William Philbrick, PhD

Parathyroid hormone-related peptide (PTHrP) is a multifunctional protein which plays a role in the inhibition of programmed differentiation in a number of systems. To explore the role of this peptide in development, we have taken a targeted overexpression approach using transgenic mice. In the epidermis, PTHrP delays hair follicle initiation, while in the mammary gland and bone, it acts as a potent inhibitor of branching morphogenesis and endochondral ossification, respectively. Current projects include further characterization of these systems both in vivo and in vitro and investigation of the role of PTHrP in the development of the lung and the immune system.

When overproduced by tumors, PTHrP can enter the circulation and react with classical PTH receptors in bone and kidney resulting in hypercalcemia. We have found that PTHrP gene expression is regulated by methylation of critical sites in the promoter, by the levels of specific trans-acting factors, and finally by stabilization of the tumor suppressor, p53. We are presently engaged in characterizing the nature of the DNA-protein interactions involved in all three mechanisms.

Specialized Terms: Parathyroid hormone-related peptide (PTHrP)