​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 unwanted and 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). His group studies how tissues are hardened by the so-called Stenciling Principle of mineralization where, at very specific locations in extracellular matrices, enzymes precisely control the selective removal of inhibitory proteins, peptides and small molecules (pyrophosphate) to regulate mineral crystal growth. This principle describes the growth of small mineral foci in the extracellular matrix to form a tightly packed, 3D crossfibrillar (collagen) mineralization pattern at the microscale which in bone we has been termed crossfibrillar mineral tessellation.  He particularly focuses on the enzyme-inhibitor relationship between tissue-nonspecific alkaline phosphatase (TNAP, ALPL) and pyrophosphate (PPi), and between phosphate-regulating endopeptidase homolog X-linked (PHEX) and osteopontin (OPN), and he 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 other work, based on findings describing underlying mechanisms guiding mineralization, his group has recently shown how chiral amino acids can be used to produce synthetic, helical chiral suprastructures of calcium carbonate mineral.