Professor Chris F Inglehearn

Profile

My career in human genetics began when I was awarded a Wellcome Trust Senior Basic Biomedical Fellowship at the Institute Of Ophthalmology, UCL 1992-7. After 5 years there I moved to the School of Medicine, University of Leeds, with a renewed Wellcome Fellowship, becoming Professor of Molecular Ophthalmology in February 2001. In Leeds I established the Leeds Vision Research Group and later the Division of Molecular Medicine, of which I am head. My current research interests include diseases affecting vision, tooth development and an brain function.

My group uses the techniques of genetics and genomics, including next generation and third generation sequencing technologies, bioinformatics, cell and molecular biology, genome editing and stem cell research, to determine the genetic and functional basis of a range of inherited disorders. We collaborate widely with other groups at the national and international levels, including being leading members of the UK and European Retinal Disease consortia and members of the UK 100,000 genomes “Eyes and ears” Clinical Interpretation panel.

From 2013-2017 I was the coordinator of the EyeTN EU Initial Training Network, which hosted 12 PhD students across 7 European laboratories. In all, I have supervised 30 PhD students to successful completion of their studies and have written or co-authored over 213 research papers on human inherited blindness, enamel defects and brain disorders.  

Responsibilities

• Head of Division of Molecular Medicine

Research interests

Leeds Vision Research Group; The work of the retinal disease group begins with identifying the proteins which, when defective, give rise to Mendelian diseases affecting the retina. These conditions include retinitis pigmentosa (RP), Cone-Rod Dystrophy (CRD) and Leber Congenital Amaurosis, as well as many rarer conditions and syndromes involving defects of the retina and other body systems. We also study ageing macular dystrophy (AMD), a retinal condition with both genetic and environmental causes.

Once genetic causes are identified, we use cellular and animal models, genome editing and in-silico modelling to determine the mechanisms involved and identify possible therapeutic strategies. One major strand of this work has been the discovery, first made in Leeds in 2000, of an unexpected link between mutations in ubiquitously expressed splicing factors and the inherited blindness Retinitis pigmentosa.

These and other findings have led to over 150 peer-reviewed papers in leading science journals such as Nature Genetics, American Journal Of Human Genetics, Nature Structural Biology and Human Molecular Genetics. Much of this work is now carried out in collaboration with UK and international consortia such as the UK RP Genome Project and European Retinal Disease Consortium. In addition, we collaborate with the Yorkshire Regional Genetics Service and other genetic testing laboratories to translate findings into diagnostic tests for patient benefit.

Leeds Dental Genetics Group; An early interest in syndromic conditions affecting retinal and dental development (Jalili and Heimler syndromes) led to a new research interest in dental genetics, in collaboration with colleagues in the Leeds School of Dentistry. Work in particularly focussed on the inherited condition Amelogenesis Imperfecta (AI). AI is an incurable inherited disorder in which the dental enamel is malformed, and results from mutations in over 30 genes, around half of them discovered by the group here in Leeds.

In all we have identified 14 genes implicated in syndromic and non-syndromic forms of AI, as well as creating the first comprehensive AI mutation database and developing the first UK AI diagnostic screening service in collaboration with the NHS Yorkshire Regional Genetics Service. Once the causes are know we study detailed tooth morphology and physiology, and examine appropriate animal and cellular models to determine the functional basis of the defect. This work has led to over 20 papers in the last ten years, including several in the leading genetics journals Human Molecular Genetics and American Journal Of Human Genetics. Our aim is to fully understand the processes and pathways affected by AI in order to facilitate an individualised approach to treatment and to facilitate the development of new therapies.

Leeds Psychosis Research Group; The Leeds Psychosis research group is a cross-faculty collaboration between researchers from the Faculties of Medicine and Biological Sciences, together with psychiatrists from the Leeds and York Partnership NHS Foundation Trust. This collaboration began with the premise that schizophrenia, though genetically complex, might in a few cases result from mutations of large effect that are largely Mendelian in action; and that any such alleles with recessive effect will be enriched in familial cases drawn from populations with a high level of consanguinity.

Research has focussed on several local multiplex families with a high level of consanguinity, and the group have also carried out epidemiological studies of disease burden in a local consanguineous population. In a collaboration with Qatari Psychiatrists, we screened a cohort of Arab families and cases, while in collaboration with Omani geneticists we carried out genetic screening in families with an intellectual disability.

Qualifications

• BSc Biological Sciences; 2:1 (Hons), University of Edinburgh; July 1984.
• PhD in Molecular Genetics; University of Edinburgh; July 1988.

Professional memberships

• Yorkshire Eye Research Advisory Board; 2000 - 2014
• Chair, Candlelighters Science Advisory Board; 2003 - 2010
• Wellcome Trust Molecular and Cellular Neurosciences Panel; 2004-08
• Guide Dogs for the Blind Ophthalmic Research Advisory Group; 2000-07
• National Eye Research Centre Scientific Advisory Committee; 2015 - 2021
• Fight For Sight Grant Assessment Panel; 2018 - present
• Chair of Management Group, European Retinal Disease Consortium, 2018-2021
• Member of the Genomics England Clinical Interpretation Partnership (GeCIP) Domain for Hearing and Sight

Student education

I lecture and run small group teaching sessions on human inherited diseases with medical undergraduates in their second year. I also act as a personal tutor to medical undergraduates in their first and second years. In addition I deliver lectures, tutorials and small group teaching with MSc students, again in the area of human inherited diseases, taking and interpreting family trees and multifactorial inherited diseases. 

Finally I have extensive experience of PhD supervision having supervised 30 PhDs to successful conclusion of their studies.

Research groups and institutes

• Leeds Institute of Medical Research at St James's
• Mental health