Degrees

BMedSci (Hons) in Neuroscience (Newcastle); MBBS (Hons) in Medicine and Surgery (Newcastle); PhD in Molecular Genetics (Newcastle)

Awards and Prizes

Fellow of the American Neurological Association (2011)

Foulkes Foundation Medal (Academy of Medical Sciences) (2011)

National Institute for Health Research Senior Investigator (2010)

Fellow of Academy of Medical Sciences (2009)

Fellow of the Royal College of Pathologists (2007)

Fellow of the Royal College of Physicians (2006)

Research Interests

I am a practising clinical neurologist with an interest in genetic disorders of the nervous system, and particularly those caused by mitochondrial dysfunction.

Mitochondrial disorders affect approximately 1 in 4300 of the population and cause progressive, incurable diseases that often result in premature death. The primary genetic defect affects either nuclear DNA or mitochondrial DNA (mtDNA), and ultimately leads to a biochemical defect of adenosine triphosphate (ATP) synthesis. However, despite having the same basic biochemical basis, mitochondrial disorders have an enormously variable clinical presentation and disease course.

My research group is based in the MRC Mitochondrial Biology Unit on the Biomedical Campus. We aim to determine the major nuclear and mitochondrial genetic factors that modulate the clinical expression of mitochondrial disorders, thus explaining the variable phenotype.  Specifically, we are working to: (i) define the sub-cellular mechanism responsible for the mtDNA genetic bottleneck during female germ cell development; (ii) characterise novel nuclear gene defects in patients with Mendelian mitochondrial disorders; and (iii) define critical nuclear-mtDNA interactions through the investigation of homoplasmic mtDNA diseases

These three laboratory research themes dove tail into a clinical translational research programme studying the natural history of mitochondrial disease, and developing new treatments through investigator-led experimental medicine studies and clinical trials in genetically stratified patient groups.

Selected publications

Floros VI, Pyle A, Dietmann S, Wei W, Tang WWC, Irie N, Payne BAI, Capalbo A, Noli L, Coxhead J, Hudson G, Crosier M,Strahl H, Khalaf Y, Saitou M, Ilic D, Surani MA, Chinnery PF. Segregation of mitochondrial DNA heteroplasmy through a development genetic bottleneck in human embryos. Nature Cell Biology 2018 Feb;20(2):144-151. PMID: 29335530 Also see: News and Views, Nature Cell Biology 2018;20:118-126

Raymond FL, Horvath R, Chinnery PF. First-line genomic diagnosis of mitochondrial disorders. Nature Reviews Genetics 2018 Jul;19(7):399-400. PMID:29789687

Keogh MJ, Wei W, Wilson I, Coxhead J, Ryan S, Rollinson S, Griffin H, Kurzawa-Akanbi M, Santibanez-Koref M, Talbot K, Turner M, McKenzie C, Troakes C, Attems J, Smith C, Al Sarraj S, Morris CM, Ansorge O, Pickering-Brown S, Ironside JW, Chinnery PF. Genetic compendium of 1511 human brains available through the UK Medical Research Council Brain Banks Network Resource. Genome Research 2016;27(1):165-173. PMID:28003435

Chinnery PF, Zeviani M. Mitochondrial matchmaking. New England Journal of Medicine 2016;375:1894-1896. PMID:27959648

Tang WWC, Dietmann S, Irie N, Leitch HG, Floros VI, Hackett JA, Chinnery PF, Surani MA. A Unique Gene Regulatory Network of the Human Germline Resets the Epigenome for Development. Cell 2015;161(6):1453-67. PMID:26046444  PMCID: PMC4459712

Stewart JB, Chinnery PF. The dynamics of mitochondrial DNA heteroplasmy: implications for human health and disease. Nature Reviews Genetics 2015 Aug 18;16(9):530-42. doi: 10.1038/nrg3966. PMID:26281784

Taylor RW, Pyle A, Griffin H, Blakely EL, Duff J, He L, Smertenko T, Alston CL, Neeve VC, Best A, Yarham JW, Kirschner J, Schara U, Talim B, Topaloglu H, Baric I, Holinski-Feder E, Abicht A, Czermin B, Kleinle S, Morris AAM, Vassallo G, Gorman G, Ramesh V, Turnbull DM, Santibanez-Koref M, McFarland R, Horvath R, Chinnery PF. Use of whole exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiency. Journal of the American Medical Association 2014;312(1):68-77. PMID:25058219

Hudson G, Gomez-Duran A, Wilson IJ, Chinnery PF. Recent mitochondrial DNA mutations increase the risk of developing common late-onset human diseases. PLoS Genetics 2014:May 22;10(5):e1004369. doi: 10.1371/journal.pgen.1004369. eCollection 2014 May. PMID:24852434. Featured on http://blog.wellcome.ac.uk/2014/05/27/wellcome-trust-research-round-up-… and Nature Reviews Genetics 2014:15,440.

