I'm interested in understanding the impact of mitochondrial DNA mutations on the brain and how they contribute to development of neurological deficits, such as ataxia and epilepsy, in patients with mitochondrial disease. One of my current studies is focussed on elucidating the pathological mechanisms responsible for grey matter cortical lesions commonly reported in patients. I want to understand the symptoms associated with these features, such as epilepsy and stroke-like episodes, and how they impact on disease progression. The majority of my work uses human brain tissue to characterise and investigate pathological changes using a combination of molecular genetics, enzyme histochemistry and immunohistochemistry. To help me with my research I collaborate with a diverse range of people from different specialities including, neurologists, electrophysiologists, neuroradiologists, neuropathologists, staff at the NBTR and other members of within our group. In the future I hope to be able to investigate the observed neuropathological changes using appropriate animal models.

• Ng YS, Lax NZ, Maddison P, Alston CL, Blakely EL, Hepplewhite PD, Riordan G, Meldau S, Chinnery PF, Pierre G, Chronopoulou E, Du A, Hughes I, Morris AA, Kamakari S, Chrousos G, Rodenburg RJ, Saris CGJ, Feeney C, Hardy SA, Sakakibara T, Sudo A, Okazaki Y, Murayama K, Mundy H, Hanna MG, Ohtake A, Schaefer AM, Champion MP, Turnbull DM, Taylor RW, Pitceathly RDS, McFarland R, Gorman GS. MT-ND5 Mutation Exhibits Highly Variable Neurological Manifestations at Low Mutant Load. EBioMedicine 2018, 30, 86-93.
• Lax NZ, Gorman GS, Turnbull DM. Central nervous system involvement in mitochondrial disease. Neuropathology and Applied Neurobiology 2017, 43(2), 102-118.
• Alston CL, Rocha MC, Lax NZ, Turnbull DM, Taylor RW. The genetics and pathology of mitochondrial disease. Journal of Pathology 2017, 241(2), 236-250.
• Khundakar AA, Hanson PS, Erskine D, Lax NZ, Roscamp J, Karyka E, Tsefou E, Singh P, Cockell SJ, Gribben A, Ramsay L, Blain PJ, Mosimann UP, Lett DJ, Elstner M, Turnbull DM, Xiang CC, Brownstein MJ, O'Brien JT, Taylor JP, Attems J, Thomas AJ, McKeith IG, Morris CM. Analysis of primary visual cortex in dementia with Lewy bodies indicates GABAergic involvement associated with recurrent complex visual hallucinations. Acta Neuropathologica Communications 2016, 4, 66.
• Phillips J, Laude A, Lightowlers R, Morris CM, Turnbull DM, Lax NZ. Development of passive CLARITY and immunofluorescent labelling of multiple proteins in human cerebellum: understanding mechanisms of neurodegeneration in mitochondrial disease. Scientific Reports 2016, 6, 26013.
• Lax NZ, Grady J, Laude A, Chan F, Hepplewhite PD, Gorman G, Whittaker RG, Ng Y, Cunningham MO, Turnbull DM. Extensive respiratory chain defects in inhibitory interneurones in patients with mitochondrial disease. Neuropathology and Applied Neurobiology 2016, 42(2), 180-193.
• Phillips J, Hayhurst H, Lax NZ. Neurodegeneration in mitochondrial disorders. In: Reeve A; Simcox E; Duchen M; Turnbull D, ed. Mitochondrial Dysfunction in Neurodegenerative Disorders: Second Edition. Cham: Springer International Publishing, 2016, pp.33-58.
• Chan F, Lax NZ, Davies CH, Turnbull DM, Cunningham MO. Neuronal oscillations: a physiological correlate for targeting mitochondrial dysfunction in neurodegenerative diseases?. Neuropharmacology 2016, 102, 48-58.
• Ng YS, Grady JP, Lax NZ, Bourke JP, Alston CL, Hardy SA, Falkous G, Schaefer AG, Radunovic A, Mohiddin SA, Ralph M, Alhakim A, Taylor RW, McFarland R, Turnbull DM, Gorman GS. Sudden adult death syndrome in m.3243A>G-related mitochondrial disease: an unrecognized clinical entity in young, asymptomatic adults. European Heart Journal 2016, 37(32), 2552-2559.
• Whittaker RG, Devine HE, Gorman GS, Schaefer AM, Horvath R, Ng Y, Nesbitt V, Lax NZ, McFarland R, Cunningham MO, Taylor RW, Turnbull DM. Epilepsy in Adults With Mitochondrial Disease: A Cohort Study. Annals of Neurology 2015, 78(6), 949-957.
• Chrysostomou A, Grady JP, Laude A, Taylor RW, Turnbull DM, Lax NZ. Investigating complex I deficiency in Purkinje cells and synapses in patients with mitochondrial disease. Neuropathology and Applied Neurobiology 2016, 42(5), 477-492.
• Lax NZ, Alston CL, Schon K, Park S, Krishnakumar D, He L, Falkous G, Ogilvy-Stuart A, Lees C, King RH, Hargreaves IP, Brown GK, McFarland R, Dean AF, Taylor RW. Neuropathologic Characterization of Pontocerebellar Hypoplasia Type 6 Associated With Cardiomyopathy and Hydrops Fetalis and Severe Multisystem Respiratory Chain Deficiency due to Novel RARS2 Mutations. Journal of Neuropathology & Experimental Neurology 2015, 74(7), 688-703.
• Grünewald A, Lax NZ, Rocha MC, Reeve AK, Hepplewhite PD, Rygiel KA, Taylor RW, Turnbull DM. Quantitative quadruple-label immunofluorescence of mitochondrial and cytoplasmic proteins in single neurons from human midbrain tissue. Journal of Neuroscience Methods 2014, 232, 143-149.
• Ng YS, Lax N, Schaefer A, Radunovic A, Ralph M, Alhakim A, Taylor R, Turnbull D, McFarland R, Gorman G. Sudden Unexpected Death in Adults with M.3243A>G Mutation. In: Association of British Neurologists Annual Meeting. 2014, Cardiff, UK: BMJ Publishing Group.
• Lax NZ, Gnanapavan S, Dowson SJ, Alston CL, He LP, Polvikoski TM, Jaros E, O'Donovan DG, Yarham JW, Turnbull DM, Dean AF, Taylor RW. Early-Onset Cataracts, Spastic Paraparesis, and Ataxia Caused by a Novel Mitochondrial tRNA(Glu) (MT-TE) Gene Mutation Causing Severe Complex I Deficiency: A Clinical, Molecular, and Neuropathologic Study. Journal of Neuropathology and Experimental Neurology 2013, 72(2), 164-175.
• Bogle H, Lax NZ, Jaros E, McFarland R, Taylor RW, Turnbull DM. Neuropathological changes in Alpers' syndrome. In: 114th Meeting of the British Neuropathological Society: Symposium on Advances in Motor Neuron Diseases. 2013, London: Wiley-Blackwell Publishing Ltd.
• Reeve A, Meagher M, Lax N, Simcox E, Hepplewhite P, Jaros E, Turnbull D. The Impact of Pathogenic Mitochondrial DNA Mutations on Substantia Nigra Neurons. Journal of Neuroscience 2013, 33(26), 10790-10801.
• Lax NZ, Hepplewhite PD, