Karolina Krakowiak

The club cell circadian clock regulates temporal patterns in leukocyte trafficking in chronic allergic airways disease

Jafar Cain, Amlan Chakraborty, Vishvangi Deugi, Karolina Krakowiak et autres

Abstract Rationale Asthma displays temporally variable symptoms which worsen overnight, corresponding with a nocturnal increase in airway eosinophils. The molecular clock within the club cell of the bronchial epithelium is a key driver of lung rhythmic processes, however, it’s role in chronic …

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Vascular smooth muscle calcium sparks and sarcoplasmic reticulum calcium load are reduced in women with preeclampsia

Lauren A. Parnell, Anna L. Tierney, Elizabeth C. Cottrell, Karolina Krakowiak et autres

Abstract Background Maternal microvascular dysfunction is a hallmark of the hypertensive pregnancy disorder preeclampsia, but the mechanism(s) have not been defined. Historically, attention has focused on the vascular endothelium, but microvascular function is largely determined by the downstream effector, vascular smooth muscle …

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Targeting the airway epithelial cell clock in attenuating airway hyperresponsiveness associated with T2 asthma

Amlan Chakraborty, Jafar Cain, Robert J. Maidstone, Vishvangi Deugi et autres

Asthma is a highly rhythmic disease with increased airway sputum eosinophilia and decline in lung function (FEV1) observed early morning. We have previously shown that airway hyperresponsiveness (AHR) is regulated by the clock gene Reverbα. Using the Cre/Lox system, we developed mice …

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S124 Single-cell transcriptomics identifies unique pathways regulating airway hyperresponsiveness via circadian regulator Rev-erba in airway epithelium

Ashesh Chakraborty, J. R. Cain, Robert J. Maidstone, Vishvangi Deugi et autres

Introduction and Objectives Asthma exhibits diurnal variation, with symptoms worsening at night, coincident with increased airway inflammation and narrowing overnight. Our research has highlighted the role of the molecular clock in regulating airway hyperresponsiveness (AHR), a critical feature of asthma. This study …

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Airway inflammation and hyperresponsiveness in asthma is regulated by the circadian clock through REV-ERBα

Amlan Chakraborty, Jafar Cain, Robert J. Maidstone, Karolina Krakowiak et autres

Background: We have previously shown that the molecular clock protein, REV-ERBα, is important in determining time of day variation in airway hyperresponsiveness (AHR) in a Rev-erbα global knock out murine model of allergic airway disease (AAD). However, it is unclear which peripheral …

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BS64 Inhibition of phlpp phosphatases reduces vascular smooth muscle cell calcification

Samantha J. Borland, Karolina Krakowiak

Arterial medial calcification is the formation of mineralised tissue within the smooth muscle layer of the vessel wall, and is an independent risk factor for mortality in chronic kidney disease; no treatments exist. Protein kinase Cα (PKCα) belongs to the PKC family …

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Identification of diurnal rhythmic blood markers in bronchial asthma

Karolina Krakowiak, Robert J. Maidstone, Amlan Chakraborty, Alexandra C. Kendall et autres

Rationale: Asthma is a rhythmic inflammatory disease of the airway, regulated by the circadian clock. "Spill-over" of airway inflammation into the systemic circulation occurs in asthma and is reflected in circulating immune cell repertoire. The objective of the present study was to …

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Expression Of Clock Gene PER3 Is Altered In Asthma

Karolina Krakowiak, Robert J. Maidstone, John Blaikley, Polly Downton et autres

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Circadian Blood Profiling in Asthma

Karolina Krakowiak

L1 Blood immune cells clock mechanism is altered in asthma, with a time-of-day dependent response to steroids in vitro

Karolina Krakowiak, Polly Downton, John Blaikley, Hannah Jane Durrington

Asthma is a rhythmic disease, with symptoms, airway physiology and inflammation showing strong time-of-day differences. Biological rhythms in our bodies (circadian rhythms) occur through the action of clock genes, present in most cell types, including immune cell. Chronotherapy is administering a treatment …

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Circadian asthma airway responses are gated by REV-ERBα

Hannah Jane Durrington, Karolina Krakowiak, P. J. J. De Meijer, Nicola Begley et autres

Background Asthma is an inflammatory disease of the airway showing a strong time of day rhythm. Airway hyperresponsiveness is a dominant feature of asthma, but it is not known if this is under clock control. The circadian clock powerfully regulates inflammation. The …

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Cardiac mitochondrial function depends on BUD23 mediated ribosome programming

Matthew D. Baxter, Maria Voronkov, Toryn M. Poolman, Gina L. J. Galli et autres

Efficient mitochondrial function is required in tissues with high energy demand such as the heart, and mitochondrial dysfunction is associated with cardiovascular disease. Expression of mitochondrial proteins is tightly regulated in response to internal and external stimuli. Here we identify a novel …

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