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Cambridge Cardiovascular

 

Research

Developmental programming of cardiovascular and metabolic disease

The major research aims of my laboratory are to understand the mechanisms by which suboptimal growth and nutrition in early life lead to increased risk of type 2 diabetes, cardiovascular disease, obesity and premature death. This concept is terms the Developmental Origins of Health and Disease. Our goal is to use the understanding gained from mechanistic studies to develop rational intervention strategies.

To achieve our aims, we incorporate the study of both rodent models and human biopsy material (including muscle, adipose tissue and placenta) as well as studies in cell culture. The parallel approach of studies in humans and animal models has enabled us to define the fundamental molecular processes that are conserved between species and underpin developmental programming. This involves the study of changes in the transcriptome, proteome, epigenome and mitochondrial function.

A particular research interest at the moment is to understand how gestational diabetes and obesity during pregnancy impacts on the short and long-term cardio-metabolic health of the offspring. This is a global concern as in many populations over half of women and either obese or overweight during pregnancy and therefore urgent action is needed to minimise the transmission of poor cardio-metabolic health from mother to child.

TWITTER:  @ozannelab

Publications

Key publications: 

Most recent publications are listed on PubMed

Nicholas LM, Nagao M, Kusinski LC, Fernandez-Twinn DS, Eliasson L & Ozanne SE (2020) Exposure to maternal obesity programs sex differences in pancreatic islets of the offspring in mice. Diabetologia 63: 324-337

Tarry-Adkins JL, Aiken CE & Ozanne SE (2019) Neonatal, infant and childhood growth following metformin versus insulin treatment for gestational diabetes: A Systematic review and meta-analysis. PLoS Medicine 16 (8): e1002848

Niu Y, Kane AD, Lusby CM, Allison BJ, Chua YY, Kaandorp JJ, Nevin-Dolan R, Ashmore TJ, Blackmore HL, Derks JB, Ozanne SE & Giussani DA (2018) Maternal allopurinol prevents cardiac dysfunction in adult male offspring programmed by chronic hypoxia during pregnancy. Hypertension 72: 971-978

Beeson JH, Blackmore HL, Carr SK, Dearden L, Duque- Guimarães DE, Kusinski LC, Pantaleão LC, Pinnock AG, Aiken CE, Giussani DA, Fernandez-Twinn DS & Ozanne SE (2018) Maternal exercise intervention in obese pregnancy improves the cardiovascular health of the adult male offspring. Molecular Metabolism 16:35-44

Berends LM, Dearden L, Tung YCL, Voshol P, Fernandez-Twinn DS & Ozanne SE (2018) Postnatal catch-up growth programs central and peripheral insulin resistance in male mice. Diabetologia 10: 2225-34

Loche E, Blackmore HL, carpenter AAM, Beeson JH, Pinnock A, Ashmore TJ, Aiken CE, de Almeida-Faria J, Schoonejans J, Giussani DA, Fernandez-Twinn DS & Ozanne SE (2018) Maternal diet-induced obesity programmes cardiac dysfunction in male mice independently of post-weaning diet. Cardiovascular Res. 114: 1372-1374

Dearden L, Bouret SG & Ozanne SE (2018) Sex and gender differences in developmental programming of metabolism. Mol Metab 15:8-19

Lowe R, Barton C, Jenkins CA, Ernst C, Forman O, Fernandez-Twinn DS, Bock C, Rossiter SJ, Faulkes CG, Ozanne SE, Walter L, Odom DT, Mellersh C & Rakyan VK (2018) Ageing-associated DNA methylation dynamics are a molecular readout of lifespan variation among mammalian species. Genome Biology 19:22

Holland ML, Lowe R, Caton PW, Gemma C, Carbajosa G, Danson AF, Carpenter AA, Loche E, Ozanne SE & Rakyan VK (2016) Early life nutrition modulates the epigenetic state of specific rDNA genetic variants in mice. Science 353:495-8

Martin-Gronert MS, Fernandez-Twinn DS, Bushell M, Siddle K & Ozanne SE (2016) Cell autonomous programming of rat adipose tissue insulin signaling proteins by maternal nutrition. Diabetologia 59: 1266-75

Blackmore HL, Niu Y, Fernandez-Twinn DS, Tarry-Adkins JL, Giussani DA & Ozanne SE (2014) Maternal diet-induced obesity programmes cardiovascular dysfunction in adult male mouse offspring independent of current body weight. Endocrinology 155: 3970-80

Fernandez-Twinn DS, Alfaradhi MZ, Martin-Gronnert MS, Duque-Guimaraes DE, Piekarz A, Ferland-McCollough D, Bushell M & Ozanne SE (2014) Down-regulation of IRS-1 in adipose tissue of offspring of obese mice is programmed cell-autonomously through post-transcriptional mechanisms. Molecular Metabolism 3: 325-33

Tarry-Adkins JL, Blackmore HL, Martin-Gronert MS, Fernandez-Twinn DS, McConnell JM, Hargreaves IP, Giussani DA & Ozanne SE (2013) Coenyme Q10 prevents accelerated cardiac aging in a rat model of poor maternal nutrition and accelerated postnatal growth Molecular Metabolism 2: 480-90

Tarry-Adkins JL, Martin-Gronert MA, Fernandez-Twinn DS, Hargreaves I, Alfaradhi MA, Land JM, Aiken CE & Ozanne SE (2013) Poor maternal nutrition followed by accelerated postnatal growth leads to  alterations in DNA damage and repair, oxidative and nitrosative stress and oxidative defense capacity in rat heart. FASEB J 27:379-90

Fernandez-Twinn DS, Blackmore HL, Siggens L, Giussani DA, Cross CM, Foo F & Ozanne SE (2012) The programming of cardiac hypertrophy in the offspring by maternal obesity is associated with hyperinsulinemia, AKT, ERK and mTOR activation. Endocrinology 153: 5961-71

Ferland-McCollough D, Fernandez-Twinn DS, Cannell IG, David H, Warner M, Vaag AA, Bork-Jensen J, Brøns C, Gant TW, Willis AE, Siddle K, Bushell M & Ozanne SE (2012) Programming of adipose tissue miR-483-3p and GDF3 expression by maternal diet in type 2 diabetes. Cell Death Differ 19: 1003-12

Sandovici I, Smith NH, Nitert MD, Ackers-Johnson M, Uribe-Lewis S, Ito Y, Jones RH, Marquez VE, Cairns WJ, Tadayyon M, O'Neill LP, Murrell A, Ling C, Constância M & Ozanne SE (2011) Maternal diet and aging alter the epigenetic control of a promoter-enhancer interaction at the Hnf4a gene in rat pancreatic islets. PNAS 108:5449-54

 

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Professor of Developmental Endocrinology
Professor Susan  Ozanne

Affiliations

Collaborator profiles: 
Classifications: 
Person keywords: 
nutritional programming
miRNAs
gestational diabetes
maternal obesity
insulin resistance
metabolic phenotyping
maternal diet
cardio-metabolic health