I am a post-doctoral research associate in the Wellcome Trust Centre for Mitochondrial Research, working with Prof. Zofia Chrzanowska-Lightowlers, Prof. Robert Lightowlers and Prof. Robert Taylor. The aim of my project is to further understand the biology of mitochondrial gene expression, through characterising the molecular function of novel disease-associated proteins identified by whole exome sequencing.
My interest in this research area stems from the potential to uncover key mechanistic elements underpinning the pathogenesis of mitochondrial disorders, thereby yielding important insights into the development of new treatments to improve the health and quality of life of patients with mitochondrial diseases.
Principal Investigators: Professor Zofia Chrzanowska-Lightowlers,Professor Robert Lightowlers and Professor Rob Taylor
Other staff members involved: Professor Patrick Chinnery, Professor Rita Horvath and Dr Robert McFarland
The main focus of our research is to understand fundamental regulatory mechanisms of mitochondrial transcription and translation in human disease.
The dominant role of mitochondria is energy production in the form of adenosine-5′-triphosphate via the respiratory chain in the process called oxidative phosphorylation (OXPHOS). Mutations of genes encoding OXPHOS proteins and RNAs are a significant contributor to human mitochondrial diseases.
The human exome harbours about 85% of disease-causing mutations. The recent advances in next generation, whole-exome sequencing is allowing us to identify novel mitochondrial disease-causing genes in patients with well-defined, multiple OXPHOS deficiencies indicative of a defect in generalised mitochondrial translation. I am investigating the molecular pathology of newly-identified mitochondrial disease genes by utilizing cells and tissues derived from patients to fully characterise the defective mitochondrial phenotype.
At present there are no highly effective treatments for patients with mitochondrial respiratory chain disease. However, we hope that an increased understanding of the basic mechanistic aspects of mitochondrial gene expression will make a positive step towards the development of therapeutic strategies to prevent and treat these devastating diseases.
Sponsor/Funder: The Wellcome Trust
Using a quantitative quadruple immunofluorescent assay to diagnose isolated mitochondrial Complex I deficiency. Ahmed ST, Alston CL, Hopton S, He L, Hargreaves IP, Falkous G, Oláhová M, McFarland R, Turnbull DM, Rocha MC, Taylor RW. Sci Rep. 2017 Nov 15;7(1):15676. doi: 10.1038/s41598-017-14623-2.
Biallelic C1QBP Mutations Cause Severe Neonatal-, Childhood-, or Later-Onset Cardiomyopathy Associated with Combined Respiratory-Chain Deficiencies. Feichtinger RG, Oláhová M, Kishita Y, Garone C, Kremer LS, Yagi M, Uchiumi T, Jourdain AA, Thompson K, D’Souza AR, Kopajtich R, Alston CL, Koch J, Sperl W, Mastantuono E, Strom TM, Wortmann SB, Meitinger T, Pierre G, Chinnery PF, Chrzanowska-Lightowlers ZM, Lightowlers RN, DiMauro S, Calvo SE, Mootha VK, Moggio M, Sciacco M, Comi GP, Ronchi D, Murayama K, Ohtake A, Rebelo-Guiomar P, Kohda M, Kang D, Mayr JA, Taylor RW, Okazaki Y, Minczuk M, Prokisch H. Am J Hum Genet. 2017 Oct 5;101(4):525-538. doi: 10.1016/j.ajhg.2017.08.015. Epub 2017 Sep 21.
Pathogenic variants in HTRA2 cause an early-onset mitochondrial syndrome associated with 3-methylglutaconic aciduria. Oláhová M, Thompson K, Hardy SA, Barbosa IA, Besse A, Anagnostou ME, White K, Davey T, Simpson MA, Champion M, Enns G, Schelley S, Lightowlers RN, Chrzanowska-Lightowlers ZM, McFarland R, Deshpande C, Bonnen PE, Taylor RW. J Inherit Metab Dis. 2017 Jan;40(1):121-130. doi: 10.1007/s10545-016-9977-2. Epub 2016 Sep 30.
