Xiangli Yang
Last active: 2/19/2015

Profile

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 ATF4�s function.

Publications

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. FGFR1 signaling in hypertrophic chondrocytes is attenuated by the Ras-GAP neurofibromin during endochondral bone formation. Karolak MR, Yang X, Elefteriou F (2015) Hum Mol Genet 24(9): 2552-64
    › Primary publication · 25616962 (PubMed) · PMC4383864 (PubMed Central)
  2. Combined MEK inhibition and BMP2 treatment promotes osteoblast differentiation and bone healing in Nf1Osx -/- mice. de la Croix Ndong J, Stevens DM, Vignaux G, Uppuganti S, Perrien DS, Yang X, Nyman JS, Harth E, Elefteriou F (2015) J Bone Miner Res 30(1): 55-63
    › Primary publication · 25043591 (PubMed) · PMC4280331 (PubMed Central)
  3. The loss of activating transcription factor 4 (ATF4) reduces bone toughness and fracture toughness. Makowski AJ, Uppuganti S, Wadeer SA, Whitehead JM, Rowland BJ, Granke M, Mahadevan-Jansen A, Yang X, Nyman JS (2014) Bone : 1-9
    › Primary publication · 24509412 (PubMed) · PMC3992706 (PubMed Central)
  4. The ras-GTPase activity of neurofibromin restrains ERK-dependent FGFR signaling during endochondral bone formation. Ono K, Karolak MR, Ndong Jde L, Wang W, Yang X, Elefteriou F (2013) Hum Mol Genet 22(15): 3048-62
    › Primary publication · 23571107 (PubMed) · PMC3999379 (PubMed Central)
  5. Osteoclasts in multiple myeloma are derived from Gr-1+CD11b+myeloid-derived suppressor cells. Zhuang J, Zhang J, Lwin ST, Edwards JR, Edwards CM, Mundy GR, Yang X (2012) PLoS One 7(11): e48871
    › Primary publication · 23173040 (PubMed) · PMC3500251 (PubMed Central)
  6. Stimulation of host bone marrow stromal cells by sympathetic nerves promotes breast cancer bone metastasis in mice. Campbell JP, Karolak MR, Ma Y, Perrien DS, Masood-Campbell SK, Penner NL, Munoz SA, Zijlstra A, Yang X, Sterling JA, Elefteriou F (2012) PLoS Biol 10(7): e1001363
    › Primary publication · 22815651 (PubMed) · PMC3398959 (PubMed Central)
  7. Chondrocytic Atf4 regulates osteoblast differentiation and function via Ihh. Wang W, Lian N, Ma Y, Li L, Gallant RC, Elefteriou F, Yang X (2012) Development 139(3): 601-11
    › Primary publication · 22190639 (PubMed) · PMC3252356 (PubMed Central)
  8. Genetic mouse models for bone studies--strengths and limitations. Elefteriou F, Yang X (2011) Bone 49(6): 1242-54
    › Primary publication · 21907838 (PubMed) · PMC3331798 (PubMed Central)
  9. Mice lacking Nf1 in osteochondroprogenitor cells display skeletal dysplasia similar to patients with neurofibromatosis type I. Wang W, Nyman JS, Ono K, Stevenson DA, Yang X, Elefteriou F (2011) Hum Mol Genet 20(20): 3910-24
    › Primary publication · 21757497 (PubMed) · PMC3177652 (PubMed Central)
  10. β2-Adrenergic receptor signaling in osteoblasts contributes to the catabolic effect of glucocorticoids on bone. Ma Y, Nyman JS, Tao H, Moss HH, Yang X, Elefteriou F (2011) Endocrinology 152(4): 1412-22
    › Primary publication · 21266510 (PubMed) · PMC3060633 (PubMed Central)
  11. Atf4 regulates chondrocyte proliferation and differentiation during endochondral ossification by activating Ihh transcription. Wang W, Lian N, Li L, Moss HE, Wang W, Perrien DS, Elefteriou F, Yang X (2009) Development 136(24): 4143-53
    › Primary publication · 19906842 (PubMed) · PMC2781050 (PubMed Central)
  12. Vimentin inhibits ATF4-mediated osteocalcin transcription and osteoblast differentiation. Lian N, Wang W, Li L, Elefteriou F, Yang X (2009) J Biol Chem 284(44): 30518-25
    › Primary publication · 19726676 (PubMed) · PMC2781606 (PubMed Central)
  13. Hedgehog coordination of postnatal osteoclast and osteoblast activities. Mundy GR, Yang X (2008) Dev Cell 14(5): 637-8
    › Primary publication · 18477444 (PubMed)