Wen-Cheng Xiong, MD, PhD

Riuko and Archie G. Co Professor
Department of Neurosciences
School of Medicine

Research Information

Research Interests

We are interested in molecular mechanisms underlying neural development, neuro-degeneration, and bone homeostasis. Although neural development, neurodegeneration, and bone homeostasis are three distinct events/processes, there are potential links among these processes. For examples, patients with neurodegenerative disorders, including Alzheimer’s disease (AD) and Parkinson’s disease (PD), frequently have non-cognitive/non-motor related defects. These non-typical symptoms occur earlier in AD/PD patients’ life, thus, they not only impact patients’ quality of life, but also could be predictor for disease progression. We have found that one of these non-typical defects is bone-degenerative-like phenotype. We therefore have invested significant efforts in understanding why and how the non-typical deficits (e.g., bone deficits) are associated with AD/PD. Technically, we have used a combination of biochemical (in vitro), cell biological (in culture), and genetic mutant animal models to address this issue.


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I. Investigating netrin-1 signaling in neural axonal pathfinding.

  1. R. Ren, G-L. Ming, Y. Xie, Y. Hong, D-M. Sun, Z-Q. Zhao, Z. Feng, Q. Wang, S. Shim, Z-F. Chen, H-J. Song, L. Mei, and W.C. Xiong*. Focal adhesion kinase in netrin-1 signaling. Nat. Neurosci., 11: 1204-1212, 2004. PMID: 15494733.
  2. Y. Xie, Y-Q. Ding, Y. Hong, Z. Feng, S. Navarre, C-X. Xi, X-J. Zhu, C-L. Wang, S. L. Ackerman, D. Kozlowski, L. Mei, and W-C Xiong*. Phosphatidylinositol transfer protein α in netrin-1-induced PLC signaling and neurite outgrowth. Nat. Cell Biol., 7:1124-1132, 2005. PMID: 16244667.
  3. X-J. Zhu, C-Z. Wang, P-G. Dai, Y. Xie, N-N. Song, Y. Liu, L. Mei, Y-Q. Ding, and W-C. Xiong*. Myosin X regulates netrin receptor and functions in axonal path-finding. Nat. Cell Biol., 9:184-192, 2007. PMID: 17237772.
  4. Y. Liu, Y. Peng, P-G. Dai, Q-S. Du, L. Mei, and W-C. Xiong*. Differential regulation of myosin X movements by its cargos, DCC and neogenin. J. Cell Sci., 125: 751-762. 2012. PMID: 22349703.

II. Understanding mechanisms underlying neogenin-YAP regulation of BMP signaling and functions.

  1. Z. Zhou, J-X. Xie, D-H. Lee, J-U. Jung, Y. Liu, S. Xiong, L. Mei, and W-C. Xiong*. Neogenin regulation of BMP induced canonical Smad signaling and endochondral bone formation. Dev. Cell, 19:90-102, 2010. PMID: 20643353
  2. D-H. Lee, L-J Zhou, Z. Zhou, J-X. Xie, J-U. Jung, Y. Liu, C-X. Xi, L. Mei, and W-C. Xiong*. Neogenin inhibits HJV secretion and regulates BMP-induced hepcidin expression and iron homeostasis. Blood, 115:3136-3145,2010. PMID: 20065295. (A cover paper)
  3. Z-H. Huang, D. Sun, D-H. Lee, Y. Wang, G. Hu, J-L. Zhou, L. Mei, and W-C. Xiong*. Neogenin promotes cortical astrogliogenesis by increasing BMP2 activation of YAP. J. Neurosci., 36:5833-5849, 2016. PMID: 27225772
  4. Z-H. Huang, Y. Wang, G. Hu, J-L. Zhou, L. Mei*, and W-C. Xiong*. YAP Is a Critical Inducer of SOCS3, Preventing Reactive Astrogliosis. Cerebral Cortex, 26(5):2299-2310, 2016. PMID: 26679195
  5. Z-H. Huang, J-X. Hu, J-X. Pan, Y. Wang, G. Hu, J-L. Zhou, L. Mei, and W-C. Xiong*. YAP stabilizes SMAD1 and promotes BMP2-induced neocortical astrocytic differentiation. Development, 143:2398-2409, 2016. PMID: 27381227