Pfeffer G, Gorman GS, Griffin H, Kurzawa-Akanbi  M, Blakely EL, Wilson I, Sitarz K, Moore D, Murphy JL, Alston CL, Pyle A, Coxhead J, Payne B, Gorrie GH, Longman C, Hadjivassiliou M, McConville J, Dick D, Imam I, Hilton D, Norwood F, Baker MR, Jaiser SR, Yu-Wai-Man P,  Farrell M, McCarthy A, Lynch T, McFarland R, Schaefer AM, Turnbull DM, Horvath ,Taylor RW, Chinnery PF. Mutations in the spastic paraplegia 7 gene (SPG7) cause chronic progressive external ophthalmoplegia through disordered mtDNA maintenance. Brain 2014 May;137(Pt 5):1323-36. PMID:24727571  PMCID: PMC3999722

Pfeffer P, Horvath R, Klopstock T, Mootha VK, Suomalainen A, Koene S, Hirano M, Zeviani M, Bindoff LA, Yu-Wai-Man P, Hanna M, Carelli V, McFarland R, Majamaa K, Turnbull DM, Smeitink J, Chinnery PF. New treatments for mitochondrial disease—no time to drop our standard. Nature Reviews Neurology 2013 Aug;9(8):474-81. PMID: 23817350

Freyer C, Cree LM, Mourier A, Stewart JB, Koolmeister C, Milenkovic D, Wai T, Floros V, Hagström E, Chatzidaki EE, Wiesner R, Samuels DC, Larsson N-G, Chinnery PF. Variation in germ line mtDNA heteroplasmy is determined prenatally but modified during subsequent transmission. Nature Genetics 2012;44(11):1282-5. PMID:23042113.

Pfeffer G, Griffin H, Pyle A, Horvath R, Chinnery PF. Hereditary myopathy with early respiratory failure is caused by mutations affecting the titin FN3 119 domain. Brain 2014 Apr;137(Pt 4):e271. PMID: 24271327  PMCID: PMC3959549

Payne BAI, Wilson IJ, Hateley CA, Horvath R, Santibanez-Koref M, Samuels DC, Price D Ashley, Chinnery PF. Mitochondrial aging is accelerated by anti-retroviral therapy through the clonal expansion of mtDNA mutations. Nature Genetics 2011:43(8):806-10. doi: 10.1038/ng.863. PMID:216060024.

Klopstock T, Yu-Wai-Man P, Dimitriadis K, Rouleau J, Heck S, Bailie M, Atawan A, Chattopadhyay S, Schubert M, Garip A, Kernt M, Petraki D, Rummey C, Leinonen M, Metz G, Griffiths PG, Meier T, and Chinnery PF. A randomized placebo-controlled trial of idebenone in Leber’s hereditary optic neuropathy. Brain 2011;134:2666-86. PMID: 21788663  PMCID: PMC3170530. Scientific commentary in Brain and New Scientist 30th July 2011, p11. Selected by the Faculty of 1000 to be on the top 2% of biology publications. 

Samuels DC,  Wonnapinij P, Cree LM, Chinnery PF. Reassessing evidence for a post-natal mitochondrial genetic bottleneck. Nature Genetics 2010: Jun;42(6):471-2. PMID: 20502486

Chinnery PF, Elliott HR, Syed A, Rothwell P Mitochondrial DNA sub-haplogroup K reduces the risk of transient ischaemic attack and ischaemic stroke. Lancet Neurology 2010 May;9(5):498-503. PMID: 20362514.

Cree LM, Samuels DC, Chuva de Sousa Lopes S, Rajasimha HK, Wonnapinij P, Mann JR, Dahl H-H.M. Chinnery PF. A reduction in the number of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes. Nature Genetics 2008: 40(2):249-54. PMID: 18223651

Baudouin SV, Saunders D, Tiangyou W, Elson J, Poynter J, Pyle A, Keers S, Turnbull DM, Howell N,

Chinnery PF. Mitochondrial DNA influences survival following sepsis: a prospective study. Lancet 2005;366:2118-2121. PMID:16360789

Chinnery PF Elliott HR, Patel S, Lambert C, Keers SM, Durham S, McCarthy M, Hitman GA, Hattersley AT, Walker M. Role of the mitochondrial DNA 16184-16193 poly-C tract in type 2 diabetes. Lancet 2005;366:1650-1651. PMID:16271646

Chinnery PF, DiMauro S, Shanske S, Schon EA, Zeviani M, Mariotti C, Carrara F, Lombes A, Laforet P, Ogier H, Jaksch M, Lochmüller H, Horvath R, Deschauer M, Thorburn DR, Bindoff LA, Poulton J, Taylor RW, Matthews JNS, Turnbull DM. The risk of developing a mitochondrial DNA deletion disorder. Lancet 2004:365:592-595. PMID:15313359