- Biological Sciences, Oxford University, 2019
- Postdoctoral Fellow
- Pathology, University of Michigan, 2016
- Postdoctoral Fellow
- Integrative Biology and Physiology, University of California Los Angeles, 2013
- Molecular and Computational Biology, University of Southern California, 2012
Areas of Interest
The Pickering lab is interested in biological questions about the aging process with the goal of development of treatments to allow people to stay healthy and active for longer. Our lab utilizes a number of model systems to answer these questions including fruit flies, mice and cell lines from long and short-lived animal species. Our particular focus is the role of proteostasis in aging and neurodegenerative diseases. We have demonstrated a modulatory role for the proteasome system in brain aging and Alzheimer’s disease. We have also shown tradeoff between protein synthesis and aging.
The proteasome in aging and Alzheimer’s disease
We are interested in the role of the proteasome system in aging and age-related diseases. We have found the proteasome system to be elevated in species that are under selection to be longer lived, a process that appears primarily driven by increases in the Immunoproteasome. In addition, we have reported neuronal-specific but not-ubiquitous proteasome augmentation to extend lifespan and slow age-related cognitive declines. Further, we have demonstrated proteasome augmentation to delay AD-like pathologies and developed a set of novel proteasome agonists.
Early life protein translation in aging and lifespan
We are interested in modulation of protein translation in lifespan. We have found protein translation to be elevated in early-life with a decline in protein translation rates across lifespan. We discovered that this represented an active repression of protein translation rates in later life to prevent or reduce later life proteostasis collapse. We demonstrated repression of protein translation in early life to significantly extend organismal lifespan though at the cost of early life reproduction. This is produced through a process involving juvenile hormone, modulation of accumulation of large lipid transfer proteins, regulation of germline stem cell proliferation and stress response pathways.
The mitochondrial thioredoxin system a metabolic and aging regulator
We are interested in the thioredoxin pathway. We became interested in this pathway after finding it to be enriched in species which are under selection to be long-lived. We specifically found elevations in the mitochondrial thioredoxin system in long lived species of rodent primates and birds. We went on to show that This system was elevated in several slow aging mouse models and that augmentation of the enzyme in the fruit fly Drosophila melanogaster could extend lifespan and improve activity at older ages. Furthermore, we have reported a role for the mitochondrial thioredoxin system as a novel metabolic regulator and to protect against metabolic disease.
- Kim HS, Parker DJ, Hardiman M, Munkácsy E, Rogers AN, Bai Y, Austad SN, Mobley JA, Pickering AM*. (2023). Nat Commun. Aug 18;14(1):5021. doi: 10.1038/s41467-023-40618-x. PMID: 37596266; PMCID: PMC10439225. (*corresponding Author). Impact factor 17.7
- Davidson K, Pickering AM*. (2023). The proteasome: A key modulator of nervous system function, brain aging, and neurodegenerative disease. Front Cell Dev Biol. Apr 13;11:1124907. doi: 10.3389/fcell.2023.1124907. (*Corresponding author) Impact factor 6.7.
- Kim HS, Pickering AM*. (2023). Protein translation paradox: Implications in translational regulation of aging. Front Cell Dev Biol. Jan 13;11:1129281. doi: 10.3389/fcell.2023.1129281. PMID: 36711035; PMCID: PMC9880214. (*Corresponding author) Impact factor 6.7.
- Chocron ES, Munkácsy E, Kim HS, Karpowicz P, Jiang N, Van Skike CE, DeRosa N, Banh AQ, Palavicini JP, Wityk P, Kalinowski L, Galvan V, Osmulski PA, Jankowska E, Gaczynska M, Pickering AM*. (2022). Genetic and pharmacologic proteasome augmentation ameliorates Alzheimer’s-like pathology in mouse and fly APP overexpression models. Sci Adv. Jun 10;8(23):eabk2252. doi: 10.1126/sciadv.abk2252. Epub 2022 Jun 8. PMID: 35675410; PMCID: PMC9177073. (*corresponding Author) Impact factor 14.1
- Kim HS, Son J, Lee D, Wang D, Munkácsy E, Tsai J, Jeong S, Kittrell P, Tobon A, Jackson CE, and Pickering AM*.(2022). Gut- and Oral-Dysbiosis Differentially Impact Spinal- and Bulbar-Onset ALS, Predicting ALS Severity and Potentially Determining the Location of Disease Onset. (*corresponding Author). BMC Neurology Impact factor 2.3.
