Full Text Journal Articles by
Author Heather Smallwood

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Influenza A virus directly modulates mouse eosinophil responses.

Kim S LeMessurier, Robert Rooney, Hazem E Ghoneim, Baoming Liu, Kui Li, Heather S Smallwood, Amali E Samarasinghe,

Allergic asthma and influenza are common respiratory diseases with a high probability of co-occurrence. During the 2009 influenza pandemic, hospitalized patients with influenza experienced lower morbidity if asthma was an underlying condition. We have previously demonstrated that acute allergic asthma protects mice from severe influenza and have implicated eosinophils in ... Read more >>

J. Leukoc. Biol. (Journal of leukocyte biology)
[2020, :]

Cited: 0 times

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Discovery and Predictive Modeling of Urine Microbiome, Metabolite and Cytokine Biomarkers in Hospitalized Patients with Community Acquired Pneumonia

Joseph Pierre, Oguz Akbilgic, Heather Smallwood, Xueyuan Cao, Elizabeth Fitzpatrick, Senen Pena, Stephen Furmanek, Julio Ramirez, Colleen Jonsson,

Abstract Pneumonia is the leading cause of infectious related death costing 12 billion dollars annually in the United States alone. Despite improvements in clinical care, total mortality remains around 4%, with inpatient mortality reaching 5-10%. For unknown reasons, mortality risk remains high even after hospital discharge and there is a ... Read more >>

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Fueling influenza and the immune response: Implications for metabolic reprogramming during influenza infection and immunometabolism.

Azadeh Bahadoran, Lavanya Bezavada, Heather S Smallwood,

Recent studies support the notion that glycolysis and oxidative phosphorylation are rheostats in immune cells whose bioenergetics have functional outputs in terms of their biology. Specific intrinsic and extrinsic molecular factors function as molecular potentiometers to adjust and control glycolytic to respiratory power output. In many cases, these potentiometers are ... Read more >>

Immunol. Rev. (Immunological reviews)
[2020, 295(1):140-166]

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Dynamic metabolic reprogramming in dendritic cells: an early response to influenza infection that is essential for effector function

Svetlana Rezinciuc, Lavanya Bezavada, Azadeh Bahadoran, Susu Duan, Ruoning Wang, Daniel Lopez-Ferrer, Erika Zink, David Finklestein, Douglas Green, Ljiljana Pasa-Tolic, Paul Thomas, Heather Smallwood,

Abstract Infection with the influenza virus triggers an innate immune response aimed at initiating the adaptive response to halt viral replication and spread. However, the metabolic response fueling the molecular mechanisms underlying changes in innate immune cell homeostasis remain undefined. Thus, we compared the metabolic response of dendritic cells to ... Read more >>

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Targeting Metabolic Reprogramming by Influenza Infection for Therapeutic Intervention.

Heather S Smallwood, Susu Duan, Marie Morfouace, Svetlana Rezinciuc, Barry L Shulkin, Anang Shelat, Erika E Zink, Sandra Milasta, Resha Bajracharya, Ajayi J Oluwaseum, Martine F Roussel, Douglas R Green, Ljiljana Pasa-Tolic, Paul G Thomas,

Influenza is a worldwide health and financial burden posing a significant risk to the immune-compromised, obese, diabetic, elderly, and pediatric populations. We identified increases in glucose metabolism in the lungs of pediatric patients infected with respiratory pathogens. Using quantitative mass spectrometry, we found metabolic changes occurring after influenza infection in ... Read more >>

Cell Rep (Cell reports)
[2017, 19(8):1640-1653]

Cited: 16 times

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Pharmacologic activation of estrogen receptor β increases mitochondrial function, energy expenditure, and brown adipose tissue.

Suriyan Ponnusamy, Quynh T Tran, Innocence Harvey, Heather S Smallwood, Thirumagal Thiyagarajan, Souvik Banerjee, Daniel L Johnson, James T Dalton, Ryan D Sullivan, Duane D Miller, Dave Bridges, Ramesh Narayanan,

Most satiety-inducing obesity therapeutics, despite modest efficacy, have safety concerns that underscore the need for effective peripherally acting drugs. An attractive therapeutic approach for obesity is to optimize/maximize energy expenditure by increasing energy-utilizing thermogenic brown adipose tissue. We used in vivo and in vitro models to determine the role of ... Read more >>

FASEB J. (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2017, 31(1):266-281]

Cited: 8 times

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Seasonal influenza vaccination is the strongest correlate of cross-reactive antibody responses in migratory bird handlers.

Christine M Oshansky, Sook-San Wong, Trushar Jeevan, Heather S Smallwood, Richard J Webby, Shira C Shafir, Paul G Thomas,

UNLABELLED:Avian species are reservoirs of influenza A viruses and could harbor viruses with significant pandemic potential. We examined the antibody and cellular immune responses to influenza A viruses in field or laboratory workers with a spectrum of occupational exposure to avian species for evidence of zoonotic infections. We measured the ... Read more >>

mBio (mBio)
[2014, 5(6):e02107]

Cited: 5 times

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Diverse heterologous primary infections radically alter immunodominance hierarchies and clinical outcomes following H7N9 influenza challenge in mice.

