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Mei Wan, Ph.D.

Photo of Dr. Mei Wan, Ph.D.

Professor of Orthopaedic Surgery

Research Interests: parathyroid hormone; LRP6; bone marrow mesenchymal stem/progenitor cells; tissue repair/remodeling; stem cell mobilization

Background

Dr. Mei Wan is a professor of orthopaedic surgery at the Johns Hopkins School of Medicine. Her research focuses on the characterization of the mechanisms by which bone marrow mesenchymal stem/progenitor cells (MSPCs) are regulated in various physiological and pathological conditions such as bone remodeling, skeletal disease/disorders, and vascular repair/remodeling. 

Dr. Wan earned her Ph.D. and M.D. from Hebei Medical University in Shijiazhuang, China. She completed postgraduate training at the University of Alabama at Birmingham. Prior to joining Johns Hopkins, Dr. Wan was an assistant professor of pathology at the University of Alabama at Birmingham.

She serves on the editorial boards of The Journal of Bone and Mineral Research, Journal of Orthopedics & Rheumatology and Bone Research. She has been a regular member of VA Endocrinology-B Merit Review study section since 2012 and served as a reviewer in NIH study sections.

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Titles

  • Professor of Orthopaedic Surgery

Departments / Divisions

Research & Publications

Research Summary

Dr. Wan’s long-term research goal is to understand the signaling mechanisms that govern the lineage fate and functions of bone marrow mesenchymal stem/progenitor cells (MSPCs) in bone remodeling and disorders as well as in tissue repair/ remodeling. Specifically, her research team aims to define the role of parathyroid hormone (PTH)in regulating osteoblastic lineage cells and bone marrow MSPCs. Dr. Wan and her team devised several novel genetic mouse models, which were used to identify the Wnt co-receptor LRP6, as an essential component in PTH-stimulated signaling pathways in osteoblastic lineage cells. She showed that activation of the PTH-type 1 receptor forms a complex with LRP6 upon PTH stimulation, leading to the activation of both β-catenin and cAMP/PKA signaling. This study was the first to link the bone anabolic activity of PTH to the Wnt pathway to PTH.

Mesenchymal stem cells (MSCs) participate in repair/regeneration of many tissues.  However, the key factor(s) or signaling pathways that control the lineage fate of MSCs in target tissue are largely unknown. In recent several years, Dr. Wan have developed a new line of investigation, which is examining MSPCs’ mobilization and homing in settings of vascular injury and disorders. Using rat and mouse models of endovascular mechanical injury of arteries, which recapitulates clinical coronary artery restenosis post balloon angioplasty, her group demonstrated that bone marrow nestin+ MSPCs are mobilized into bloodstream and home to the injured sites to participate in vascular repair/remodeling. Furthermore, her team revealed that RhoA/ROCK signaling determines the lineage specificity of MSCs at the injured tissue by regulating cell-ECM interactions.

Osteoporosis is commonly associated with the population who have developed hyperlipidemia and associated atherosclerosis. It is believed that the same bioactive oxidized lipids (oxlipids) and low-density lipoprotein (oxLDL) that promote atherosclerosis also adversely affect bone. However, how these bioactive lipids act on bone cells remain largely unknown. In future studies, she will determine whether LRP6 on MSPCs is an important molecular mediator of bioactive lipids for their adverse effect on bone and elucidate the underlying mechanisms.

Selected Publications

View all on Pubmed

Li C, Zhen G, Xie L, Crane JL, Farber E, Farber CR, Gao P, Cao X, *Wan M. RhoA Determines Lineage Fate of MSCs by Modulating CTGF-VEGF Complex in Extracellular Matrix. Nature Communications 2016; Apr 29;7:11455. PMID: 27126736

Li C, Wang W, Xie L, Cao X, *Wan M. LRP6 Expression Is Required For PTH-Induced SOST Repression. Ann N Y Acad Sci (Marrow)2016; 1364(1):62-73. PMID: 25847683

Li C, Xing Q, Yu B, Xie H, Wang W, Shi C, Crane JL, Cao X, and *Wan M. Disruption of LRP6 in osteoblasts blunts the bone anabolic activity of PTH. J Bone Mineral Res 2013; 28(10):2094-108. PMID: 23609180

Shi C, Li J, Wang W, Cao W, Cao X, *Wan M. Antagonists of LRP6 Regulate PTH-induced cAMP Generation. Annals of the New York Academy of Sciences 2011; 1237:39-46.PMID: 22082363

Yu B, Zhao X, Yang C, Crane J, Xian L, Lu W, Wan M, Cao X. "Parathyroid hormone induces differentiation of mesenchymal stromal/stem cells by enhancing bone morphogenetic protein signaling." J Bone Miner Res. 2012 Sep;27(9):2001-14. doi: 10.1002/jbmr.1663.

Activities & Honors

Memberships

  • American Heart Association
  • American Society for Bone & Mineral Research
  • Endocrinology Society

Professional Activities

  • Editorial board, The Journal of Bone and Mineral Research
  • Editorial board, Bone Research
  • Editorial board, Journal of Orthopedics & Rheumatology
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