Biomedical Research Education & Training
Faculty Member

Elefteriou, Xiangli Y., Ph.D.
Assistant Professor of Medicine
Assistant Professor of Pharmacology

Lab Url: http://bonecenter.mc.vanderbilt.edu/yang/

Phone Number: 615 322 8052

Email Address: xiangli.yang@vanderbilt.edu

Elefteriou, Xiangli's picture
Academic history
Bachelor of Science, Guangxi Normal University
Master of Science, Mississippi State University
Doctor of Philosophy, University of Alabama at Birmingham
Postdoctoral Research Associate, Baylor College of Medicine

Office Address   Mailing Address

1225F MRB IV

1225F MRB4 37232-6602


Research Keywords
mesenchymal stem cells, osteoblasts, chondrocytes, cartilage, bone, cancer, development, proliferation, differentiation, osteoporosis, dwarfism, fracture, genetics, and cell signaling ,Cancer,Developmental biology,Gene regulation,Genetics,Molecular medicine,Mouse,Signal transduction,Stem cells

Research Specialty
Mouse genetic models as a tool to study human skeletal diseases, such as dwarfism, osteoporosis, and fracture. Cell and molecular biology, Gene transcription regulation, protein-protein interaction, DNA and RNA biochemistry, major signaling pathways, such as BMP, TGF, and Wnt-signaling, regulation of cell fate determination, proliferation, differentiation, and survival.

Research Description
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 diseases. We use osteoblasts, the bone forming cells, chondrocytes, cartilage forming cells, cancer cells, the as model systems to understand how the program of cell proliferation and differentiation are controlled at the transcription level. Osteoblasts and chondrocytes are originated from the same mesenchymal progenitors which also differentiate into a variety of other 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, several essential osteoblast-specific factors have been identified. Recently, we have identified ATF4, another transcription factor that is essential for terminal osteoblast differentiation. 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 ATF4i??s function.

Publications
Campbell, JP, Karolak, MR, Ma, Y, Perrien, DS, Masood-Campbell, SK, Penner, NL, Munoz, SA, Zijlstra, A, Yang, X, Sterling, JA, Elefteriou, F. Stimulation of host bone marrow stromal cells by sympathetic nerves promotes breast cancer bone metastasis in mice. PLoS Biol, 10(7), e1001363, 2012 PMCID:3398959

Lian, N, Lin, T, Liu, W, Wang, W, Li, L, Sun, S, Nyman, JS, Yang, X. Transforming growth factor ?? suppresses osteoblast differentiation via the vimentin activating transcription factor 4 (ATF4) axis. J Biol Chem, 287(43), 35975-84, 2012

Wang, W, Lian, N, Ma, Y, Li, L, Gallant, RC, Elefteriou, F, Yang, X. Chondrocytic Atf4 regulates osteoblast differentiation and function via Ihh. Development, 139(3), 601-11, 2012

Zhuang, J, Zhang, J, Lwin, ST, Edwards, JR, Edwards, CM, Mundy, GR, Yang, X. Osteoclasts in Multiple Myeloma Are Derived from Gr-1+CD11b+Myeloid-Derived Suppressor Cells. PLoS One, 7(11), e48871, 2012

Elefteriou, F, Yang, X. Genetic mouse models for bone studies--strengths and limitations. Bone, 49(6), 1242-54, 2011

Ma, Y, Nyman, JS, Tao, H, Moss, HH, Yang, X, Elefteriou, F. I?2-Adrenergic receptor signaling in osteoblasts contributes to the catabolic effect of glucocorticoids on bone. Endocrinology, 152(4), 1412-22, 2011 PMCID:3103184

Wang, W, Nyman, JS, Ono, K, Stevenson, DA, Yang, X, Elefteriou, F. Mice lacking Nf1 in osteochondroprogenitor cells display skeletal dysplasia similar to patients with neurofibromatosis type I. Hum Mol Genet, 20(20), 3910-24, 2011 PMCID:3177652