Biallelic Mutations in TMEM126B Cause Severe Complex I Deficiency with a Variable Clinical Phenotype. Alston CL, Compton AG, Formosa LE, Strecker V, Oláhová M, Haack TB, Smet J, Stouffs K, Diakumis P, Ciara E, Cassiman D, Romain N, Yarham JW, He L, De Paepe B, Vanlander AV, Seneca S, Feichtinger RG, Płoski R, Rokicki D, Pronicka E, Haller RG, Van Hove JL, Bahlo M, Mayr JA, Van Coster R, Prokisch H, Wittig I, Ryan MT, Thorburn DR, Taylor RW. Am J Hum Genet. 2016 Jul 7;99(1):217-27. doi: 10.1016/j.ajhg.2016.05.021. Epub 2016 Jun 30.
Alston CL, Howard C, Oláhová M, Hardy SA, He L, Murray PG, O’Sullivan S, Doherty G, Shield JP, Hargreaves IP, Monavari AA, Knerr I, McCarthy P, Morris AA, Thorburn DR, Prokisch H, Clayton PE, McFarland R, Hughes J, Crushell E, Taylor RW. J Med Genet. 2016 Sep;53(9):634-41. doi: 10.1136/jmedgenet-2015-103576. Epub 2016 Apr 18.
Oláhová M, Hardy SA, Hall J, Yarham JW, Haack TB, Wilson WC, Alston CL, He L, Aznauryan E, Brown RM, Brown GK, Morris AA, Mundy H, Broomfield A, Barbosa IA, Simpson MA, Deshpande C, Moeslinger D, Koch J, Stettner GM, Bonnen PE, Prokisch H, Lightowlers RN, McFarland R, Chrzanowska-Lightowlers ZM, Taylor RW. Brain. 2015 Dec;138(Pt 12):3503-19. doi: 10.1093/brain/awv291. Epub 2015 Oct 27.
A recessive homozygous p.Asp92Gly SDHD mutation causes prenatal cardiomyopathy and a severe mitochondrial complex II deficiency. Alston CL, Ceccatelli Berti C, Blakely EL, Oláhová M, He L, McMahon CJ, Olpin SE, Hargreaves IP, Nolli C, McFarland R, Goffrini P, O’Sullivan MJ, Taylor RW. Hum Genet. 2015 Aug;134(8):869-79. doi: 10.1007/s00439-015-1568-z. Epub 2015 May 26.
A peroxiredoxin, PRDX-2, is required for insulin secretion and insulin/IIS-dependent regulation of stress resistance and longevity. Oláhová M, Veal EA. Aging Cell. 2015 Aug;14(4):558-68. doi: 10.1111/acel.12321. Epub 2015 Mar 23.
A truncating PET100 variant causing fatal infantile lactic acidosis and isolated cytochrome c oxidase deficiency. Oláhová M, Haack TB, Alston CL, Houghton JA, He L, Morris AA, Brown GK, McFarland R, Chrzanowska-Lightowlers ZM, Lightowlers RN, Prokisch H, Taylor RW. Eur J Hum Genet. 2015 Jul;23(7):935-9. doi: 10.1038/ejhg.2014.214. Epub 2014 Oct 8.
Genome-wide screening identifies new genes required for stress-induced phase 2 detoxification gene expression in animals. Crook-McMahon HM, Oláhová M, Button EL, Winter JJ, Veal EA. BMC Biol. 2014 Aug 14;12:64. doi: 10.1186/s12915-014-0064-6.
Translating a low-sugar diet into a longer life by maintaining thioredoxin peroxidase activity of a peroxiredoxin. Veal EA, Oláhová M. Mol Cell. 2011 Sep 2;43(5):699-701. doi: 10.1016/j.molcel.2011.08.016.
A redox-sensitive peroxiredoxin that is important for longevity has tissue- and stress-specific roles in stress resistance. Oláhová M, Taylor SR, Khazaipoul S, Wang J, Morgan BA, Matsumoto K, Blackwell TK, Veal EA. Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19839-44. doi: 10.1073/pnas.0805507105. Epub 2008 Dec 8.
Effect of selenium on lipid alternations in pigment-forming yeasts. Certík, M., Breierová, E., Oláhová, M., Sajbidor, J. and Márová, Food Science and Biotechnology. 2013;22:45-51.