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Mei Wan, Ph.D.

Photo of Dr. Mei Wan, Ph.D.

Professor of Orthopaedic Surgery

Research Interests: The role of TGF-B; signaling in pancreatic cancer development; Signaling mechanisms that govern osteoblast differentiation and bone formation: PTH, LRPP5/6 ...read more

Background

Dr. Mei Wan is a professor of orthopaedic surgery at the Johns Hopkins School of Medicine. Her research focuses on the signaling mechanisms that govern osteoblast differentiation and bone formation. The long-term goal of her research is to determine the mechanisms by which parathyroid hormone (PTH) exerts its actions in bone.

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 is a member of the American Association for Cancer Research, American Society for Bone & Mineral Research and International Chinese Hand Tissue Society. She serves on the editorial boards of The Journal of Bone and Mineral Research, Journal of Orthopedics & Rheumatology and Bone Research.

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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 osteoblast differentiation and bone formation. Specifically, she is trying to clarify how parathyroid hormone (PTH) exerts its effects on osteoblast differentiation and bone formation through incorporating with other key signaling factors such as LRP5/6. Another research interest is to understand the role of TGF-β signaling in pancreatic cancer development.

PTH is a primary regulator of calcium homeostasis and bone metabolism in mammals. The effects of PTH on bone remodeling are complex, as it can exert either anabolic or catabolic effects in vivo, depending on how it is administered. The mechanisms responsible for these effects are not completely understood, despite extensive investigation.

Dr. Wan and her team have identified a novel PTH signaling pathway in which the low-density-lipoprotein-related protein 6 (LRP6), a coreceptor of Wnt, is required for PTH-activated β-catenin signaling. In future studies, they will characterize the mechanisms that lead to LRP6 activation in response to PTH stimulation in osteoblasts and determine whether LRP6 is essential for the anabolic effects of PTH on bone in vivo.

Specifically, they will determine: (1) the role of PTH-induced LRP6 phosphorylation in β-catenin signaling activation in osteoblasts; (2) the requirement of LRP6 in PTH-stimulated osteoblast activities in vitro; and (3) the requirement of LRP6 in the PTH bone anabolic effect in vivo. The information gained through these studies should suggest molecular targets for more effective therapies to combat bone loss and also shed light on the mechanisms though which mutations of LRP6 and LRP5 cause bone disease.

Selected Publications

View all on Pubmed

Wang W, Li C, Pang L, Shi C, Guo F, Chen A, Cao X, Wan M. "Mesenchymal stem cells recruited by active TGFβ contribute to osteogenic vascular calcification." Stem Cells Dev. 2014 Feb 10. [Epub ahead of print]

Zhen G, Wen C, Jia X, Li Y, Crane JL, Mears SC, Askin FB, Frassica FJ, Chang W, Yao J, Carrino JA, Cosgarea A, Artemov D, Chen Q, Zhao Z, Zhou X, Riley L, Sponseller P, Wan M, Lu WW, Cao X. "Inhibition of TGF-β signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis." Nat Med. 2013 Jun;19(6):704-12. doi: 10.1038/nm.3143. Epub 2013 May 19.

Li C, Xing Q, Yu B, Xie H, Wang W, Shi C, Crane JL, Cao X, Wan M. "Disruption of LRP6 in osteoblasts blunts the bone anabolic activity of PTH." J Bone Miner Res. 2013 Oct;28(10):2094-108. doi: 10.1002/jbmr.1962.

Wan M, Li C, Zhen G, Jiao K, He W, Jia X, Wang W, Shi C, Xing Q, Chen YF, Jan De Beur S, Yu B, Cao X. "Injury-activated transforming growth factor β controls mobilization of mesenchymal stem cells for tissue remodeling." Stem Cells. 2012 Nov;30(11):2498-511. doi: 10.1002/stem.1208.

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 Association for Cancer Research
  • American Society for Bone & Mineral Research
  • International Chinese Hand Tissue 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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