Monzur Murshed
Professor, Department of Medicine and Faculty of Dental Medicine and Oral Health Sciences
Principal Investigator; Shriners Hospital for Children, Canada
Research in my laboratory primarily focuses on the genetic regulation of tissue mineralization. Bones and teeth are the tissues where physiologic mineral depositions take place. These mineralized tissues serve important biomechanical functions and also act as a reservoir for essential mineral ions required in vital cellular activities. Soft tissue mineralization, on the other hand, is pathologic, which often leads to debilitating conditions. Mineral deposition in the arterial walls can be a risk factor for many cardiovascular diseases, while such deposits in the joints can cause osteoarthritis - a common chronic joint condition of the elderly in Canada. Our working hypothesis suggests that mineral deposition in a tissue depends on the availability of two key mineral ions calcium and inorganic phosphate, the presence of a suitable mineral scaffolding protein matrix and the extracellular levels of inhibitors that prevent mineral crystal precipitation and growth. We use the power of modern mouse genetics in combination with a range of molecular and cell biology techniques to uncover the novel genetic regulators of tissue mineralization and their mechanisms of action. Revealing these regulators should eventually help identify new therapeutic targets and improve the management of complications associated with abnormal tissue mineralization.
- Transgenic models
- Bone remodelling
- Bone mineralization
- Osteoblastogenesis
- Arterial calcification
21. Specific heterozygous variants in MGP lead to endoplasmic reticulum stress and cause spondyloepiphyseal dysplasia.
Gourgas O, Lemire G, Eaton AL, Alshahrani S, Duker AL, Li J, Carroll RS, Mackenzie S, Nikkel SM, Care4Rare Canada Consortium, Bober MB, Boycott KM, Murshed M.
Nat. Commun. (in press).
20. Prevention of Arterial Elastocalcinosis: Differential Roles of the Conserved Glutamic Acid and Serine Residues of Matrix Gla Protein.
Parashar A, Bak K, Murshed M.
Arterioscler Thromb Vasc Biol. 2022 Jun;42(6):e155-e167.
doi: 10.1161/ATVBAHA.122.317518. Epub 2022 Apr 14.
19. Editorial: Ectopic Mineralization of Tissues: Mechanisms, Risk Factors, Diseases, and Prevention.
Kempf H, Komarova S, Murshed M.
Front Cell Dev Biol. 2021 Oct 25;9:759702.
doi: 10.3389/fcell.2021.759702. eCollection 2021.
18: Keutel Syndrome, a Review of 50 Years of Literature.
Cancela ML, Laizé V, Conceição N, Kempf H, Murshed M.
Front Cell Dev Biol. 2021 Apr 29;9:642136.
doi: 10.3389/fcell.2021.642136. eCollection 2021. Review.
17. Elastin calcification in in vitro models and its prevention by MGP's N-terminal peptide.
Parashar A, Gourgas O, Lau K, Li J, Muiznieks L, Sharpe S, Davis E, Cerruti M, Murshed M.
J Struct Biol. 2021 Mar;213(1):107637.
doi: 10.1016/j.jsb.2020.107637. Epub 2020 Oct 12.
16. In vitro and in vivo investigation of osteogenic properties of self-contained phosphate-releasing injectable purine-crosslinked chitosan-hydroxyapatite constructs.
Jahan K, Manickam G, Tabrizian M, Murshed M.
Sci Rep. 2020 Jul 14;10(1):11603.
doi: 10.1038/s41598-020-67886-7.
15. Role of SMPD3 during Bone Fracture Healing and Regulation of Its Expression.
Manickam G, Moffatt P, Murshed M.
Mol Cell Biol. 2019 Feb 4;39(4). pii: e00370-18.
doi: 10.1128/MCB.00370-18. Print 2019 Feb 15.
14. Mechanism of Bone Mineralization.
Murshed M.
Cold Spring Harb Perspect Med. 2018 Dec 3;8(12). pii: a031229.
doi: 10.1101/cshperspect.a031229. Review. Erratum in: Cold Spring Harb Perspect Med. 2020 Aug 3;10(8).
