Rahman Group

image of professor shamima rahman's research group

Mitochondrial Research Group

Our Mitochondrial Research Group 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.

Main Funding: GOSHCC, The Lily Foundation

Our current work 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.

1. 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.

2. 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.

Recent references

  •  Rahman J, Rahman S. Mitochondrial medicine in the omics era. Lancet. 2018 Jun. 23;391(10139):2560-2574. doi: 10.1016/S0140-6736(18)30727-X. Epub 2018 Jun 18. Review. PubMed PMID: 29903433.

  • Keshavan N, Rahman S. Natural history of mitochondrial disorders: a systematic review. Essays Biochem. 2018 Jul 20;62(3):423-442. doi: 10.1042/EBC20170108. Print 2018 Jul 20. Review. PubMed PMID: 29980629.

  • Raman S, Chentouf L, DeVile C, Peters MJ, Rahman S. Near infrared spectroscopy with a vascular occlusion test as a biomarker in children with mitochondrial and  other neuro-genetic disorders. PLoS One. 2018 Jul 3;13(7):e0199756. doi: 10.1371/journal.pone.0199756. eCollection 2018. PubMed PMID: 29969469; PubMed Central PMCID: PMC6029804.

  • Rahman J, Noronha A, Thiele I, Rahman S. Leigh map: A novel computational diagnostic resource for mitochondrial disease. Ann Neurol. 2017 Jan;81(1):9-16. doi: 10.1002/ana.24835. PubMed PMID: 27977873; PubMed Central PMCID: PMC5347854.

  • Hikmat O, Tzoulis C, Chong WK, Chentouf L, Klingenberg C, Fratter C, Carr LJ, Prabhakar P, Kumaraguru N, Gissen P, Cross JH, Jacques TS, Taanman JW, Bindoff LA, Rahman S. The clinical spectrum and natural history of early-onset diseases due to DNA polymerase gamma mutations. Genet Med. 2017 Nov;19(11):1217-1225. doi: 10.1038/gim.2017.35. Epub 2017 Apr 27. PubMed PMID: 28471437.

  • Davison JE, Rahman S. Recognition, investigation and management of mitochondrial disease. Arch Dis Child. 2017 Nov;102(11):1082-1090. doi: 10.1136/archdischild-2016-311370. Epub 2017 Jun 24. Review. PubMed PMID: 28647693.

  • Parikh S, Goldstein A, Karaa A, Koenig MK, Anselm I, Brunel-Guitton C, Christodoulou J, Cohen BH, Dimmock D, Enns GM, Falk MJ, Feigenbaum A, Frye RE, Ganesh J, Griesemer D, Haas R, Horvath R, Korson M, Kruer MC, Mancuso M, McCormack S, Raboisson MJ, Reimschisel T, Salvarinova R, Saneto RP, Scaglia F, Shoffner J, Stacpoole PW, Sue CM, Tarnopolsky M, Van Karnebeek C, Wolfe LA, Cunningham ZZ, Rahman S, Chinnery PF. Patient care standards for primary mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society. Genet Med. 2017 Dec;19(12). doi: 10.1038/gim.2017.107. Epub 2017 Jul 27. Review. PubMed PMID: 28749475.

  • Chow J, Rahman J, Achermann JC, Dattani MT, Rahman S. Mitochondrial disease and endocrine dysfunction. Nat Rev Endocrinol. 2017 Feb;13(2):92-104. doi: 10.1038/nrendo.2016.151. Epub 2016 Oct 7. Review. PubMed PMID: 27716753.

  • Kanabus M, Fassone E, Hughes SD, Bilooei SF, Rutherford T, Donnell MO, Heales SJR, Rahman S. The pleiotropic effects of decanoic acid treatment on mitochondrial function in fibroblasts from patients with complex I deficient Leigh syndrome. J Inherit Metab Dis. 2016 May;39(3):415-426. doi: 10.1007/s10545-016-9930-4. Epub 2016 Apr 14. PubMed PMID: 27080638; PubMed Central PMCID: PMC4851692.

  • Wedatilake Y, Niazi R, Fassone E, Powell CA, Pearce S, Plagnol V, Saldanha JW, Kleta R, Chong WK, Footitt E, Mills PB, Taanman JW, Minczuk M, Clayton PT, Rahman S. TRNT1 deficiency: clinical, biochemical and molecular genetic features. Orphanet J Rare Dis. 2016 Jul 2;11(1):90. doi: 10.1186/s13023-016-0477-0. PubMed PMID: 27370603; PubMed Central PMCID: PMC4930608.

Principal Investigator 

Professor Shamima Rahman - UCL Profiles page 

Shamima Rahman

Contact us

 Section staff list

Molecular Basis of Rare Diseases Section
UCL Great Ormond Street Institute of Child Health
30 Guilford Street
London
WC1N 1EH