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

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

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

Mundy, GR, Yang, X. Hedgehog coordination of postnatal osteoclast and osteoblast activities. Dev Cell, 14(5), 637-8, 2008

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. Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature, 434(7032), 514-20, 2005

Xiao, G, Jiang, D, Ge, C, Zhao, Z, Lai, Y, Boules, H, Phimphilai, M, Yang, X, Karsenty, G, Franceschi, RT. Cooperative interactions between activating transcription factor 4 and Runx2/Cbfa1 stimulate osteoblast-specific osteocalcin gene expression. J Biol Chem, 280(35), 30689-96, 2005

Bialek, P, Kern, B, Yang, X, Schrock, M, Sosic, D, Hong, N, Wu, H, Yu, K, Ornitz, DM, Olson, EN, Justice, MJ, Karsenty, G. A twist code determines the onset of osteoblast differentiation. Dev Cell, 6(3), 423-35, 2004

Vega, RB, Matsuda, K, Oh, J, Barbosa, AC, Yang, X, Meadows, E, McAnally, J, Pomajzl, C, Shelton, JM, Richardson, JA, Karsenty, G, Olson, EN. Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis. Cell, 119(4), 555-66, 2004

Yang, X, Karsenty, G. ATF4, the osteoblast accumulation of which is determined post-translationally, can induce osteoblast-specific gene expression in non-osteoblastic cells. J Biol Chem, 279(45), 47109-14, 2004

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. ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology; implication for Coffin-Lowry Syndrome. Cell, 117(3), 387-98, 2004

Cui, CB, Cooper, LF, Yang, X, Karsenty, G, Aukhil, I. Transcriptional coactivation of bone-specific transcription factor Cbfa1 by TAZ. Mol Cell Biol, 23(3), 1004-13, 2003 PMCID:140696

Sellak, H, Yang, X, Cao, X, Cornwell, T, Soff, GA, Lincoln, T. 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(4), 405-12, 2002

Yang, X, Karsenty, G. Transcription factors in bone: developmental and pathological aspects. Trends Mol Med, 8(7), 340-5, 2002

Yang, X, Cao, X. Smad interactors in bone morphogenetic protein signaling. Methods Mol Biol, 177, 163-78, 2001

Bai, S, Shi, X, Yang, X, Cao, X. Smad6 as a transcriptional corepressor. J Biol Chem, 275(12), 8267-70, 2000

Shi, XM, Blair, HC, Yang, X, McDonald, JM, Cao, X. Tandem repeat of C/EBP binding sites mediates PPARgamma2 gene transcription in glucocorticoid-induced adipocyte differentiation. J Cell Biochem, 76(3), 518-27, 2000

Yang, X, Ji, X, Shi, X, Cao, X. Smad1 domains interacting with Hoxc-8 induce osteoblast differentiation. J Biol Chem, 275(2), 1065-72, 2000

Shi, X, Yang, X, Chen, D, Chang, Z, Cao, X. Smad1 interacts with homeobox DNA-binding proteins in bone morphogenetic protein signaling. J Biol Chem, 274(19), 13711-7, 1999

Ryals, PE, Yang, X. Effects of dichloroisoproterenol on macromolecular synthesis and differentiation in Tetrahymena vorax. J Eukaryot Microbiol, 44(1), 43-5, 1997

Higgins, NP, Yang, X, Fu, Q, Roth, JR. Surveying a supercoil domain by using the gamma delta resolution system in Salmonella typhimurium. J Bacteriol, 178(10), 2825-35, 1996 PMCID:178017

Yang, X, Ryals, PE. Cytodifferentiation in Tetrahymena vorax is linked to glycosyl-phosphatidylinositol-anchored protein assembly. Biochem J, 298 Pt 3, 697-703, 1994 PMCID:1137916


Postdoctoral Position Available
Yes

Postdoctoral Position Details
Studying transcriptional regulation of cell growth and differentiation using genetic models

Updated Date
02/20/2013