Susu Duan, Victoria A Meliopoulos, Jennifer L McClaren, Xi-Zhi J Guo, Catherine J Sanders, Heather S Smallwood, Richard J Webby, Stacey L Schultz-Cherry, Peter C Doherty, Paul G Thomas,

The recent emergence of a novel H7N9 influenza A virus (IAV) causing severe human infections in China raises concerns about a possible pandemic. The lack of pre-existing neutralizing antibodies in the broader population highlights the potential protective role of IAV-specific CD8(+) cytotoxic T lymphocyte (CTL) memory specific for epitopes conserved ... Read more >>

PLoS Pathog. (PLoS pathogens)
[2015, 11(2):e1004642]

Cited: 10 times

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Distinct epigenetic signatures delineate transcriptional programs during virus-specific CD8(+) T cell differentiation.

Brendan E Russ, Moshe Olshanksy, Heather S Smallwood, Jasmine Li, Alice E Denton, Julia E Prier, Angus T Stock, Hayley A Croom, Jolie G Cullen, Michelle L T Nguyen, Stephanie Rowe, Matthew R Olson, David B Finkelstein, Anne Kelso, Paul G Thomas, Terry P Speed, Sudha Rao, Stephen J Turner,

The molecular mechanisms that regulate the rapid transcriptional changes that occur during cytotoxic T lymphocyte (CTL) proliferation and differentiation in response to infection are poorly understood. We have utilized ChIP-seq to assess histone H3 methylation dynamics within naive, effector, and memory virus-specific T cells isolated directly ex vivo after influenza A virus ... Read more >>

Immunity (Immunity)
[2014, 41(5):853-865]

Cited: 66 times

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Calmodulin mediates DNA repair pathways involving H2AX in response to low-dose radiation exposure of RAW 264.7 macrophages.

Heather S Smallwood, Daniel Lopez-Ferrer, P Elis Eberlein, David J Watson, Thomas C Squier,

Understanding the molecular mechanisms that modulate macrophage radioresistance is necessary for the development of effective radiation therapies, as tumor-associated macrophages promote both angiogenesis and matrix remodeling that, in turn, enhance tumor metastasis. In this respect, we have identified a dose-dependent increase in the abundance (i.e., expression level) of the calcium ... Read more >>

Chem. Res. Toxicol. (Chemical research in toxicology)
[2009, 22(3):460-470]

Cited: 3 times

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Identification of a denitrase activity against calmodulin in activated macrophages using high-field liquid chromatography--FTICR mass spectrometry.

Heather S Smallwood, Natacha M Lourette, Curt B Boschek, Diana J Bigelow, Richard D Smith, Ljiljana Pasa-Tolić, Thomas C Squier,

We have identified a denitrase activity in macrophages that is upregulated following macrophage activation, which is shown by mass spectrometry to recognize nitrotyrosines in the calcium signaling protein calmodulin (CaM). The denitrase activity converts nitrotyrosines to their native tyrosine structure without the formation of any aminotyrosine. Comparable extents of methionine ... Read more >>

Biochemistry (Biochemistry)
[2007, 46(37):10498-10505]

Cited: 30 times

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Loss of the calmodulin-dependent inhibition of the RyR1 calcium release channel upon oxidation of methionines in calmodulin.

Curt B Boschek, Terry E Jones, Heather S Smallwood, Thomas C Squier, Diana J Bigelow,

The oxidation of methionines in calmodulin (CaM) can affect the activity of calcium pumps and channels to modulate the amplitude and duration of calcium signals. We have therefore investigated the possible oxidation of CaM in skeletal muscle and its effect on the CaM-dependent regulation of the RyR1 calcium release channel. ... Read more >>

Biochemistry (Biochemistry)
[2008, 47(1):131-142]

Cited: 9 times

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High-affinity and cooperative binding of oxidized calmodulin by methionine sulfoxide reductase.

Yijia Xiong, Baowei Chen, Heather S Smallwood, Ramona J Bieber Urbauer, Lye Meng Markille, Nadezhda Galeva, Todd D Williams, Thomas C Squier,

Methionines can play an important role in modulating protein-protein interactions associated with intracellular signaling, and their reversible oxidation to form methionine sulfoxides [Met(O)] in calmodulin (CaM) and other signaling proteins has been suggested to couple cellular redox changes to protein functional changes through the action of methionine sulfoxide reductases (Msr). ... Read more >>

Biochemistry (Biochemistry)
[2006, 45(49):14642-14654]

Cited: 14 times

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Increases in calmodulin abundance and stabilization of activated inducible nitric oxide synthase mediate bacterial killing in RAW 264.7 macrophages.

