William Michael Philbrick PhD

Senior Research Scientist in Medicine (Endocrinology); Director, Diabetes Endocrinology Research Center Molecular Core

Research Interests

Parathyroid hormone-related peptide (PTHrP)

Research Summary

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.

Selected Publications

  • Enhanced fasting glucose turnover in mice with disrupted action of TUG protein in skeletal muscle. Löffler MG, Birkenfeld AL, Philbrick KM, Belman JP, Habtemichael EN, Booth CJ, Castorena CM, Choi CS, Jornayvaz FR, Gassaway BM, Lee HY, Cartee GD, Philbrick W, Shulman GI, Samuel VT, Bogan JS. J Biol Chem. 2013 Jul 12;288(28):20135-50. doi: 10.1074/jbc.M113.458075. Epub 2013 Jun 6.
  • NLRP6 inflammasome orchestrates the colonic host-microbial interface by regulating goblet cell mucus secretion. Wlodarska M, Thaiss CA, Nowarski R, Henao-Mejia J, Zhang JP, Brown EM, Frankel G, Levy M, Katz MN, Philbrick WM, Elinav E, Finlay BB, Flavell RA. Cell. 2014 Feb 27;156(5):1045-59. doi: 10.1016/j.cell.2014.01.026.

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