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Paul Meakin

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BHF Intermediate Basic Science Research Fellow and University Academic Fellow, University of Leeds

Dr Paul Meakin completed his degree at the University of Nottingham, in Biochemistry and Biological Chemistry (MSci) in 2004. In 2005 he moved to the University of Dundee to undertake his PhD with Prof Mike Ashford, on the role of the beta-secretase enzyme, BACE1, in whole animal energy homeostasis. Between 2009 and 2018 Dr Meakin continued to work in Dundee working on understanding the metabolic dysregulation that occurs in a variety of diseases, including NASH, diabetes, cardiovascular disease and Alzheimer’s disease.

In 2018 Dr Meakin was awarded a BHF Basic Science Intermediate Fellowship to investigate the role of BACE1 in the development of cardiovascular complications associated with type 2 diabetes, and joined the University of Leeds as a University Academic Fellow. His research uses in-vivo (iontophoresis and laser Doppler imaging) and ex-vivo (wire myography) techniques, along with working with colleagues to translate the findings into humans.

Dr Meakin is a Metabolic physiology theme lead for The Physiology Society as well as a British Microcirculation Society Committee member.

Experience

  • 2018–present
    Senior research fellow, University of Leeds
  • 2009–2018
    Postdoctoral research associate, University of Dundee

Education

  • 2009 
    University of Dundee, PhD
  • 2004 
    University of Nottingham, MSci in Biochemistry and Biological Chemistry

Publications

  • 2020
    Elevated circulating amyloid promotes concentrations in obesity and diabetes promote vascular dysfunction. , Journal of Clinical Investigation
  • 2018
    Small vessels, dementia and chronic diseases – molecular mechanisms and pathophysiology. , Clinical Science
  • 2018
    Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of Keap1, Nature
  • 2018
    Bace1-dependent amyloid processing regulates hypothalamic leptin sensitivity in obese mice. , Scientific Reports
  • 2018
    The BACE1 product sAPPβ induces ER stress, inflammation and attenuates insulin signaling in skeletal muscle. , Metabolism
  • 2018
    The beta secretase BACE1 regulates the expression of the insulin receptor in the liver. , Nature Communications
  • 2016
    Dimethyl fumarate blocks pro-inflammatory cytokine production via inhibition of TLR induced M1 and K63 ubiquitin chain formation., Scientific Reports
  • 2015
    Neuronal development is promoted by weakened intrinsic antioxidant defenses due to epigenetic repression of Nrf2, Nature Communications
  • 2015
    Beta2-integrin knock-in mice remain glucose tolerant in spite of insulin resistance, neutrophil infiltration and inflammation. , PLoS One
  • 2015
    Prophylactic and therapeutic treatment with a synthetic analogue of a parasitic worm product prevents experimental arthritis and inhibits IL-1b production via NRF2-mediated counter-regulation of the inflammasome., Journal of Autoimmunity
  • 2014
    Nrf2 target genes can be controlled by neuronal activity in the absence of Nrf2 and astrocytes. , PNAS
  • 2014
    Antioxid Redox Phosphoinositide 3-kinases upregulate system xc- via eIF2α and ATF4 – a pathway active in glioblastomas and epilepsy. , Antioxidant & Redox Signaling
  • 2014
    The susceptibility of Nrf2-null mice to hepatic steatosis and cirrhosis upon consumption of a high-fat diet is associated with a profound disturbance in metabolic enzymes in the liver, but not with insulin resistance. , Journal of Cell Biology
  • 2014
    Altered amyloid precursor protein processing regulates glucose uptake and oxidation in cultured rodent myotubes. , Diabetologia
  • 2013
    Anorexigenic and orexigenic hormone modulation of mammalian target of rapamycin complex 1 activity and the regulation of hypothalamic agouti-related protein mRNA expression. , Neurosignals
  • 2011
    Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice. , Biochemical Journals
  • 2010
    Loss of Nrf2 markedly exacerbates nonalcoholic steatohepatitis. , Free Radical Biology and Medicine
  • 2010
    The unfolded protein response is activated in skeletal muscle by high-fat feeding: potential role in the down-regulation of protein synthesis. , American Journal of Physiology-Endocrinology and Metabolism
  • 2007
    Fructose metabolism in the adult mouse optic nerve, a central white matter tract. , Journal of Cerebral Blood Flow & Metabolism
  • 2006
    Fructose supports energy metabolism of some, but not all, axons in adult mouse optic nerve. , Journal of Neurophysiology

Grants and Contracts

  • 2020
    Identifying serum BACE1 as a novel biomarker for cardiovascular complications in Type 2 diabetes.
    Role:
    PI
    Funding Source:
    Diabetes UK
  • 2018
    What are the mechanisms involved in the beneficial effects of BACE1 inhibition on endothelial function in type 2 diabetes?
    Role:
    PI
    Funding Source:
    British Heart Foundation
  • 2016
    Is plasma amyloid a useful biomarker for metabolic disease?
    Role:
    co-I
    Funding Source:
    Diabetes Research & Wellness Foundation
  • 2016
    Do plasma amyloid peptide levels link metabolic syndrome and increased risk of AD?
    Role:
    PI
    Funding Source:
    Alzheimer’s Research UK
  • 2015
    BACE1 and endothelial dysfunction in diabetes.
    Role:
    co-I
    Funding Source:
    British Heart Foundation

Professional Memberships

  • Physiology Society
  • Biochemistry Society
  • British Microcirculation Society
  • Diabetes UK