Center for Bone Biology

Xiangli Yang, Ph.D.

University of Alabama at Birmingham, 2000

Assistant Professor, Clinical Pharmacology

Phone:  (615) 322-8052

Fax:  (615) 343-2611

Email:  xiangli.yang@vanderbilt.edu

http://medschool1.mc.vanderbilt.edu/facultydata/php_files/show_faculty.php?id3=16510

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 the National Institutes of Health (NIH), Advances in Mineral Metabolism, the American Society of Bone and Mineral Research, the Children’s Brittle Bone Foundation, and the 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 since 2004.

Research Interest :

Animal model and human diseases
Transcriptional regulation of cell differentiation
Development
Molecular Genetics

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.  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.

Current projects

1.    Identification of novel factors that interact with ATF4 and regulate its potential to control osteoblast differentiation and activity.
2.    ATF4 regulate chondrocyte proliferations and differentiation via target Indian Hedgehog transcription.
3.    PTH and IGF1 exert their anabolic effect on bone formation via regulating the phosphorylation of ATF4.
4.    ATF4 may regulate Sirt1’s activity during osteoblast differentiation and bone formation. 

Funding
 

Techniques

1.    General molecular biology
2.    In situ hybridization
3.    Yeast two hybridization
4.    Protein chemistry including chromatography
5.    Primary osteoblast and chondrocyte isolation
6.    Mouse embryo isolation/Skeletal preparation/histology

Lab personnel

Lingzhen Li, M.S.:  Research Assistant II
Weiguang Wang, M.S.:  Graduate Student, Pharmacology
Na Lian, Ph.D.:  Former Graduate Student of Pharmacology
Xiaodan Wang, M.D., Ph.D.:  Former Postdoc Fellow
Wenguang Liu, Ph.D.:  Post-Doctoral Fellow

Recent Publications:

1. Ma, Y, Nyman, JS, Tao, H, Moss, HH, Yang, X, Elefteriou, F. {beta}2-Adrenergic Receptor Signaling in Osteoblasts Contributes to the Catabolic Effect of Glucocorticoids on Bone. Endocrinology, 2011  PMID:  21266510
2. Wang, W, Nyman, JS, Moss, HE, Gutierrez, G, Mundy, GR, Yang, X, Elefteriou, F. Local low-dose lovastatin delivery improves the bone-healing defect caused by Nf1 loss of function in osteoblasts. J Bone Miner Res, 25(7), 1658-67, 2010  PMID:  20200958 
3. Lian, N, Wang, W, Li, L, Elefteriou, F, Yang, X. Vimentin inhibits ATF4-mediated osteocalcin transcription and osteoblast differentiation. J Biol Chem, 284(44), 30518-25, 2009  PMID:  19726676   
4. Wang, W, Lian, N, Li, L, Moss, HE, Wang, W, Perrien, DS, Elefteriou, F, Yang, X. Atf4 regulates chondrocyte proliferation and differentiation during endochondral ossification by activating Ihh transcription. Development, 136(24), 4143-53, 2009  PMID:  19906842
5. Mundy, G. R. & Yang, X. (2008). Hedgehog coordination of osteoblast and osteoclast activities. Dev. Cell.  PMID: 18477444
6. 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
7. Elefteriou F, Ahn JD, Takeda S, Starbuck M, Yang X, Liu X, Kondo H, Richards WG, Bannon TW, Noda M, Clement K, Vaisse C, Karsenty G. (2005). Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature. 434:514-20. PMID: 15724149
8. Vega RB, Matsuda K, Oh J, Barbosa AC, Yang X, Meadows E, McAnally J, Pomajzl C, Shelton JM, Richardson JA, Karsenty G, Olson EN. (2004). Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis. Cell. 119:555-66. PMID: 15537544
9. Yang X, Karsenty G. (2004). ATF4, the osteoblast accumulation of which is determined post-translationally, can induce osteoblast-specific gene expression in non-osteoblastic cells. J Biol Chem. 279:47109-14. PMID: 15377660
10. Yang X, Matsuda K, Bialek P, Jacquot S, Masuoka HC, Schinke T, Li L, Brancorsini S, Sassone-Corsi P, Townes TM, Hanauer A, Karsenty G. (2004). ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology; implication for Coffin-Lowry Syndrome. Cell. 117:387-98. PMID: 15109498
11. Bialek P, Kern B, Yang X, Schrock M, Sosic D, Hong N, Wu H, Yu K, Ornitz DM, Olson EN, Justice MJ, Karsenty G. (2004). A twist code determines the onset of osteoblast differentiation. Dev Cell. 6:423-35. PMID: 15030764
12. Cui CB, Cooper LF, Yang X, Karsenty G, Aukhil I. (2003). Transcriptional coactivation of bone-specific transcription factor Cbfa1 by TAZ. Mol Cell Biol. 23:1004-13. PMID: 12529404
13. Yang X, Karsenty G. (2002). Transcription factors in bone: developmental and pathological aspects. Trends Mol Med. 8:340-5. Review. PMID: 12114114
14. Sellak H, Yang X, Cao X, Cornwell T, Soff GA, 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. 90:405-12. PMID: 11884369
15. Yang X, Cao X. (2001). Smad interactors in bone morphogenetic protein signaling. Methods Mol Biol. 177:163-78. PMID: 11530605
16. Bai S, Shi X, Yang X, Cao X. (2000). Smad6 as a transcriptional corepressor. J Biol Chem. 275:8267-70. PMID: 10722652
17. Shi XM, Blair HC, Yang X, McDonald JM, Cao X. (2000). Tandem repeat of C/EBP binding sites mediates PPARgamma2 gene transcription in glucocorticoid-induced adipocyte differentiation. J Cell Biochem. 76:518-27. PMID: 10649448
18. Yang X, Ji X, Shi X, Cao X. (2000). Smad1 domains interacting with Hoxc-8 induce osteoblast differentiation. J Biol Chem. 275:1065-72. PMID: 10625647
19. Shi X, Yang X, Chen D, Chang Z, Cao X. (1999) Smad1 interacts with homeobox DNA-binding proteins in bone morphogenetic protein signaling. J Biol Chem. 274:13711-7. PMID: 10224145