Professor of Molecular Biology
Contact
jstock@princeton.edu609-258-6111
609-258-7844
Thomas Laboratory, 253
Stock Lab
Faculty Assistant
Minda AlenaEducation
B.A., Biophysics, Johns Hopkins UniversityPh.D., Biochemistry, Johns Hopkins University
Research Area
Biochemistry, Biophysics & Structural BiologyResearch Focus
Membrane receptors and signal transductionResearch
Selected Publications
Biography
We are primarily concerned with the development of novel pharmaceuticals to regulate signal transduction pathways that underlie chronic diseases associated with inflammation and aging. The activities of approximately a third of the proteins in vertebrate cells are regulated by reversible phosphorylation at serine and threonine resides. There are almost a thousand different protein kinases, each of which catalyzes the transfer of phosphoryl groups from ATP to a specific set of protein substrates in response to a regulatory input. In contrast, there are just a few phosphoprotein phosphatases to catalyze the removal of these groups. Our research over the past several years has focused on the molecular mechanisms that underlie the regulation of these phosphatases. Through these efforts we have identified potential pharmaceutical targets for the global regulation of phosphatase activity, developed screens for useful therapeutic agents, and characterized pharmaceutical leads that provide a basis for further medicinal chemistry exploration. Our current research is essentially translational, with two principal targets: skin and brain.
The skin project targets inflammatory diseases such as psoriasis, rosacea, atopic dermatitis, and acne as well as the general problem of skin aging. Our brain research is concerned with neurodegenerative diseases such as Parkinson’s and Alzheimer’s. Both projects focus on the regulation and pharmacuetical modulation of the most abundant phosphoprotein phosphatase, phosphoprotein phosphatase 2A (PP2A). Several years ago we discovered that PP2A activity is regulated by reversible carboxyl methylation. This modification is catalyzed by two PP2A-specific converter enzymes, a methyltransferase (PPMT) and a methylesterase (PME). Demethylation is associated with inflammation, apoptosis, and neurodegeneration. We have identified several different pharmaceutical chemotypes that bind to PP2A and inhibit its demethylation by PME. We have shown that one agent, a natural product found in coffee, is efficacious in animal models for neurodegeneration and skin inflammation.
Kikuchi Y, Sugano E, Yuki S, Tabata K, Endo Y, Takita Y, et al. SIG-1451, a Novel, Non-Steroidal Anti-Inflammatory Compound, Attenuates Light-Induced Photoreceptor Degeneration by Affecting the Inflammatory Process. Int J Mol Sci. 2022 ;23(15). PubMed
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Huber KL, Fernández JR, Webb C, Rouzard K, Healy J, Tamura M, et al.. AGSE: A Novel Grape Seed Extract Enriched for PP2A Activating Flavonoids That Combats Oxidative Stress and Promotes Skin Health. Molecules. 2021 ;26(21). PubMed
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Voronkov M, Ataiants J, Cocchiaro B, Stock JB, Lankenau SE. A vicious cycle of neuropathological, cognitive and behavioural sequelae of repeated opioid overdose. Int J Drug Policy. 2021 ;97:103362. PubMed
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Voronkov M, Cocchiaro B, Stock JB. Does a hypoxic injury from a non-fatal overdose lead to an Alzheimer Disease?. Neurochem Int. 2021 ;143:104936. PubMed
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Huber KL, Fernández JR, Webb C, Rouzard K, Healy J, Tamura M, et al.. HYVIA?: A novel, topical chia seed extract that improves skin hydration. J Cosmet Dermatol. 2020 ;19(9):2386-2393. PubMed
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Yan R, Zhang J, Park H-J, Park ES, Oh S, Zheng H, et al. Synergistic neuroprotection by coffee components eicosanoyl-5-hydroxytryptamide and caffeine in models of Parkinson's disease and DLB. Proc Natl Acad Sci U S A. 2018 ;115(51):E12053-E12062. PubMed
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Fernández JR, Webb C, Rouzard K, Healy J, Tamura M, Voronkov M, et al.. SIG1459: A novel phytyl-cysteine derived TLR2 modulator with in vitro and clinical anti-acne activity. Exp Dermatol. 2018 ;27(9):993-999. PubMed
