Full Text Journal Articles by
Author Alexander W Sorum


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Sulfated glycans engage the Ang-Tie pathway to regulate vascular development.

Matthew E Griffin, Alexander W Sorum, Gregory M Miller, William A Goddard, Linda C Hsieh-Wilson,

The angiopoietin (Ang)-Tie pathway is essential for the proper maturation and remodeling of the vasculature. Despite its importance in disease, the mechanisms that control signal transduction through this pathway are poorly understood. Here, we demonstrate that heparan sulfate glycosaminoglycans (HS GAGs) regulate Ang-Tie signaling through direct interactions with both Ang ... Read more >>

Nat Chem Biol (Nature chemical biology)
[2020, :]

Cited: 0 times

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Tau Internalization is Regulated by 6-O Sulfation on Heparan Sulfate Proteoglycans (HSPGs).

Jennifer N Rauch, John J Chen, Alexander W Sorum, Gregory M Miller, Tal Sharf, Stephanie K See, Linda C Hsieh-Wilson, Martin Kampmann, Kenneth S Kosik,

The misfolding and accumulation of tau protein into intracellular aggregates known as neurofibrillary tangles is a pathological hallmark of neurodegenerative diseases such as Alzheimer's disease. However, while tau propagation is a known marker for disease progression, exactly how tau propagates from one cell to another and what mechanisms govern this ... Read more >>

Sci Rep (Scientific reports)
[2018, 8(1):6382]

Cited: 25 times

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Defining Metabolic and Nonmetabolic Regulation of Histone Acetylation by NSAID Chemotypes.

Jonathan H Shrimp, Julie M Garlick, Tugsan Tezil, Alexander W Sorum, Andrew J Worth, Ian A Blair, Eric Verdin, Nathaniel W Snyder, Jordan L Meier,

Nonsteroidal anti-inflammatory drugs (NSAIDs) are well-known for their effects on inflammatory gene expression. Although NSAIDs are known to impact multiple cellular signaling mechanisms, a recent finding is that the NSAID salicylate can disrupt histone acetylation, in part through direct inhibition of the lysine acetyltransferase (KAT) p300/CBP. While salicylate is a ... Read more >>

Mol Pharm (Molecular pharmaceutics)
[2018, 15(3):729-736]

Cited: 1 time

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Salicylate, diflunisal and their metabolites inhibit CBP/p300 and exhibit anticancer activity.

Kotaro Shirakawa, Lan Wang, Na Man, Jasna Maksimoska, Alexander W Sorum, Hyung W Lim, Intelly S Lee, Tadahiro Shimazu, John C Newman, Sebastian Schröder, Melanie Ott, Ronen Marmorstein, Jordan Meier, Stephen Nimer, Eric Verdin,

Salicylate and acetylsalicylic acid are potent and widely used anti-inflammatory drugs. They are thought to exert their therapeutic effects through multiple mechanisms, including the inhibition of cyclo-oxygenases, modulation of NF-κB activity, and direct activation of AMPK. However, the full spectrum of their activities is incompletely understood. Here we show that ... Read more >>

Elife (eLife)
[2016, 5:]

Cited: 23 times

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Microfluidic Mobility Shift Profiling of Lysine Acetyltransferases Enables Screening and Mechanistic Analysis of Cellular Acetylation Inhibitors.

Alexander W Sorum, Jonathan H Shrimp, Allison M Roberts, David C Montgomery, Neil K Tiwari, Madhu Lal-Nag, Anton Simeonov, Ajit Jadhav, Jordan L Meier,

Lysine acetyltransferases (KATs) are critical regulators of signaling in many diseases, including cancer. A major challenge in establishing the targetable functions of KATs in disease is a lack of well-characterized, cell-active KAT inhibitors. To confront this challenge, here we report a microfluidic mobility shift platform for the discovery and characterization ... Read more >>

ACS Chem Biol (ACS chemical biology)
[2016, 11(3):734-741]

Cited: 8 times

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Characterizing the Covalent Targets of a Small Molecule Inhibitor of the Lysine Acetyltransferase P300.

Jonathan H Shrimp, Alexander W Sorum, Julie M Garlick, Laura Guasch, Marc C Nicklaus, Jordan L Meier,

C646 inhibits the lysine acetyltransferases (KATs) p300 and CBP and represents the most potent and selective small molecule KAT inhibitor identified to date. To gain insights into the cellular activity of this epigenetic probe, we applied chemoproteomics to identify covalent targets of the C646 chemotype. Modeling and synthetic derivatization was ... Read more >>

(ACS medicinal chemistry letters)
[2016, 7(2):151-155]

Cited: 21 times

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Metabolic Regulation of Histone Acetyltransferases by Endogenous Acyl-CoA Cofactors.

David C Montgomery, Alexander W Sorum, Laura Guasch, Marc C Nicklaus, Jordan L Meier,

The finding that chromatin modifications are sensitive to changes in cellular cofactor levels potentially links altered tumor cell metabolism and gene expression. However, the specific enzymes and metabolites that connect these two processes remain obscure. Characterizing these metabolic-epigenetic axes is critical to understanding how metabolism supports signaling in cancer, and ... Read more >>

Chem Biol (Chemistry & biology)
[2015, 22(8):1030-1039]

Cited: 21 times

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Defining the orphan functions of lysine acetyltransferases.

David C Montgomery, Alexander W Sorum, Jordan L Meier,

Long known for their role in histone acetylation, recent studies have demonstrated that lysine acetyltransferases also carry out distinct "orphan" functions. These activities impact a wide range of biological phenomena including metabolism, RNA modification, nuclear morphology, and mitochondrial function. Here, we review the discovery and characterization of orphan lysine acetyltransferase ... Read more >>

ACS Chem. Biol. (ACS chemical biology)
[2015, 10(1):85-94]

Cited: 14 times

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