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Department of Physiology, Development and Neuroscience

 

Research

My research is in Fetal and Neonatal Physiology and in Developmental Programming, broad fields of Reproduction. There are three main strands to my research programmes, each of which uses an integrative approach at the whole animal, isolated organ, cellular and molecular levels to ask focused questions on the roles of fetal oxygenation in cardiovascular development.

Fetal brain sparing during hypoxia

A serious problem in pregnancy is reduced oxygen delivery to the unborn child (fetal hypoxia).  Understanding the mechanisms which underpin the fetal defence to hypoxia is therefore fundamental to developing prevention and treatment of adverse outcomes.  In response to hypoxia, the fetus redistributes its cardiac output away from peripheral circulations and towards the brain - the so called brain sparing effect.  We made the discovery that fetal brain-sparing is triggered exclusively by a carotid chemoreflex. While the field understood that the mechanisms driving this cardiovascular defence to hypoxia included neural and endocrine components, my research group also discovered that nitric oxide (NO) and reactive oxygen species (ROS) are involved.  The net fetal brain-sparing response to hypoxia thus represents the balance between neural, endocrine and local redox mechanisms.

Perinatal glucocorticoid therapy and fetal cardiovascular function

The second strand of my research investigates how the fetal defence to hypoxia may be modified by the intrauterine environment, triggering beneficial as well as detrimental consequences. We have shown that the fetal cardiovascular defence to hypoxia matures with advancing gestation together with the prepartum surge in fetal cortisol.  This maturational effect can be mimicked by treating the preterm fetus with exogenous glucocorticoids in human clinical doses.  The law in the UK, Canada, USA and Australia states that women at risk of preterm labour should be treated with exogenous glucocorticoids to accelerate fetal lung maturation.  Obstetric practice worldwide now appreciates that this treatment also accelerates maturation of the fetal cardiovascular system in addition to the fetal lung.

Prenatal hypoxia and developmental programming of cardiovascular disease

Intrauterine growth restriction (IUGR) is one of the greatest killers in obstetrics today.  It is also associated with the developmental programming of heart disease in adulthood. The third strand of my research has pioneered the contribution of chronic fetal hypoxia and oxidative stress to IUGR and the developmental programming of heart disease in complicated pregnancy, giving the UK an international lead in the subject.  We isolated the role of chronic fetal hypoxia in promoting IUGR and a prenatal origin of cardiometabolic disease in animals and in humans.  For instance, in human populations in Bolivia, we have shown that despite greater poverty, Andean ancestry confers graded protection against fetal growth restriction in pregnancy at high altitude.  Most recently, we have made the exciting discovery that the mechanism promoting adverse outcomes in the offspring of hypoxic pregnancy is oxidative stress in the fetal heart and circulation, thereby identifying potential targets for intervention.

Combined, therefore, our research programmes have components of basic, clinical, anthropological and translational science with direct relevance to cardiovascular and perinatal medicine.

Collaborators

Professor Sue Ozanne
Professor Abigail Fowden
Professor Anne Ferguson Smith
Professor Anibal Llanos
Professor Graham Burton
Professor Jin Ma
Dr Mike Murphy
Dr Andrew Murray
Dr Emilio Herrera
Dr Bernardo Krause
Dr Catherine Aiken

Postdocs

Dr Youguo Niu
Dr Kim Botting

Publications

Key publications: 

Brain KL, Allison BJ, Niu Y, Cross CM, Itani N, Kane AD, Herrera EA, Skeffington KL, Botting KJ, Giussani DA, (2019), Intervention against hypertension in the next generation programmed by developmental hypoxia, PLoS Biology 17(1): e2006552

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, 972-978

Shaw CJ, Civale J, Botting KJ, Niu Y, ter Haar G, Rivens I, Giussani DA, Lees CC, (2016), Non-invasive High Intensity Focused ultrasound treatment of Twin-Twin Transfusion Syndrome: a preliminary in vivo study, Sci Trans Med 8 (347), 347ra95

Allison BJ, Kaandorp JJ, Kane AD, Camm EJ, Lusbu C, Cross CM, Nevin-Dolan R, Thakor AS, Derks JB, Tarry-Adkins JL, Ozanne SE,  Giussani DA, (2016),  Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease,  FASEB J, 30(5), 1968-75

Allison BJ, Brain KL, Niu Y, Kane AD, Herrera EA, Thakor AS, Botting KL, Itani N, Cross CM, Skeffington KL, Beck C, Giussani DA, (2016), Fetal in vivo continuous cardiovascular function during chronic hypoxia, The Journal of Physiology 594(5), 1247-64

Giussani DA, Camm EJ, Niu Y, Richter HG, Blanco CE, Gottschalk R, Blake EZ, Horder KA, Thakor AS, Hansell JA, Kane AD, Wooding FBP, Cross CM, Herrera EA, (2012), Developmental programming of cardiovascular dysfunction by prenatal hypoxia and oxidative stress, PLoS ONE 7(2), e31017. News piece written in Science Magazine about this work.
This article is among the top 5% most cited PLOS ONE articles since the creation of the Journal.

Giussani DA, Salinas CE, Villena M, Blanco CE, (2007), The role of oxygen in prenatal growth: studies in the chick embryo, Journal of Physiology, 585(Pt 3), 911-7

Thakor AS, Giussani DA, (2005), The role of nitric oxide in mediating in vivo vascular responses to calcitonin gene related peptide in essential and peripheral circulations in the fetus, Circulation, 112(16):2510-6

Gardner DS, Giussani DA, (2003), Enhanced umbilical blood flow during acute hypoxemia following chronic umbilical cord compression:  a role for nitric oxide, Circulation, 108: 108(3):331-5

Gardner DS, Fowden AL, Giussani DA, (2002), Adverse intrauterine conditions diminish the fetal defense to acute hypoxia by increasing nitric oxide activity, Circulation, 106: 2278-2283

Teaching and Supervisions

Teaching: 

MVST 1A Homeostasis, MVST IB Human Reproduction, NST1A Physiology of Organisms, Part II NST Module P3: Fetal and Placental Physiology.

Professor of Developmental Cardiovascular Physiology & Medicine
Professor Dino A Giussani

Contact Details

+44 (0) 1223 333894, Fax: +44 (0) 1223 333840