[1] Levine's research has focused on identifying the molecular mechanisms underlying inherited disorders of mineral metabolism and the embryological development of the parathyroid glands.
His approach has been to apply molecular and genetic tools to analyze the basis of altered hormone action, particularly in G protein-coupled signal transduction systems that affect growth and development.
[7] In his early work, Levine focused on pseudohypoparathyroidism and Albright's hereditary osteodystrophy (AHO), an autosomal dominant disorder characterized by physical traits such as short stature, brachydactyly, and subcutaneous ossifications.
His work led to the discovery that pseudohypoparathyroidism type 1A is caused by defects in the maternal allele of the imprinted GNAS gene that lead to reduced expression or function of Gsα protein.
Moreover, he identified gain-of-function variants in CYP3A4, which encodes an enzyme that can inactivate many steroid hormones and drugs, as the basis for an unusual form of vitamin D dependent rickets.
[10] Levine and his associates showed that pathogenic variants in the ABCC6 gene, the cause of pseudoxanthoma elasticum, are also the basis for type 2 form of Generalized Arterial Calcification of Infancy (GACI).
It served as a compendium that linked the basic science of parathyroid hormone with major clinical disorders, offering practical information for managing these conditions.
[3] The Third Edition of The Parathyroids: Basic and Clinical Concepts covered significant updates in the field including on noninvasive imaging, fracture healing, secondary conditions like chronic kidney disease, and vitamin D metabolism.