EDUCATIONB.S. University of Kentucky, 1996
Ph.D. University of Kentucky, 1999
Molecular and Cellular Biology
RESEARCH INTERESTSBelow are some of the funded projects in Dr Keller’s laboratory which are focused on aging, oxidative stress, proteasome, and Alzheimer’s disease research. In addition to these projects, Dr Keller is working on 2 new major research efforts. First, Dr Keller is working on understanding the ability of a high fat diet to modulate brain function and brain pathology during aging. These efforts are a part of a multi-group effort at the PBRC and will result in the submission of a Program Project Grant proposal in early 2009. Secondly, Dr Keller has worked with others at PBRC to establish the Institute for Dementia Research & Prevention. This institute will include a longitudinal study of aging and dementia in individuals in Louisiana aged 60 and over, as well as include a platform for the identification of therapeutics for the prevention of dementia. Those interested in learning more on any of these research efforts, or wanting to participate in these research efforts, are encouraged to contact the IDRP at (225) 763-2973 or firstname.lastname@example.org Dr Keller for more details.
NIH/NIA 2PO1 AG005119 (Keller-Principal Investigator)
“The RAGE receptor and beta amyloid induced oxidative stress toxicity”
This project of the PPG examines the mechanism by which RAGE signaling contributes to A-beta induced toxicity and oxidative stress.
NIH/NIA 1RO1 AG025771 (Keller-Principal Investigator)
“Dietary restriction, aging and the proteasome”
This project quantified the changes in proteasome function in non-CNS tissues (immune, skeletal, hepatic, cardiovascular systems) that occur in response to aging and dietary restriction. Additionally, this grant will examine the effects of proteasome inhibition on non-CNS cells, and determine which features of aging are mediated by proteasome inhibition. These studies also explore the relationship between protein synthesis and protein degradation in non-CNS systems.
NIH/NIA 1RO1 AG029885 (Keller-Principal Investigator)
“Dietary restriction and proteasome mediated protein degradation in the CNS”.
This project quantified the changes in proteasome function in the CNS that occurs in response to aging and dietary restriction. Additionally, this grant will examine the effects of proteasome inhibition on CNS cells, and determine which features of aging are mediated by proteasome inhibition in the CNS. These studies also explore the relationship between the proteasome and oxidized protein regulation in the CNS.
Alzheimer’s Association Investigator Initiated Research Grant (Keller-Principal Investigator)
“HDAC inhibitors in in vitro and in vivo models of beta amyloid toxicity”
The goal of this proposal is to elucidate the therapeutic potential of histone deacytlase (HDAC) inhibitors in experimental model of beta amyloid toxicity. HDACs are commonly utilized in the treatment of some cancers and may provide benefit towards beta amyloid toxicity. These studies are intended to elucidate the ability of these compounds to be therapeutic in AD.
SELECTED PUBLICATIONSLi F, Zhang L, Craddock J, Bruce-Keller AJ, Dasuri K, Nguyen A, Keller JN.(2008) Aging and dietary restriction effects on ubiquitination, sumoylation, and the proteasome in theheart. Mech Ageing Dev. Sep;129(9):515-21.
Nelson PT, Smith CD, Abner EA, Schmitt FA, Scheff SW, Davis GJ, Keller JN, Jicha GA, David D, Wang WX, Hartman A, Katz DG, Markesbery WR. (2008) Human cerebral neuropathology of Type 2 diabetes mellitus. Biochim Biophys Acta. (In press)
Zhang L, Bruce-Keller AJ, Dasuri K, Nguyen A, Liu Y, Keller JN. (2008) Diet-Induced Metabolic Disturbances as modulators of brain homeostasis. Biochim Biophys Acta, (In press)
Ding Q, Cecarini V, Keller JN (2007) Interplay between protein synthesis and degradation in the CNS: physiological and pathological implications. Trends Neurosci. 30, 31-36.
Murphy MP, Beckett TL, Ding Q, Patel E, Markesbery WR, St Clair DK, LeVine H, Keller JN (2007) Abeta solubility and deposition during AD progression and in APP x PS1 knock-in mice. Neurobiol Dis. 27(3):301-11.
Zhang L, Li F, Dimayuga E, Craddock J, Keller JN. (2007) Effects of aging and dietary restriction on ubiquitination, sumoylation, and the proteasome in the spleen. FEBS Lett. 581(28):5543-7.
Ding Q, Dimayuga E, Markesbery WR, Keller JN (2006) Proteasome inhibition induces reversible impairments in protein synthesis. FASEB J 20, 1055-1063.
Keller JN, Schmidt FA, Ding Q, Chen Q, Scheff SW, Butterfield DA, Markesbery WR (2005) Increased oxidative stress in mild cognitive impairment. Neurology 64, 1152-1156.
Chen Q, Li F, Thorpe J, Dohmen RJ, Keller JN (2005) Extension of lifespan and decreasedoxidative stress in yeast expressing UMP1: central role for the proteasome? Free Radical Biol Med 40, 120-126.
Ding Q, Li F, Chen Q, Markesbery WR, Keller JN (2005) Ribosome dysfunction is an early event in AD. J Neurosci 25, 9171-9175. ^ top