Monzur Murshed

Monzur Murshed, Ph.D.

Associate Professor, Department of Medicine and Faculty of Dentistry
Principal Investigator; Shriners Hospital for Children, Canada
1529 Cedar Avenue, Montreal, QC H3G 1A6, Canada

Tel: 514-282-8255

monzur.murshed [at] mcgill.ca
Website

Biographical Sketch

My training as a matrix biologist started in 1997 in the laboratory of Drs. Roswitha Nischt and Thomas Krieg at the University of Cologne, Germany, where I completed my doctoral thesis on the structure of basal lamina, a specialized extracellular membrane with crucial biological functions.

In early 2001, I joined the laboratory of Dr. Gerard Karsenty, a leading bone biologist at Baylor College of Medicine, Houston, Texas, as a post-doctoral fellow, where I conducted research on the mechanisms of extracellular matrix mineralization. I generated and analyzed several transgenic animal models to characterize the in vivo function of a potent mineralization inhibitor – Matrix Gla protein (MGP). In a separate study, I used a combination of 9 different mouse models and cell culture-based experiments to demonstrate that bone and tooth matrix mineralization can be explained, at least in part, by the unique co-expression of broadly expressed genes. Apart from these projects related to extracellular matrix mineralization, I conducted research on the regulation of bone mass by the parasympathetic nervous system.

After joining McGill University, I continued to pursue my research on the mechanism of extracellular matrix mineralization (ECM) in both 'hard' and 'soft' tissues. At the same time, I took initiatives to expand my research expertise into other areas of bone biology e.g. skeletal development and the regulation of bone remodeling.

Over the past fifteen years, I have been working as an ECM biologist, twelve years of which have been devoted to studying the mechanisms of biomineralization. During this time, I have generated and analyzed many gene-targeted and transgenic animal models relevant to my research. My work is currently funded by CIHR and Heart and Stroke Foundation of Canada.

Keywords

Extracellular matrix mineralization, vascular calcification, bone remodeling, osteoblast biology, genetically modified mouse models, nervous system and regulation of bone mass.

Research or Clinical Activities

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.

Selected Recent Publications

Marulanda M, Gao C, Roman H, Handerson JE, Murshed M. Prevention of arterial calcification corrects the low bone mass phenotype in MGP-deficient mice. Bone. 2013 Aug 28. doi:pii: S8756-3282(13)00336-0. 10.1016/j.bone.2013.08.021.

Khavandgar Z, Roman H, Li J, Lee S, Vali H, Brinckmann J, Davis EC, Davis EC, Murshed M. Elastin haploinsufficiency impedes the progression of arterial calcification in MGP-deficient mice. J Bone Miner Res. 2013 Jul 15. doi: 10.1002/jbmr.2039.

Khavandgar Z, Alebrahim S, Eimar H, Tamimi F, McKee MD and Murshed M. Local Regulation of Tooth Mineralization by Sphingomyelin Phosphodiesterase 3. J Dent Res. 2013 Apr; 92(4):358-64.

Khavandgar Z, Poirier C, Clarke CJ, Li J, Wang N, McKee MD, Hannun YA and Murshed M. A Cell-Autonomous Requirement for Neutral Sphingomyelinase 2 in Bone Mineralization. J Cell Biol. 2011 Jul 25; 194(2):277-89.

Li JJ, Khavandgar Z, Lin SH and Murshed M. Lithium chloride attenuates BMP-2 signaling and inhibits osteogenic differentiation through a novel WNT/GSK3- independent mechanism. Bone. 2011 Feb 1;48(2):321-31.

PubMed Publications – M. Murshed