. 76:518-527. Shi, X., Yang, X., Chen, D, Chang, Z., and Cao, X. (1999). Smad1 interacts with homeobox DNA-binding proteins in bone morphogenetic protein signaling. J. Biol. Chem. 274:13711-13717. |
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