Marc D. McKee

Marc D. McKee
Department: 
Anatomy and Cell Biology
Dentistry
Biography: 

Marc McKee is a full professor at McGill University in Montreal with a joint appointment in the Faculty of Dental Medicine and Oral Health Sciences, and in the Faculty of Medicine and Health Sciences (Department of Anatomy and Cell Biology).  He holds the Canada Research Chair in Biomineralization.  He received his B.Sc., M.Sc. and Ph.D. degrees from McGill University in cell biology, and completed a postdoctoral fellowship in the Department of Orthopedic Surgery at Harvard University and The Children's Hospital in Boston.  He then held academic appointments at the Forsyth Institute in Boston (1989), and at the University of Montreal (1990), after which he moved to McGill University in 1998.

The McKee lab currently has openings for graduate students, and is seeking candidates with at least some degree of research experience in academia or industry.

Contact Information
Email address: 
marc.mckee [at] mcgill.ca
Degree(s): 

Ph.D.

Position: 
Professor
Awards, honours, and fellowships: 
  • 2019  Adele L. Boskey AwardEsteemed Award from the American Society of Bone and Mineral Research
  • 2018  CP Leblond Award, Quebec provincial health research funding agency (FRQ-S) Network for Oral and Bone Health Research
  • 2018  Canada Research Chair in Biomineralization (Tier 1)Government of Canada CRC Chair Program
  • 2008  Faculty of Medicine Honour List for Educational ExcellenceMcGill University
  • 2006  James McGill ProfessorMcGill University Internal Chair Program
  • 2005  Faculty of Dentistry Howard S. Katz Award for Excellence in TeachingMcGill University
  • 2003  Basic Research in Biological Mineralization AwardDistinguished Scientist Award from the International Association for Dental Research
  • 2001  William Dawson ScholarMcGill University Internal Chair Program
  • 1996  Young Investigator AwardDistinguished Scientist Award from the International Association for Dental Research
  • 1996  Quebec Science (popular magazine) "Top-Ten" Discoveries of the Year, Role of osteopontin in mineralized tissues
  • 1994  Quebec Science (popular magazine) "Top-Ten" Discoveries of the Year, Bioactive coating for titanium implants
Areas of interest: 

Mineralization/calcification, mineralized tissues, bones, teeth, otoconia, rare bone and tooth mineralization diseases, osteomalacia/odontomalacia, mouse models of disease, hypophosphatasia, X-linked hypophosphatemia, electron and X-ray microscopy and tomography, osteopontin, eggshell, synthetic crystal growth and dissolution systems, nanostructure of biominerals

Professional activities: 
Current research: 

Research in McKee's laboratory is primarily focused on mineralization (calcification) of extracellular matrices in bones and teeth, in mineralization pathologies, and in other biomineralizing systems such as inner-ear otoconia and eggshells.  In particular, in addition to characterizing mineralization patterns in various tissues, he is investigating the role of mineral-binding proteins, peptides, amino acids, and small molecules – most notably a protein called osteopontin – and the enzymes that modify these biomolecules to influence their mineralization-regulating activities.  His studies on pathologic mineralization include work on rare bone diseases where skeletal and dental mineralization is defective (osteomalacia / odontomalacia), and bones and teeth are soft and deform.  His work also includes investigating the actions of regulatory molecules where debilitating mineral deposition occurs in soft tissues such as in the kidney (urolithiasis, kidney stones), in blood vessels (vascular calcification), and in tendon and ligament insertions (entheses).

McKee and McGill University colleague Natalie Reznikov have developed the concept of the Stenciling Principle for extracellular matrix mineralization which describes that at very specific locations in extracellular matrices, enzymes precisely control the selective removal (stenciling) of inhibitory small molecules (pyrophosphate) and proteins (osteopontin) to regulate mineral crystal growth.  The underlying notion of this principle derives from the original pivotal paradigm for double-negative regulation discovered by Francois Jacob and Jacques Monod in the late 1950s.  The paradigm of "repressing a repressor" to induce an activation effect – originally explaining genetic regulation of enzyme expression in bacteria – continues until today and explains many processes in developmental biology, cancer biology, and even ecology.  For bone, the Stenciling Principle describes a double-negative "inhibiting an inhibitor" scenario for enzyme-substrate/inhibitor pairs that permits and regulates the growth of small mineral foci in the extracellular matrix to eventually become a tightly packed, 3D crossfibrillar (collagen) mineralization pattern at the microscale termed crossfibrillar mineral tessellation.  This structural feature of bone is important for imparting micromechanical robustness to bone tissue – without it (as in osteomalacia), bones easily bend and deform.  Pertaining to the Stenciling Principle, McKee specifically focuses on the enzyme-substrate/inhibitor relationship between tissue-nonspecific alkaline phosphatase (TNAP, TNSALP, ALPL) and pyrophosphate (PPi), and between phosphate-regulating endopeptidase homolog X-linked (PHEX) and osteopontin (OPN).  He also investigates what goes wrong with mineralization in the rare bone diseases hypophosphatasia (HPP) and X-linked hypophosphatemia (XLH) that have inactivating gene mutations in TNAP and PHEX, respectively.

In parallel to his calcium-phosphate mineralization work, McKee has a longstanding research program on calcium-carbonate mineralization (eggshells, otoconia, and synthetic helical/chiral crystal suprastructures).  In past work, he examined extensively extracellular matrix organization and composition at cell-matrix and matrix-matrix interfaces (including at implantable biomaterial interfaces), and the tooth enamel maturation stage of amelogenesis.

Research methods

To study mineralization processes and mineralized tissue hierarchical structure at the nano- and microscale, a variety of morphological, biochemical, immunochemical, cell biological and molecular techniques are used which include among others: electron microscopy and electron tomography, focused-ion beam milling (FIB-SEM serial-surface-view with 3D reconstruction and deep learning approaches), atomic force microscopy, micro-computed tomography and other X-ray analytical approaches, optical microscopies, immunocytochemistry, in vivo experimentation using normal and transgenic mice, in vitro cell culture and crystal growth systems, standard biochemical and chemical assays, and computational simulations.

Research group/network affiliations

McKee is a member of the following research groups/networks: National Network for Canadian Oral Health Research, Québec FRQS Centre de Recherche en Biologie Structurale, Québec FRQS Réseau de Recherche en Santé Buccodentaire et Osseuse, McGill Centre for Bone and Periodontal Research, McGill Institute for Advanced Materials, McGill Sustainability Systems Initiative, and the McGill Regenerative Medicine Network.

Research areas: 

Mineralized Tissues and Extracellular Matrix Biology

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