COM4S_M.TTF

Research Focus

The research focus of the Davis laboratory is directed at understanding how thyroid hormone works on a molecular level and what cellular effects result from these actions. Dr. Davis and the Signal Transduction Laboratory team have found that a significant role of this hormone is to enhance the action of cytokines and growth factors. For example, thyroid hormone enhances the antiviral and immunomodulatory effects of interferon-γ and of epidermal growth factor (EGF). A collaboration with Dr. Shaker Mousa (Albany College of Pharmacy) has disclosed that thyroid hormone is pro-angiogenic, acting via a mechanism that is mitogen-activated protein kinase (MAPK/ERK1/2)- and fibroblast growth factor (FGF2)-dependent.

Thyroid hormone is well known to exert its action by means of a protein receptor located in cell nuclei. The Davis laboratory has determined that thyroid hormone also acts by means of a different receptor located at the plasma membrane of cells. When this receptor is activated, a cascade of changes in protein mediators takes place, culminating in a signal which can modify the activity of nuclear transactivator proteins, such as STAT proteins, p53 and members of the superfamily of nuclear hormone receptors. The laboratory has recently identified the plasma membrane receptor for thyroid hormone.

The laboratory also studies the mechanisms and cellular consequences of thyroid hormone-directed post-translational modifications (phosphorylation, acetylation) of nuclear hormone receptors and the hormone-directed compositional changes of enhanceosomes.

Selected Publications

• Lin, H-Y, Davis, FB, Gordinier, JK, Martino, LJ, and Davis, PJ. Thyroid hormone induces activation of mitogen-activated protein kinase in cultured cells. Amer J Physiol 276:C1014-C1024, 1999.
• Davis, PJ, Shih, A, Lin, H-Y, Martino, LJ and Davis, FB. Thyroxine promotes association of mitogen-activated protein kinase and nuclear thyroid hormone receptor (TR) and causes serine phosphorylation of TR. J Biol Chem 275:38032-38039, 2000.
• Shih, A, Lin, H-Y, Davis, FB, and Davis, PJ. Thyroid hormone promotes serine phosphorylation of p53 by mitogen-activated protein kinase. Biochemistry 40:2870-2878, 2001.
• Shih, A, Davis, FB, Lin, H-Y, and Davis, PJ. Resveratrol induces apoptosis in thyroid cancer cell lines via a MAPK- and p53-dependent mechanism. J Clin Endocrinol Metab 87:1223-1232, 2002.
• Lin, H-Y, Zhang, S, West, BL, Tang, H-Y, Passaretti, T, Davis, FB and Davis, PJ. Identification of the putative MAP kinase docking site in the thyroid hormone receptor-β1 DNA-binding domain: functional consequences of mutations at the docking site. Biochemistry 42:7571-7579, 2003.