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Park H-J, Lee K-W, Oh S, Yan R, Zhang J, Beach TG, et al. Protein Phosphatase 2A and Its Methylation Modulating Enzymes LCMT-1 and PME-1 Are Dysregulated in Tauopathies of Progressive Supranuclear Palsy and Alzheimer Disease. J Neuropathol Exp Neurol. 2018 ;77(2):139-148. PubMed
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Fernández JR, Webb C, Rouzard K, Voronkov M, Huber KL, Stock JB, et al.. N-Acetylglutaminoyl-S-farnesyl-L-cysteine (SIG-1191): an anti-inflammatory molecule that increases the expression of the aquaglyceroporin, aquaporin-3, in human keratinocytes. Arch Dermatol Res. 2017 ;309(2):103-110. PubMed
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Asam K, Staniszewski A, Zhang H, Melideo SL, Mazzeo A, Voronkov M, et al. Eicosanoyl-5-hydroxytryptamide (EHT) prevents Alzheimer's disease-related cognitive and electrophysiological impairments in mice exposed to elevated concentrations of oligomeric beta-amyloid. PLoS One. 2017 ;12(12):e0189413. PubMed
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Fernández JR, Rouzard K, Voronkov M, Huber KL, Webb C, Stock JB, et al.. In vitro and clinical evaluation of SIG1273: a cosmetic functional ingredient with a broad spectrum of anti-aging and antioxidant activities. J Cosmet Dermatol. 2016 ;15(2):150-7. PubMed
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Park H-J, Lee K-W, Park ES, Oh S, Yan R, Zhang J, et al. Dysregulation of protein phosphatase 2A in parkinson disease and dementia with lewy bodies. Ann Clin Transl Neurol. 2016 ;3(10):769-780. PubMed
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Fernandéz JR, Rouzard K, Voronkov M, Huber KL, Stock JB, Stock M, et al.. Anti-inflammatory and anti-bacterial properties of tetramethylhexadecenyl succinyl cysteine (TSC): a skin-protecting cosmetic functional ingredient. Int J Cosmet Sci. 2015 ;37(1):129-33. PubMed
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Basurto-Islas G, Blanchard J, Tung YChyn, Fernández JR, Voronkov M, Stock M, et al.. Therapeutic benefits of a component of coffee in a rat model of Alzheimer's disease. Neurobiol Aging. 2014 ;35(12):2701-2712. PubMed
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Stock JB, Zhang S. The biochemistry of memory. Curr Biol. 2013 ;23(17):R741-5. PubMed
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Xing Y, Li Z, Chen Y, Stock JB, Jeffrey PD, Shi Y. Structural mechanism of demethylation and inactivation of protein phosphatase 2A. Cell. 2008 ;133(1):154-63. PubMed
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Jeffry B. Stock is a leading expert in signal transduction and global cellular regulation with over 150 original scientific articles in this and related areas. He is best known for his seminal work on membrane receptor function and signal transduction in micro-organisms. As a graduate student at Johns Hopkins in the early 70s he played a key role in elucidating the chemiosmotic relationships and bioenergetics of active transport and membrane receptor function in bacteria.?? As a postdoctoral fellow at Berkeley and later as a Professor and independent investigator at Princeton, Dr. Stock has made numerous contributions toward understanding the molecular mechanism of sensory-motor regulation in prokaryotes. He was the first to elucidate the so-called two-component phosphorelay biochemistry that underlies sensory-motor regulation in specific, and serves generally to regulate bacterial responses to changing environmental conditions.
Although for most of his career Dr Stock’s research has focused on the basic biochemistry and molecular biology of cellular regulation; for the past decade he has been increasingly involved in translational research to apply the lessons derived from basic research to drug discovery and the development of useful therapeutics. Toward this end, Dr. Stock has founded several biotech startups including most recently the Signum Biosciences Group, for which he serves as Chairman. These efforts have lead to the development of topical anti-inflammatories for dermatological applications, as well as a novel systemic approach for the treatment of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Dr. Stock has received numerous honors. He is an elected fellow of the American Academy of Microbiology and the American Association for the Advancement of Science, and a winner of the Humboldt Prize. He serves on the Centers Review Committee for the National Institute of Drug Abuse.
The Biochemistry of Memory