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The University of Southampton
Medicine

Epigenetics

Epigenetics refers to processes that induce heritable changes in gene expression without altering the gene sequence. The major epigenetic processes are DNA methylation, histone modification and miRNAs. There is now substantial evidence that alterations in these processes lead to human disease.

Our research at Southampton in epigenetics extends from the basic biology of how these epigenetic processes regulate gene expression through to their role in human disease. In particular, research is focussed on understanding how aberrant DNA methylation can lead to congenital disorders such as Beckwith-Wiedemann syndrome and Silver-Russell syndrome, and the role of epigenetic processes in the developmental origins of adult diseases (heart disease, obesity, type II diabetes, asthma, osteoarthritis  and cancer). Understanding how alterations in these epigenetic processes may lead or predispose to disease is crucial not only for the early identification of individuals at increased risk but also for the development of new strategies for intervention and treatment.


Current epigenetic research

Identification of epigenetic biomarkers for adult disease (EpiGen Consortium).

This academic consortium is comprised of researchers from University of Southampton, Liggins Institute, University of Auckland, AgResearch New Zealand, the Medical Research Council and the Singapore Institute of Clinical Sciences.  Working together with the MRC Lifecourse Epidemiology Unit and the Southampton NHIR Biomedical Research Unit in Nutrition, Diet and Lifestyle the aim of EpiGen (led in the UK by Professor Mark Hanson, Professor Keith Godfrey, Professor Cyrus Cooper, Dr Graham Burdge and Dr Karen Lillycrop) is to translate basic research in epigenetics into biomarkers and interventions to reduce the burden of non-communicable disease.  In the UK, this translational research is centred around the Southampton Women's Survey.


Epigenetic processes in the early life origins of adult disease; the role of epigenetic  processes (DNA methylation, histone modifications and small interfering RNAs) in the induction and persistence of induced changes in the physiology of the offspring.
Dr Graham Burdge and Dr Karen Lillycrop (FENS)

Developmental origins of cancer
Dr Karen Lillycrop (FENS), Dr Graham Burdge , Professor Alan Jackson

Transgenerational inheritance of altered epigenetic marks and phenotype.
Dr Graham Burdge , Dr Karen Lillycrop (FNES), Professor Mark Hanson

Early epigenetic mechanisms in bone disease and identification of epigenetic biomarkers:
Professor Cyrus Cooper , Dr Nicholas Harvey , Professor Keith Godfrey , Dr Graham Burdge , Dr Karen Lillycrop (FNES), Professor Mark Hanson , Dr Sheila Barton

The epigenetic mechanisms underlying the developmental origins of musculoskeletal disorders throughout the lifecourse
Dr Stuart Lanham, Professor Richard OC Oreffo (Bone and Joint)

Role of epigenetics in  musculoskeletal stem cell differentiation and proliferation; and thereby to enhance understanding of disease mechanisms and to inform regenerative therapeutic strategies for these disorders
Dr Stuart Lanham, Professor Richard OC Oreffo

The epigenetic regulation of placental nutrient transport
Dr Jane Cleal , Dr Rohan Lewis , Professor Mark Hanson , Dr Karen Lillycrop (FNES), Dr Nicholas Harvey , Professor Cyrus Cooper , Professor Keith Godfrey

Transgenerational epigenetic inheritance of allergy in a multigenerational cohort
Professor  John Holloway , Hasan Arshad , Wilfried Karmaus and Hongmei Zhang
(University of Carolina),
Susan Ewart (Michigan State University)

Comparison of methylation patterns of DNA from buccal cells, peripheral blood lymphocytes and nasal and airway epithelial cells of children with atopic and non-atopic asthma.
Seif Shaheen and Vardhman Rakyan (QMUL), Andy Bush (Imperial), John Henderson, John Holloway

Epigenetic Toxicity: a novel mechanism for paracetamol toxicity in asthma
John Holloway , Jane Warner , Tony Sampson

The effect of early life nutrition on  growth, cardiovascular function, metabolism and epigenetic gene regulation in sheep
Lucy Green , Kirsten  Poore , Karen Lillycrop (FNES) and Graham Burdge

Effect of embryo environment mediated through maternal nutrition, embryo culture environment or maternal health on short- and long-term development. Effect on epigenetic processes associated with (i) embryo morphogenesis, metabolism, physiology and growth (ii) embryonic stem cell phenotype and potential (iii) extraembryonic lineage development, placentation, and maternal-fetal transport capacity (iv) fetal and postnatal growth, physiology and health across organ systems
Tom Fleming (FNES), Judith Eckert , Neil Smyth (FNES)

Transient neonatal diabetes & imprinting disorders:  the Wessex Imprinting group
Deborah Mackay , Karen Temple

Genomic imprinting is the restriction of gene expression potential according to parent of origin, and this is marked not by DNA sequence variation but epigenetically, through chromatin modifications, non-coding RNA species, and particularly DNA methylation.  Approximately 100 imprinted genes are known in humans.  They are functionally hemizygous and exquisitely sensitive to changes in gene dosage caused by either genetic and epigenetic mutation, which cause a clinically-recognised spectrum of human disorders.

In the research project " Imprinting disorders - finding out why ", the Wessex Imprinting group is investigating causes and consequences of imprinting disorders, aiming to discover the biology underlying imprinting, and to improve diagnosis and management for patients

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