Heather S Smallwood, Liang Shi, Thomas C Squier,

The rapid activation of macrophages in response to bacterial antigens is central to the innate immune system that permits the recognition and killing of pathogens to limit infection. To understand regulatory mechanisms underlying macrophage activation, we have investigated changes in the abundance of calmodulin (CaM) and iNOS in response to ... Read more >>

Biochemistry (Biochemistry)
[2006, 45(32):9717-9726]

Cited: 8 times

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Proteomic analysis of Salmonella enterica serovar typhimurium isolated from RAW 264.7 macrophages: identification of a novel protein that contributes to the replication of serovar typhimurium inside macrophages.

Liang Shi, Joshua N Adkins, James R Coleman, Athena A Schepmoes, Alice Dohnkova, Heather M Mottaz, Angela D Norbeck, Samuel O Purvine, Nathan P Manes, Heather S Smallwood, Haixing Wang, John Forbes, Philippe Gros, Sergio Uzzau, Karin D Rodland, Fred Heffron, Richard D Smith, Thomas C Squier,

To evade host resistance mechanisms, Salmonella enterica serovar Typhimurium (STM), a facultative intracellular pathogen, must alter its proteome following macrophage infection. To identify new colonization and virulence factors that mediate STM pathogenesis, we have isolated STM cells from RAW 264.7 macrophages at various time points following infection and used a ... Read more >>

J. Biol. Chem. (The Journal of biological chemistry)
[2006, 281(39):29131-29140]

Cited: 83 times

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Functional link between TNF biosynthesis and CaM-dependent activation of inducible nitric oxide synthase in RAW 264.7 macrophages.

Thomas J Weber, Heather S Smallwood, Loel E Kathmann, Lye Meng Markillie, Thomas C Squier, Brian D Thrall,

Inflammatory responses stimulated by bacterial endotoxin LPS involve Ca2+-mediated signaling, yet the cellular sensors that determine cell fate in response to LPS remain poorly understood. We report that exposure of RAW 264.7 macrophage-like cells to LPS induces a rapid increase in CaM abundance, which is associated with the modulation of ... Read more >>

Am. J. Physiol., Cell Physiol. (American journal of physiology. Cell physiology)
[2006, 290(6):C1512-20]

Cited: 14 times

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Mediating molecular recognition by methionine oxidation: conformational switching by oxidation of methionine in the carboxyl-terminal domain of calmodulin.

Asokan Anbanandam, Ramona J Bieber Urbauer, Ryan K Bartlett, Heather S Smallwood, Thomas C Squier, Jeffrey L Urbauer,

The C-terminus of calmodulin (CaM) functions as a sensor of oxidative stress, with oxidation of methionine 144 and 145 inducing a nonproductive association of the oxidized CaM with the plasma membrane Ca(2+)-ATPase (PMCA) and other target proteins to downregulate cellular metabolism. To better understand the structural underpinnings and mechanism of ... Read more >>

Biochemistry (Biochemistry)
[2005, 44(27):9486-9496]

Cited: 25 times

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Calmodulin involvement in stress-activated nuclear localization of albumin in JB6 epithelial cells.

Thomas J Weber, Sewite Negash, Heather S Smallwood, Kenneth S Ramos, Brian D Thrall, Thomas C Squier,

We report that albumin is translocated to the nucleus in response to oxidative stress. Prior measurements have demonstrated that in concert with known transcription factors albumin binds to an antioxidant response element, which controls the expression of glutathione S-transferase and other antioxidant enzymes that function to mediate adaptive cellular responses ... Read more >>

Biochemistry (Biochemistry)
[2004, 43(23):7443-7450]

Cited: 4 times

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Selective nitration of Tyr99 in calmodulin as a marker of cellular conditions of oxidative stress.

Heather S Smallwood, Nadezhda A Galeva, Ryan K Bartlett, Ramona J Bieber Urbauer, Todd D Williams, Jeffrey L Urbauer, Thomas C Squier,

We examined the possible role of methionines as oxidant scavengers that prevent the peroxynitrite-induced nitration of tyrosines within calmodulin (CaM). We used mass spectrometry to investigate the reactivity of peroxynitrite with CaM at physiological pH. The possible role of methionines in scavenging peroxynitrite (ONOO-) was assessed in wild-type CaM and ... Read more >>

Chem. Res. Toxicol. (Chemical research in toxicology)
[2003, 16(1):95-102]

Cited: 9 times

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Oxidation of Met144 and Met145 in calmodulin blocks calmodulin dependent activation of the plasma membrane Ca-ATPase.

Ryan K Bartlett, Ramona J Bieber Urbauer, Asokan Anbanandam, Heather S Smallwood, Jeffrey L Urbauer, Thomas C Squier,

Methionine oxidation in calmodulin (CaM) isolated from senescent brain results in an inability to fully activate the plasma membrane (PM) Ca-ATPase, which may contribute to observed increases in cytosolic calcium levels under conditions of oxidative stress and biological aging. To identify the functional importance of the oxidation of Met(144) and ... Read more >>

Biochemistry (Biochemistry)
[2003, 42(11):3231-3238]

Cited: 51 times

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