My research has two major objectives: the first is directed toward
understanding receptor mechanisms involved in regulating tyrosine
hydroxylase (TH) gene expression, the rate limiting enzyme in the
synthesis of catecholamines. The latter substances are crucially
involved in various life-sustaining functions and are implicated in
diseases such as hypertension, depression and Parkinson’s disease. We
are examining the signal transduction mechanisms that mediate the
effects of selected neurotransmitter and neuromodulators on TH gene
expression in a cultured adrenal chromaffin cell line. Most recently, we
have focused on vasoactive intestinal peptide and pituitary adenylate
cyclase-activating polypeptide (PACAP) receptors and glucocorticoid
receptors. We have investigated both transcriptional and
post-transcriptional responses to PACAP and VIP and found that the PAC1
receptor distinguishes between the two agonists by stabilizing TH mRNA
in response to PACAP, but not VIP. We are investigating intracellular
signaling pathways in this response. We also recently identified the
glucocorticoid responsive element in the promoter region of the TH gene.
We are examining how second messenger pathways that are stimulated by
neuropeptide receptors modulate the transcriptional responses to
Hasty P, Livi CB, Dodds SG, Jones D, Strong R, Javors M, Fischer KE,
Sloane L, Murthy K, Hubbard G, Sun L, Hurez V, Curiel TJ, Sharp ZD. Rapa restores a normal life span in a FAP mouse model. Cancer Prev Res (Phila). 2014 Jan;7(1):169-78.
Miller RA, Harrison DE, Astle CM, Fernandez E, Flurkey K, Han M, Javors
MA, Li X, Nadon NL, Nelson JF, Pletcher S, Salmon AB, Sharp ZD, Van
Roekel S, Winkleman L, Strong R. Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction. Aging Cell. 2013 Dec 17.
Harrison DE, Strong R, Allison DB, Ames BN, Astle CM, Atamna H,
Fernandez E, Flurkey K, Javors MA, Nadon NL, Nelson JF, Pletcher S,
Simpkins JW, Smith D, Wilkinson JE, Miller RA. Acarbose, 17-α-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males. Aging Cell. 2014 Apr;13(2):273-82.
Strong R, Miller RA, Astle CM, Baur JA, de Cabo R, Fernandez E, Guo W,
Javors M, Kirkland JL, Nelson JF, Sinclair DA, Teter B, Williams D,
Zaveri N, Nadon NL, Harrison DE. Evaluation
of resveratrol, green tea extract, curcumin, oxaloacetic acid, and
medium-chain triglyceride oil on life span of genetically heterogeneous
mice. J Gerontol A Biol Sci Med Sci. 2013 Jan;68(1):6-16.
Livi CB, Hardman RL, Christy BA, Dodds SG, Jones D, Williams C, Strong
R, Bokov A, Javors MA, Ikeno Y, Hubbard G, Hasty P, Sharp ZD. Rapamycin extends life span of Rb1+/- mice by inhibiting neuroendocrine tumors. Aging (Albany NY). 2013 Feb;5(2):100-10.