13. In vitro comparison of two titanium dental implant surface treatments: 3M™ESPE™ MDIs versus Ankylos®.
Dhaliwal JS, Marulanda J, Li J, Alebrahim S, Feine JS, Murshed M.
Int J Implant Dent. 2017 Dec;3(1):27.
doi: 10.1186/s40729-017-0083-5. Epub 2017 Jun 27.
12. Matrix Gla protein deficiency impairs nasal septum growth, causing midface hypoplasia.
Marulanda J, Eimar H, McKee MD, Berkvens M, Nelea V, Roman H, Borrás T, Tamimi F, Ferron M, Murshed M.
J Biol Chem. 2017 Jul 7;292(27):11400-11412.
doi: 10.1074/jbc.M116.769802. Epub 2017 May 9.
11. Smpd3 Expression in both Chondrocytes and Osteoblasts Is Required for Normal Endochondral Bone Development.
Li J, Manickam G, Ray S, Oh CD, Yasuda H, Moffatt P, Murshed M.
Mol Cell Biol. 2016 Aug 12;36(17):2282-99.
doi: 10.1128/MCB.01077-15. Print 2016 Sep 1.
10. Sphingolipid metabolism and its role in the skeletal tissues.
Khavandgar Z, Murshed M.
Cell Mol Life Sci. 2015 Mar;72(5):959-69.
doi: 10.1007/s00018-014-1778-x. Epub 2014 Nov 26. Review.
9. Inducible transient expression of Smpd3 prevents early lethality in fro/fro mice.
Alebrahim S, Khavandgar Z, Marulanda J, Murshed M.
Genesis. 2014 May;52(5):408-16.
doi: 10.1002/dvg.22765. Epub 2014 Mar 13.
8. Mechanisms of vascular calcification and associated diseases.
Marulanda J, Alqarni S, Murshed M.
Curr Pharm Des. 2014;20(37):5801-10. Review.
7. Prevention of arterial calcification corrects the low bone mass phenotype in MGP-deficient mice.
Marulanda J, Gao C, Roman H, Henderson JE, Murshed M.
Bone. 2013 Dec;57(2):499-508.
doi: 10.1016/j.bone.2013.08.021. Epub 2013 Aug 28.
6. Elastin haploinsufficiency impedes the progression of arterial calcification in MGP-deficient mice.
Khavandgar Z, Roman H, Li J, Lee S, Vali H, Brinckmann J, Davis EC, Murshed M.
J Bone Miner Res. 2014 Feb;29(2):327-37.
doi: 10.1002/jbmr.2039.
5. A cell-autonomous requirement for neutral sphingomyelinase 2 in bone mineralization.
Khavandgar Z, Poirier C, Clarke CJ, Li J, Wang N, McKee MD, Hannun YA, Murshed M.
J Cell Biol. 2011 Jul 25;194(2):277-89.
doi: 10.1083/jcb.201102051.
4. Lithium chloride attenuates BMP-2 signaling and inhibits osteogenic differentiation through a novel WNT/GSK3- independent mechanism.
Li J, Khavandgar Z, Lin SH, Murshed M.
Bone. 2011 Feb;48(2):321-31.
doi: 10.1016/j.bone.2010.09.033. Epub 2010 Oct 12.
3. Molecular determinants of extracellular matrix mineralization in bone and blood vessels.
Murshed M, McKee MD.
Curr Opin Nephrol Hypertens. 2010 Jul;19(4):359-65.
doi: 10.1097/MNH.0b013e3283393a2b. Review.
2. Unique coexpression in osteoblasts of broadly expressed genes accounts for the spatial restriction of ECM mineralization to bone.
Murshed M, Harmey D, Millán JL, McKee MD, Karsenty G.
Genes Dev. 2005 May 1;19(9):1093-104. Epub 2005 Apr 15.
1. Extracellular matrix mineralization is regulated locally; different roles of two gla-containing proteins.
Murshed M, Schinke T, McKee MD, Karsenty G.
J Cell Biol. 2004 Jun 7;165(5):625-30.