Kelly T Dineley, Ph.D. Professor,
Department of Neurology
Director, Rodent In Vivo Assessment Core
Phone: (409) 747-7060
Fax: (409) 747-7050
Link to Own Website
02/98 Ph.D., Neuroscience, Baylor College of Medicine, Houston, TX
06/86 M.S., Cell Biology, University of the Pacific, Stockton, CA
06/83 B.A., Biology, University of the Pacific, Stockton, CA
- Alzheimer’s disease and Parkinson’s disease and related proteinopathies: amyloidopathies, tauopathies, synucleinopathies.
- Cocaine abuse and addiction.
- Animal models utilizing genetic and pharmacological manipulations.
- Omics and bioinformatics approaches for the identification and validation of novel mechanisms that underlie memory and cognitive deficits induced by aging, neurodegenerative disease, and drug abuse.
- Nicotinic acetylcholine receptors, nuclear receptors (PPAR), ERK MAPK, CREB, CBP, calcineurin, protein-protein interactions.
Beginning with seminal work establishing amyloid-β (Aβ)-nicotinic acetylcholine receptor (nAChR) interaction that laid the foundation for a series of publications elucidating the role of α7 nAChRs in early Alzheimer’s disease (AD) as well as mechanistic discoveries implicating calcineurin and peroxisome proliferator-activated receptor–γ (PPARγ) in early AD hippocampal dysfunction. Subsequent work has investigated temporal cortex circuit disruptions and translational interventions to normalize intrinsic properties, synaptic plasticity, and memory. Parallel activities have generated novel tools and technologies and broadly cited reviews that have helped guide the field of neurological disease including AD.
- Molecular and cellular mechanisms of hippocampal dysfunction in early Alzheimer’s disease
- Dineley KT, Westerman M, Bui D., Bell K, Hsiao Ashe K and Sweatt J.D. (2001) Beta-amyloid activates the mitogen-activated protein kinase cascade through hippocampal α7 nicotinic acetylcholine receptors: in vitro and in vivo mechanisms related to Alzheimer’s disease. J. Neurosci. 21:4125-4133. PMID: 11404397
- Dineley KT, Xia X, Bui D., Sweatt JD and Zheng H. (2002) Accelerated plaque accumulation, associative learning deficits and up-regulation of α7 nicotinic acetylcholine receptor protein in transgenic mice co-expressing mutant human presenilin 1 and amyloid precursor proteins. J. Biol. Chem. 277:22768-22780. PMID:11912199
- Hernandez CM, Kayed R, Zheng H, Sweatt JD and Dineley KT (2010) Loss of α7 nicotinic receptors enhances Aβ oligomer accumulation exacerbating early-stage cognitive decline and septo-hippocampal pathology in a mouse model for Alzheimer’s disease. J Neurosci. 30(7):2442–2453. PMID: 20164328
- Jahrling JB, Hernandez CM, Denner L, Dineley KT (2014) PPARγ recruitment to active ERK during memory consolidation is required for Alzheimer’s disease-related cognitive enhancement. J Neurosci. Mar 12;34(11):4054-63. doi: 10.1523/JNEUROSCI.4024-13.2014. PMID: 24623782
- Translational investigations into cognitive enhancers and disease-modifying interventions for neurodegenerative diseases
- Taglialatella G, Hogan D, Zhang W-R and Dineley KT (2009) Intermediate- and long-term recognition memory deficits in Tg2576 mice are reversed with acute calcineurin inhibition. Behav Brain Res. 200(1):95-9. PMID: 19162087
- Denner LA, Rodriguez-Rivera J, Haidacher SJ, Jahrling JB, Carmical JR, Hernandez CM, Zhao Y, Sadygov RG, Starkey JM, Spratt H, Luxon BA, Wood TG, Dineley KT (2012) Cognitive Enhancement with Rosiglitazone Links the Hippocampal PPARγ and ERK MAPK Signaling Pathways. J Neurosci 32(47):16725-35. PMID: 23175826
- Castillo-Carranza DL, Guerrero-Muñoz MJ, Sengupta U, Hernandez C, Barrett AD, Dineley KT, Kayed R. Tau immunotherapy modulates both pathological tau and upstream amyloid pathology in Alzheimer’s disease mouse model. (2015) Mar 25;35(12):4857-68. doi: 10.1523/JNEUROSCI.4989-14.2015. PMID: 25810517.
