Professor and Honorary Consultant in Genetics and Ophthalmology, University of Manchester/Central Manchester University Hospitals NHS Foundation Trust

Strategic Director; Manchester Centre for Genomic Medicine.

Graeme is Professor of Genetics and Ophthalmology at Central Manchester University Hospitals NHS Foundation Trust. During training he undertook at DPhil with Professor Ian Craig in the Department of Biochemistry at the University of Oxford, studying the genetics of X-linked inherited ophthalmic disease. It was this period that enabled him to develop his combined subspecialty interests.

Having moved to Manchester in 1995 Graeme became a Wellcome Trust Clinician Scientist Fellow in 1997 and a Wellcome Trust Senior Research Fellow in 2002. This enabled him to focus on functional analyses of recently identified genes, defining their role in normal development as well as in the disorders studied. Graeme was the director of the NIHR Manchester Biomedical Research Centre (BRC), a specialist centre in Genetics and Developmental Medicine, from 2009-2012. Graeme lead the BRC to develop an impressive track record of translating scientific breakthroughs into clinical practice.2012-14 Graeme was the inaugural director of the Institute of Human Development, within the Faculty of Medical and Human Sciences at The University of Manchester helping to bring together research in the areas of genetic medicine, specialist senses, diabetes & endocrinology, maternal and fetal health and paediatrics.

Graeme’s major research interest is the investigation of genetic disorders associated with visual disability. His overaching aims are to improve the diagnosis, management and treatment of such conditions. This work initially focused on the characterisation of genes and proteins underlying inherited developmental disorders such as anophthalmia, cataract and retinal degenerative disorders. However most recently Graeme has overseen a scientific team that provides genetic testing for inherited opthalmic disease. This includes retinoblastoma, the commonest ocular malignancy of childhood. Furthermore, through funding provided by the Department of Health and the British Retinitis Pigmentosa Society his team has developed a national genetic testing service for inherited retinal diseases. These include several forms of retinitis pigmentosa, cone-rod dystrophy as well as a number of macular dystrophies.

As an academic clinician, I am intent on adopting genomics into mainstream healthcare for rare eye disease. I have made contributions that span the translational spectrum from basic science, through fundamental understanding of major causes of childhood and adult visual disability, to innovative clinical services delivery. I believe that a complementary expertise in detailed diagnostic classification (’deep phenotyping’) aligned to molecular discovery is able to develop novel biological insights that catalyse discovery of interacting networks and inform biological models. My work spans:

 i) Discovery; for example this has demonstrated how different mutations at a single locus can produce different diseases (e.g. Bestrophinopathies) and demonstrated what has now become well recognised, that somatic mutational mosaicism gives rise to distinct phenotypes. My work has a broad relevance including developmental eye disease (anterior segment, congenital cataract); corneal disease; inherited retinal disease; optic nerve disease and spans both children and adults.

ii) Translation; Genomic sciences are profoundly technology-driven. I manage the team that delivers diagnostic testing for retinoblastoma, congenital cataract and lens dislocation disorders, inherited retinal dystrophies. I have adopted and extending state-of-the art technologies in order to develop the efficient NGS-based diagnostic NHS diagnostic genomic services that now encompass an increasing number of diseases.  Since whole exome and whole genome sequencing (WES, WGS) are also emerging I have also focussed on increasing the bioinformatics components of this work. I believe that is important for clinical research focus to shift towards improved treatment and management; for example, I am leading an improvement science programme to develop a novel care pathway for congenital cataract and have been involved as regional lead for the recent gene therapy trial for choroideremia (publication 2).

iii) Public engagement; In developing genomic diagnostic services for inherited ophthalmic disease I have worked closely with patients and patient groups, senior genetic counsellors and visual Impairment organizations to ensure engagement and support in patient-focused Health Services research based on 2 programme grants. This has ensured that both research and clinical developments are aligned to patient need. This included working on the James Lind Alliance priority setting partnership for vision research and working closely with patient groups within the multicentre Regard study (funded by Fight for Sight; see below). Health economic  and qualitative healthcare approaches have led to innovative strategies for patient management and collaboration in clinical trials.

Outside Manchester

Dr Bart Leroy, Dept of Ophthalmology & Ctr for Medical Genetics, Ghent University Hospital, Ghent, Belgium

Professors AR Webster, Alison Hardcastle, Institute of Ophthalmology, UCL, London

Miss SM Downes, Dr Andrea Nemeth, Oxford University

Professor Chris Inglehearn, University of Leeds

Professor Les Biesecker, National Institutes of Health National, Human Genome Research Institute, Human Development Unit, Bethesda, USA

Professor Veronica van Heyningen, Dr David Fitzpatrick MRC Unit of Mammalian Genetics, Crewe Road, Edinburgh.

Within Manchester

Dr Forbes Manson

Professors Jill Clayton Smith, Chris Lloyd, Peter Clayton

British Society of Human Genetics

Fellow, Royal College of Ophthalmologists

Fellow, Academy of Medical Sciences

MA MB BCh DPhil FRCOphth

Through my work as a clinician, an academic, and also as a strategic leader, I am committed to using my position for public and societal benefit. Examples include:

My clinical interest is the evaluation of individuals with rare inherited disorders causing visual disability. I have overseen the growth of this large tertiary service since 1995 and continue to contribute to and lead services that include paediatric, retinal and general genetic ophthalmic clinics. This represents one of the largest clinical services in the UK and also links closely to ophthalmic imaging and electrodiagnostic testing. I contribute to a large multidisciplinary team encompassing clinical service, molecular diagnostics and translational research.

I co-manage the ocular genetic testing service in Manchester. Since 2004 – through grants to DH, RP Fighting blindness and Fight for Sight – I have led a team (with Dr Simon Ramsden, MCGM) that has designed, validated and delivered testing for inherited retinal dystrophies (IRD).  From 2012 we began delivering genomic testing via next generation sequencing (105 genes in 2012; 190 in 2014) and as such we were one of the first adopters into clinical practice of NGS, including overseeing the bioinformatics strategy. This service is internationally regarded and is delivered for patients across the world. The design of an NGS test for congenital cataract (CC) was launched in 2013 and also offers diagnostic testing for CC to the NHS and internationally. I also oversee the ocular molecular genetic testing service that offers testing for retinoblastoma, recently converting this NGS methodology.

I am committed to training of clinicians, allied health professionals and scientists. As part of my clinical role I have trained clinical geneticists (2 to MD, one to PhD), ophthalmologist (PhD level) and supervised attachments in genetic ophthalmologists for MSc students in Investigative Ophthalmic Vision Sciences and Genetic Counselling. Local and National clinical leadership for rare disease:

In developing genomic diagnostic services for inherited ophthalmic disease I have worked closely with patients and patient groups, senior genetic counsellors and visual Impairment organizations to ensure engagement and support in patient-focused Health Services research based on 2 programme grants. This has ensured that both research and clinical developments are aligned to patient need. This included working on the James Lind Alliance priority setting partnership for vision research.