Steven V John

Multi-omic analysis reveals nitric oxide dependent remodeling in classically activated macrophages and identifies negative regulation mediated by AKR1A1

Nicholas L Arp, Uzziah S. Urquiza, Marcel Morgenstern, Jonathan H Schrope et autres

Nitric oxide (NO•) is an important regulatory molecule in many biological processes, including immune response. During response to classical activation stimuli lipopolysaccharide (LPS) and interferon-γ (IFNγ), macrophages generate NO• via inducible nitric oxide synthase (iNOS). To comprehensively characterize the effects of NO•, …

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Discovery of metabolites produced by reactions between central carbon metabolites and cysteine that mark inflammatory macrophages

Nicholas L. Arp, J. Deng, Jorgo Lika, Gretchen L. Seim et autres

Abstract Identifying metabolites and metabolic reactions specific to a cellular state, such as inflammatory state in immune cells, is of great interest, as it can provide important biomarkers and point to compounds and reactions of specific biological functions. However, many cell state-specific …

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The pyruvate branch point controls lymphoid cancer cell dissemination

Hamidullah Khan, Steven V John, Sushmita Roy, Muhammad Farhan et autres

SUMMARY Cancer cell dissemination critically determines clinical prognosis, yet metabolic dependencies and corresponding therapeutic targets during spread of lymphoid malignancies remain poorly understood. Here we show that the pyruvate branch point operates as a metabolic checkpoint for lymphoid cancer cell migration and …

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Multi-omic analysis reveals nitric oxide dependent remodeling in classically activated macrophages and identifies negative regulation mediated by AKR1A1

Nicholas L Arp, Uzziah S. Urquiza, Marcel Morgenstern, Jonathan H Schrope et autres

ABSTRACT Nitric oxide (NO•) is an important signaling molecule in many biological processes, including immune response. During response to classical activation stimuli lipopolysaccharide (LPS) and interferon-γ (IFNγ), macrophages generate NO• via inducible nitric oxide synthase (iNOS). To comprehensively define the effects of …

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Classically activated macrophages undergo functionally significant nucleotide metabolism remodelling driven by nitric oxide

Steven V John, Gretchen L. Seim, Billy J Erazo-Flores, James A. Votava et autres

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Abstract 2071 Heme biosynthesis facilitates branched chain amino acid catabolic flux and controls Ucp1 expression in brown adipose tissue through histone propionylation

Dylan J. Duerre, Julia Hansen, Steven V John, Annie Jen et autres

Climate change, driven by increasing greenhouse gas emissions-particularly carbon dioxide (CO 2 )-remains a critical global challenge.The primary source of these emissions is the burning of fossil fuels for electricity, transportation, and heating.While efforts to reduce emissions are ongoing, a promising approach …

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Abstract 2822 Elucidating the role of HPRT in regulation of immune response in macrophages

Uzziah S. Urquiza, Steven V John, Jing Fan

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Abstract 2423 Feedback regulation of NO production on arginine metabolism in macrophages

Nicholas L. Arp, Uzziah S. Urquiza, Steven V John, Jing Fan

Macrophages are essential innate immune cells that reprogram arginine metabolism to support immune responses. Upon stimulation by bacterial components (e.g., lipopolysaccharide, LPS) and cytokines (e.g., interferon-gamma, IFNγ), macrophages upregulate nitric oxide synthase 2 (Nos2) to produce inducible nitric oxide synthase (iNOS), which …

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Haem biosynthesis regulates BCAA catabolism and thermogenesis in brown adipose tissue

Dylan J. Duerre, Julia K. Hansen, Steven V John, Annie Jen et autres

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Mining cholesterol genes from thousands of mouse livers identifies aldolase C as a regulator of cholesterol biosynthesis

James A. Votava, Steven V John, Zhonggang Li, Shuyang Chen et autres

The availability of genome-wide transcriptomic and proteomic datasets is ever-increasing and often not used beyond initial publication. Here, we applied module-based coexpression network analysis to a comprehensive catalog of 35 mouse genome-wide liver expression datasets (encompassing more than 3800 mice) with the …

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Macrophages undergo functionally significant reprograming of nucleotide metabolism upon classical activation

Steven V John, Gretchen L. Seim, Billy J Erazo-Flores, John Steill et autres

Abstract During an immune response, macrophages systematically rewire their metabolism in specific ways to support their diversve functions. However, current knowledge of macrophage metabolism is largely concentrated on central carbon metabolism. Using multi-omics analysis, we identified nucleotide metabolism as one of the …

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Heme biosynthesis regulates BCAA catabolism and thermogenesis in brown adipose tissue

Dylan J. Duerre, Julia K. Hansen, Steven V John, Annie Jen et autres

ABSTRACT With age, people tend to accumulate body fat and reduce energy expenditure 1 . Brown (BAT) and beige adipose tissue dissipate heat and increase energy expenditure via the activity of the uncoupling protein UCP1 and other thermogenic futile cycles 2,3 . …

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