- Miller WR, Fox RG, Stutz SJ, Lane SD, Denner L, Cunningham KA, Dineley KT. PPARγ agonism attenuates cocaine cue reactivity. (2016) Neuropsychopharm. in revision.
- Circuit alterations resulting from neurological disease
- Pirttimaki T, Codadu NK, Awni A, Pratik P, Nagel D, Hill EJ, Dineley KT, Parri HR (2013) α7 nicotinic receptor-mediated astrocytic gliotransmitter release: Aβ effects in a preclinical Alzheimer’s mouse model. PLoS ONE November 28;8(11):e81828. doi: 10.1371/journal.pone.0081828. PMID: 24312364
- Nenov MN, Laezza F, Haidacher SJ, Zhao Y, Sadygov RG, Starkey JM, Spratt H, Luxon BA, Dineley KT, Denner L. (2013) Cognitive enhancing treatment with a PPARγ agonist normalizes dentate granule cell presynaptic function in Tg2576 APP mice. J Neurosci 34(3):1028-36. doi: 10.1523/JNEUROSCI.3413-13.2014 PMID:24431460
- Nenov MN, Tempia F, Denner L, Dineley KT, Laezza F (2014) Impaired firing properties of dentate granule neurons in an Alzheimer's disease animal model are rescued by PPARγ agonism. J Neurophys Dec 24:jn.00419.2014. doi: 10.1152/jn.00419.2014. PMID: 25540218
- Novel in vivo and in vitro tools
- *Neff S., *Dineley K.T., Char D., Quik M., and Patrick J. (1995) Production of polyclonal antisera that recognize and distinguish between the extracellular domains of neuronal nicotinic acetylcholine receptor subunits. J. Neurochem. 64:332-339. *equal authorship
- *Goldner F., *Dineley K.T., and Patrick J. (1997) Immunohistochemical localization of the nicotinic acetylcholine receptor subunit alpha6 to dopaminergic neurons in the substantia nigra and ventral tegmental area. NeuroReport 8:2739-2742. PMID: 9295110 *equal authorship
- Dineley K.T. and Patrick J. (2000) Molecular determinants of alpha7 nAChR surface expression. J. Biol. Chem. 275:13974-13985. PMID: 10788524
- Hernandez CM, Cortez I, Gu Z, Colón-Sáez JO, Lamb PW, Wakamiya M, Yakel JL, Dineley KT (2014) Research tool: valid
- Key review articles guiding neurological disease research
- Dineley KT. Aβ peptide and nicotinic acetylcholine receptor interaction: The two faces of health and disease. (2007) Frontiers in Bioscience: Nicotinic Acetylcholine Receptors in Adult and Developing Brain. 12: 5030-5038. PMID: 17569627
- Hernandez CM, Dineley KT (2012) α7 nicotinic acetylcholine receptors in Alzheimer’s disease: neuroprotective, neurotrophic, or both? Curr Drug Targets. 13(5):613-22. PMID: 22300028
- Dineley KT, Jahrling JB, Denner L (2014) Insulin Resistance in Alzheimer’s Disease. Neurobiol of Disease. 72PA:92-103 PMID:25237037
- Dineley KT, Pandya AA, Yakel JL (2014) Nicotinic ACh Receptors as Therapeutic Targets in CNS Disorders. Trends Pharmacol Sci. 2015 Feb;36(2):96-108. doi:10.1016/j.tips.2014.12.002. Epub 2015 Jan 29. PMID: 25639674
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