These projects use a systems biology approach (using genomic, proteomic, and bioinformatic methods) to gain a greater insight into how metabolic function changes during life-span. This will involve conducting multiple tissue analyses on organs that are known to play a role in controlling metabolic function, such as: hypothalamus, pituitary gland, tongue, gut, pancreas, liver, adipose tissue, muscle, and gonads. Once we gain a greater insight into alterations in the metabolic/energy homeostasis super-axis during the aging process, we can then elucidate which pharmacological endocrine axes targets could be best used to enhance metabolic health. Pluripotent therapeutics that are targeted towards multiple aspects of the super-axis are likely to have much greater efficacy than those that target just one aspect in isolation.
We aim to elucidate and characterize - at a systemic level - endocrine regulation and feedback during the aging process, with special attention to euglycemic control axes and how these major energy axes may act as a master integrator for additional endocrine axes such as the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes. Therefore, multiple dietary, digestive and reproductive axes can be integrated at the humoral level to form a higher order super-axis. Many of the hormones that create the complex feedback loops in this super-axis provide a multi-level connection between cognitive appreciation of food supply, energy sensation/perception and eventual energy metabolism. Using animal models of aging or metabolic pathophysiology (e.g. type 2 diabetes, metabolic syndrome, Alzheimers disease) we will use various genomic, proteomic, bioinformatic and behavioral approaches to model and predict complex endocrine feedback loops and determine which pharmacological endocrine axes targets could be best used to enhance metabolic health and improve health-span during the aging process.
|Park, Sung-Soo; Wu, Wells W; Zhou, Yu et al. (2012) Effective correction of experimental errors in quantitative proteomics using stable isotope labeling by amino acids in cell culture (SILAC). J Proteomics 75:3720-32|
|Martin, Bronwen; Chadwick, Wayne; Cong, Wei-na et al. (2012) Euglycemic agent-mediated hypothalamic transcriptomic manipulation in the N171-82Q model of Huntington disease is related to their physiological efficacy. J Biol Chem 287:31766-82|
|Rothman, Sarah M; Herdener, Nathan; Camandola, Simonetta et al. (2012) 3xTgAD mice exhibit altered behavior and elevated AÎ² after chronic mild social stress. Neurobiol Aging 33:830.e1-12|
|Maudsley, S; Patel, S A; Park, S-S et al. (2012) Functional signaling biases in G protein-coupled receptors: Game Theory and receptor dynamics. Mini Rev Med Chem 12:831-40|
|Siddiqui, Sana; Fang, Meng; Ni, Bin et al. (2012) Central role of the EGF receptor in neurometabolic aging. Int J Endocrinol 2012:739428|
|Chadwick, Wayne; Mitchell, Nicholas; Martin, Bronwen et al. (2012) Therapeutic targeting of the endoplasmic reticulum in Alzheimer's disease. Curr Alzheimer Res 9:110-9|
|Driscoll, Ira; Martin, Bronwen; An, Yang et al. (2012) Plasma BDNF is associated with age-related white matter atrophy but not with cognitive function in older, non-demented adults. PLoS One 7:e35217|
|Wu, Wells W; Wang, Guanghui; Insel, Paul A et al. (2012) Discovery- and target-based protein quantification using iTRAQ and pulsed Q collision induced dissociation (PQD). J Proteomics 75:2480-7|
|Wu, Wells W; Shen, Rong-Fong; Park, Sung-Soo et al. (2012) Precursor ion exclusion for enhanced identification of plasma biomarkers. Proteomics Clin Appl 6:304-8|
|Chadwick, Wayne; Martin, Bronwen; Chapter, Megan C et al. (2012) GIT2 acts as a potential keystone protein in functional hypothalamic networks associated with age-related phenotypic changes in rats. PLoS One 7:e36975|
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