- Chocron ES, Mdaki K, Jiang N, Cropper J, Pickering AM*.(2022). Mitochondrial Thioredoxin Reductase 2 enhances metabolic function and protects against metabolic disease through enhanced tricarboxylic acid cycle function. Communications Biology (*corresponding Author) Impact factor 6.3
- Munkacsy E, Pickering A.M*. Chapter 9, Model organisms (invertebrates). Handbook of Biology of Aging 9th
- Zhu Z, Achreja A, Meurs N, Animasahun O, Owen S, Mittal A, Parikh P, Lo T, Franco-Barraza J, Shi J, Gunchick V, Sherman MH, Cukierman E, Pickering AM, Maitra A, Sahai V, Morgan MA, Nagrath S, Lawrence TS, Nagrath D. (2020). Tumor-Reprogrammed Stromal BCAT1 Fuels Branched Chain Ketoacid 1 Dependency in Stromal-Rich PDAC Tumors. Nat Metab Impact factor 19.95
- Osmulski P, Karpowic P, Jankowska E, Bohmann J, Pickering AM, Gaczyńska M. New Peptide-Based Pharmacophore Activates 20S Proteasome. (2020). Molecules 25(6), 1439. Impact factor 4.9.
- Munkácsy E , Chocron ES Quintanilla L , Gendron C, Pletcher SD, Pickering AM*. (2019). Neuronal-specific Proteasome augmentation via Prosβ5 overexpression extends lifespan and reduces age-related cognitive decline. Aging Cell, Oct;18(5):e13005. doi: 10.1111/acel.13005. PMCID: PMC6718538. (*corresponding Author) Impact factor 11.0.
- Chocron ES, Munkácsy E, Pickering AM*. (2019). Cause or casualty: The role of mitochondrial DNA in aging and age-associated disease. Biochimica et biophysica acta. Molecular basis of disease. 1865(2):285-297. (*corresponding Author) Impact factor 6.6.
- Giżyńska M, Witkowska JP, Karpowicz P, Rostankowski R, Chocron ES, Pickering AM, Osmulski PA, Gaczynska ME, Jankowska E.J. (2018). Proline- and arginine-rich peptides as flexible allosteric modulators of human proteasome activity. Med Chem. Nov 19. doi: 10.1021/acs.jmedchem.8b01025 Impact factor 8.0.
- Handbook of Immunosenescence: Basic Understanding and Clinical Applications, 2nd 2017 DOI 10.1007/978-3-319-64597-1_111-1
- Pickering, AM., Lehr, M. & Miller, R. A. (2015). Mouse and primate lifespan is correlated with immunoproteasome expression. J Clin Invest. May 1;125(5):2059-68. Impact factor 19.46
- Pickering AM, Miller RA. The immunoproteasome system in aging, lifespan and age associated disease.
- Pickering AM*, Lehr M, Gendron CM, Pletcher SD, Miller RA. (2017). Mitochondrial thioredoxin reductase 2 is elevated in long-lived primate as well as rodent species and extends fly mean lifespan. Aging Cell. May 5. (*corresponding author) Impact factor 11.0
- 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, doi:10.1093/gerona/glu115. ‘J Gerontol A Biol Sci Med Sci Editors Choice’ Impact factor 6.1
- 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. Impact factor 7.4,
- 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. Impact factor 3.3
- Pickering A M, Davies K J A. (2012). Degradation of damaged proteins: the main function of the 20S proteasome. Prog Mol Biol Transl Sci. 109, pp. 227-48 Impact factor 3.6
- 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. 15;523(2), pp.181-90. Impact factor 4.0
- 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. Impact factor 5.5
- Pickering A M, Davies K J A. (2012). A simple fluorescence labeling method for studies of protein oxidation, protein modification, and proteolysis. Free Radic Biol Med. 52, pp. 239-46 Impact factor 7.4
- 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. 51 (7), pp. 1355-64. Impact factor 7.4
- 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. 15;432(3), pp. 585-94. Impact factor 4.1, ‘Most cited paper Biochem J, 2012’
- Nuzhdin, S. V., Brisson, J. A., Pickering, A. M., Wayne, M. L., Harshman, L. G., McIntyre, L. M. (2009). Natural genetic variation in transcriptome reflects network structure inferred with major effect mutations: insulin/TOR and associated phenotypes in Drosophila melanogaster. BMC Genomics. Vol. 10, pp. 124. Impact factor 4.6