Prof Shamima Rahman
Professor of Paediatric Metabolic Medicine
Genetics & Genomic Medicine Dept
UCL GOS Institute of Child Health
- Joined UCL
- 1st Apr 2002
Research summary
The Mitochondrial Research Group at the UCL Great Ormond Street Institute of Child Health focuses on enhancing the outcomes for children with mitochondrial and other metabolic diseases by discovering mitochondrial disease genes, developing novel computational diagnostic strategies, and investigating therapeutic approaches where there are currently very limited, effective treatments. This work is leading to improved diagnosis and management.
The Mitochondrial Research Group's work currently focusses on the development of novel therapies for mitochondrial disease, whilst continuing our efforts to find new genetic causes and mechanisms for mitochondrial disorders presenting in childhood.
Molecular basis of mitochondrial disease
We have conducted a long-term project that has identified novel nuclear genes and gene variants responsible for human mitochondrial disease using an 'integrative genomics' approach. This includes detailed clinical and biochemical characterisation of patients (deep phenotyping), homozygosity mapping by high-throughput genotyping in consanguineous families, sequence analysis of candidate genes, high throughput 'next generation' sequencing methods, developing novel bioinformatics pipelines, and establishing multiple functional studies to prove pathogenicity of many disease-causing mutations identified in our laboratory. Using this approach we have discovered new disease genes, including a complex I assembly factor and genes needed for mitochondrial DNA maintenance, coenzyme Q10 biosynthesis and mitochondrial homeostasis. We have also elucidated new disease mechanisms such as our discovery that the JAK-STAT cytokine STAT2, a component of innate immunity, is a critical factor governing mitochondrial dynamics. We are now using multi-omics to investigate further the disease mechanisms underpinning the phenotypic complexity of mitochondrial diseases.
We have provided genetic diagnoses for hundreds of families referred from Great Ormond Street Hospital and further afield. This has increased the diagnostic rate from 5% 20 years ago to currently ~70% in a research setting. Gene discovery provides new insight into disease aetiology, which facilitates the development of new targeted therapies in the longer term.
Developing novel therapies
We have evaluated a number of small molecule therapies for mitochondrial disease, including vitamins and cofactors, decanoic acid, and nonsense readthrough agents. We are now commencing a gene therapy programme for these disorders.
Current members of the Mitochondrial Research Group at ICH
Postdoctoral research associate
Dr Elaina Maldonado
Clinical research fellow
Dr Nandaki Keshavan
PhD student
Joyeeta Rahman
Teaching summary
Professor Rahman is a Training Advisor to the Royal College of Paediatrics and Child Health. She is also a founding member of and currently Senior Advisor to the Education and Training Committee (ETAC) of the Society for the Study of Inborn Errors of Metabolism (SSIEM). She has been a key member of the ETAC committee delivering 11 annual SSIEM Academies since ETAC’s inception in 2008. This is a 4 year rolling programme which has trained physicians and biochemists from more than 50 countries across the globe in inherited metabolic disease.
Professor Rahman regularly lectures on the following UCL BSc and MSc courses:
MSc Clinical Genomics, Genetics and Rare Diseases CHLDGX05 Module, ICH
MSc Cardiovascular Science Cardiovascular Genetics module, UCL
MSc/MRes Neuromuscular Disease programme, Skeletal muscle and associated diseases module, Institute of Neurology
MSc Genomic Medicine Genomics of Common and Rare Inherited Diseases Module, QMUL
Education
- Royal College of Physicians
- Doctorate, Fellow of the Royal College of Physicians | 2011
- Royal College of Paediatrics and Child Health
- Doctorate, Fellow of the Royal College of Paediatrics and Child Health | 2008
- University College London
- Doctorate, Doctor of Philosophy | 2002
- Royal College of Physicians
- Doctorate, Member of the Royal College of Physicians | 1991
- University of Oxford
- Doctorate, Bachelor of Medicine & Bachelor of Surgery | 1988
- University of Oxford
- First Degree, Bachelor of Arts (Honours) | 1985