The goal of my laboratory is to identify novel factors and pathways that regulate aging or age associated diseases. In this work we make use of two model systems. The first is a cross-species cell culture model. The second is genetic manipulation of the fruit fly Drosophila melanogaster
We make use of a cross-species model as there is extraordinary variation in lifespan amongst the animal kingdom. Some species will only live a few months or years while other species will live many decades. A few species can even live multiple centuries.
This variation in lifespan is the product of different evolutionary pressures in different species. For instance species with few predators, a long development time and few offspring are under greater pressure to evolve strategies to slow aging rates than species with many predators, many offspring and short development times.
My lab is interested in investigating factors that are enriched in species under selection for a longer lifespan. We consider this a powerful screening tool to identify factors which may be important regulators of aging. This approach has the advantage of enabling an evaluation of many factors relatively quickly without the time and cost constraints to lifespan analysis in transgenic animals.
A second area of research in my lab makes use of is the fruit fly Drosophila melanogaster. This animal has powerful genetic tools which allow us to directly test whether augmentation or depletion of the factors we found to be interesting in our cross species model can slow progression of aging or age associate diseases.
Pickering A M, Lehr M, Miller RA. Lifespan of mice and primates correlates with immunoproteasome expression. J Clin Invest. 2015 May;125(5):2059-68. doi: 10.1172/JCI80514. PMCID: PMC4463211
Pickering, A M., Lehr, M., Kohler, W. J., Han, M. L. & Miller, R. A. (2014) Fibroblasts From Longer-Lived Species of Primates, Rodents, Bats, Carnivores, and Birds Resist Protein Damage. J Gerontol A Biol Sci Med Sci, 2015 Jul;70(7):791-9. doi: 10.1093/gerona/glu115 PMCID: PMC4481684
Pickering A M, Staab T A, Tower J, Sieburth S, Davies K J A. (2013) A Conserved Role for the 20S Proteasome and Nrf2 Transcription Factor in Oxidative-Stress Adaptation in Mammals, C. elegans and D. melanogaster. J Exp Biol. Vol. 15;216(Pt 4), pp.543-53. PMCID: PMC3561776
Pickering A M, Vojtovicha L, Tower J, Davies K J A. (2013) Oxidative Stress Adaption with Acute, Chronic and Repeated Stress. Free Radic Biol Med. Vol. 55, pp. 109-18. PMCID: PMC3687790
Pickering A M, Linder RA, Zhang H, Forman H J, Davies K J A. (2012). Nrf2-dependent Induction of Proteasome and Pa28αβ Regulator Are Required for Adaptation to Oxidative Stress. J Biol Chem. Vol. 23;287(13), pp. 10021-31. PMCID: PMC3323025
Pickering A M, Davies K J A. (2012) Differential roles of proteasome and immunoproteasome regulators Pa28αβ, Pa28γ and Pa200 in the degradation of oxidized proteins. Arch Biochem Biophys. Vol. 15;523(2), pp.181-90. PMCID: PMC3384713
Pickering A M, Davies K J A.(2012) Degradation of damaged proteins: the main function of the 20S proteasome. Prog Mol Biol Transl Sci. Vol. 109, pp. 227-48 PMCID: PMC3710712
Grune T, Catalgol B, Licht A, Ermak G, Pickering, A M, Ngo J K, Davies K J A. (2011). HSP70 mediates dissociation and reassociation of the 26S proteasome during adaptation to oxidative stress. Free Radic Biol Med. Vol. 51 (7), pp. 1355-64. PMCID: PMC3172204
Pickering, A M, Koop A L, Teoh C Y, Ermak G, Grune T, Davies K J A. (2010). The immunoproteasome, the 20S proteasome, and the PA28aß proteasome regulator are oxidative stress-adaptive proteolytic complexes. Biochem J. Vol. 15;432(3), pp. 585-94. PMCID: PMC3133595