III. Investigating VPS35’s function in the pathogenesis of neuro-degenerative disorders.

  1. L. Wen, F-L. Tang, Y. Hong, S-W. Luo, C-L. Wang, W. He, C-Y. Shen, F. Xiong, J-U. Jung, D-H. Lee, Q-G. Zhang, D. Brann, T-W. Kim, R. Yan, L. Mei, and W-C. Xiong*. Vps35 haploinsufficiency increases Alzheimer’s disease neuropathology. J. Cell Biol., 195:765-779. 2011. PMID: 22105352
  2. C-L. Wang, F-L. Tang, Y. Peng, C-Y. Shen, L. Mei, and W-C. Xiong*. VPS35 regulates developing mouse hippocampal neuron morphogenesis by promoting retrograde trafficking of BACE1. Biolo. Open, 1: 1248-1257, 2012. PMID: 23259059
  3. Y. Tian, F-L. Tang, X-D. Sun, L. Wen, L. Mei, B-S. Tang*, and W-C. Xiong*. Vps35-deficiency results in an impaired AMPA receptor trafficking and decreased dendritic spine maturation in hippocampal neurons. Mol. Brain, 8:70. 2015. PMID: 26521016
  4. F-L. Tang, J. Erion, Y. Tian, W. Liu, D-M. Yin, J. Ye, B-S. Tang, L. Mei, and W-C. Xiong*VPS35 in dopamine neurons is required for endosome-to-Golgi retrieval of LAMP2a, a receptor for chaperone-mediated autophage that is crucial for a-synuclein degradation and prevention of pathogenesis of Parkinson’s disease. J. Neurosci., 35: 10613-10628, 2015. PMID: 26203154
  5. F-L. Tang, J. Erion, W. Liu, J-X. Hu, J. Ye, L. Mei, and W-C. Xiong*. VPS35 deficiency or mutation causes dopaminergic neuronal loss by impairing mitochondrial fusion and function. Cell Rep., 12(10):1631-1643, 2015. PMID: 26321632

IV. Investigating relationship between AD and altered bone metabolism.

  1. Q. Wang, Y. Xie, Q-S. Du, X-J. Wu, X. Feng, L. Mei, J. McDonald, and W-C. Xiong*.  Regulation of the formation of osteoclastic actin rings by PYK2 interacting with gelsolinJ. Cell Biol., 160: 565-575, 2003. PMID: 1258912
  2. Z. Zhou, D. Immel, C-X. Xi, A. Bierhaus, X. Feng, L. Mei, P. Nawroth, D. M. Stern, and W-C. Xiong*.  Regulation of Osteoclast Function and Bone Mass by RAGE. J. Exp. Med., 203: 1067-1080, 2006. PMID: 16606672
  3. S. Cui, F. Xiong, Y. Hong, J-U. Jung, X-S. Li, J-Z. Liu, R. Yan, L. Mei, X. Feng, and W-C. Xiong*. APPswe/Ab regulation of osteoclast activation and RAGE expression in an age dependent manner. J. Bone Min. Res., 26:1084-1098, 2011. PMID: 21542009
  4. W-F. Xia, J-U. Jung, S. Cui, S. Xiong, L. Xiong, X-M. Shi, L., Mei, and W-C. Xiong*. Swedish mutant APP suppresses osteoblast differentiation and causes osteoporotic deficit, which is ameliorated by NAC anti-oxidant. J. Bone Min. Res., 10: 2122-2135, 2013. PMID: 23649480
  5. W-F. Xia, F-L. Tang, L. Xiong, J-U. Jung, S. Xiong, D-H. Lee, X-S. Li, X. Feng, L. Mei, and W-C. Xiong*. Vps35-loss promotes hyper-resorptive osteoclastogenesis and osteoporosis via sustained RANKL signaling. J. Cell Biol., 200 (6):821-837, 2013. PMID: 23509071
  6. L. Xiong, W-F. Xia, F-L. Tang, J-X. Pan, L. Mei, and W-C. Xiong*. Retromer in osteoblasts interacts with PPP1R14C, terminates PTH signaling, and promotes PTH’s catabolic response. EBioMedicine, 9:45-60, 2016. PMID: 27333042
  7. Jin-Xiu Pan, Fulei Tang, Fei Xiong, Lei Xiong, Peng Zeng, Bo Wang, Kai Zhao, Haohan Guo, Cui Shun, Wen-Fang Xia, Lin Mei & Wen-Cheng Xiong*. APP promotes osteoblast survival and bone formation by regulating mitochondrial function and preventing oxidative stressCell Death & Diseasevolume 9, 1077, 2018.

V. Investigating LRP4’s function in bone-homeostasis.

  1. L. Xiong, J. Jung, HT. Wu, W-F. Xia, J-X. Pan, C.Y. Sheng, L. Mei and W.C. Xiong*. LRP4 in osteoblasts suppresses bone formation and promotes osteoclastogenesis and bone resorption. Proc. Nat. Acad. Sci. USA, 112: 3487-3492, 2015. PMID:25733894
  2. L. Xiong, X-D. Sun, J-X. Pan, J-U. Jung, L. Mei, and W.C. Xiong*. Osteoblastic Lrp4 promotes osteoclastogenesis and bone resorption by regulating ATP release and adenosine-A2AR signaling. J. Cell Biol., 216(3):761-778. 2017. PMID: 28193701


Doctor of Philosophy
John Hopkins University