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Head of Section, Professor Pia Ostergaard.

The aim of the Genomics Research Section is to understand the molecular genetics and developmental aetiology of a range of single gene disorders, syndromes and complex traits. Current areas of research lie within the analysis and interpretation of DNA variants in human disease, focusing on translational bench-to-bedside approaches. As such, principal investigators within the section work closely with associate members from across the University and St George’s University Hospitals NHS Foundation Trust. 

We study the impact of genomic variation on disease susceptibility, using multiple types of 'omics' data, including genomics, transcriptomics and proteomics to learn more about disease mechanisms. The University and the Trust are actively involved in the 100,000 Genomes Project, and the academic and clinical staff are members of the Genomics England Research Network Communities. These projects have the potential to transform the future of healthcare by improving the prediction and prevention of disease, enabling new and more accurate diagnostic tests and allowing the personalisation of drugs and treatments to specific gene variants.

We explore the function of disease-associated genes using cutting edge technologies and biological models. Using state-of-the-art molecular biology, biophysics, fluorescence and imaging approaches, we seek to understand the molecular and cellular mechanisms of health and disease. We also work closely with the Zebrafish Unit to examine developmental models of heart disease, eye disorders, ciliopathies, among others. Our research also goes hand-in-hand with undergraduate and postgraduate teaching at City St George’s.

Areas of research in genomics

Learn more about some of our researchers and the work they do by clicking each of the sections below.

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Bioinformatics

Dr Alan Pittman has a strong background in computational genetics and is one of the founding members of the virtual bioinformatics unit, which aims to support and promote the use of bioinformatics across the university. His research interests cover a wide range of human genomics, including the application of next-generation sequencing approaches to rare and common diseases, such as neurological disorders and lipoedema.

Primary lymphoedema

At City St George’s, we have developed an internationally recognised centre for lymphovascular research, led by Professor Pia Ostergaard, Dr Silvia Martin-Almedina, Professor Sahar Mansour and Professor Kristiana Gordon. Primary Lymphoedema is a rare condition that is clinically and genetically heterogeneous, characterised by swelling of the limbs or other parts of the body. Prof Ostergaard’s group has successfully identified numerous causal genes, highlighting phenotypic sub-classifications of Primary Lymphoedema to improve diagnosis and clinical management of this debilitating condition. Dr Silvia Martin-Almedina’s group looks at functionally validating the genetic findings using various in vitro cell models, to understand the molecular mechanisms of disease. The team is working on different ways of deep phenotyping lymphoedema patients and draws on colleagues’ expertise in imaging (Professor Franklyn Howe and Dr Lakshmi Ratnam) and immune profiling (Professor Derek Macallan).

Cardiovascular genetics

As a rare disease geneticist, Dr Laura Southgate specialises in the detection of risk genes for inherited vascular disorders. Through genome-wide analyses of DNA sequence variation, she has successfully identified causal genes for pulmonary arterial hypertension, Adams-Oliver syndrome and other rare diseases, highlighting several pathways important for human vascular development.

We also work closely with colleagues in the Experimental Cardiology section (Dr Marta Futema and Dr Roddy Walsh), conducting research into genetic risk factors for inherited heart diseases such as familial hypercholesterolemia (FH) and cardiomyopathies.

Mitochondrial disorders

Dr Chris Carroll seeks to understand the genetic causes of rare inherited neurological and metabolic diseases, with a focus on mitochondrial disorders. His investigations into the molecular mechanisms of inherited mitochondrial disorders have led to the identification and functional characterisation of genetic variation within the oxidative phosphorylation cascade and tricarboxylic acid (TCA) cycle.

Neurogenetics

Our neurogenetics research has a strong emphasis on identifying the genetic causes of neurodevelopmental disorders. Using whole-exome sequencing, Dr Kate Everett and Dr Chris Carroll each focus on applying analytical approaches to track down disease-causing variants. Their research further supports undergraduate and postgraduate education in Genomic Medicine.

Functional genomics

Some of the most important members of our research section are our zebrafish! Using these versatile vertebrates, we can model human genetic disorders and examine the impact of identified variation on embryonic development. Work led by Dr Dan Osborn focuses on disorders affecting the cilium, muscle, kidney and brain, whilst Dr Florencia Cavodeassi specialises in disorders of eye development.

We additionally use in vitro and gene editing approaches to assess protein function and dysregulation in genetic disease. Dr Silvia Martin-Almedina applies molecular biology techniques in cell culture models to examine genes important in Primary Lymphoedema. Using a range of proteomic approaches, research in Dr Southgate's group focuses on understanding the roles of Notch, Rho GTPase, BMP and other cellular pathways in the pathogenesis of rare vascular diseases. Similarly, Dr Carroll has developed a library of CRISPR/Cas9-mediated gene knockouts to explore the impact of mitochondrial gene dysfunction.

 

 

 

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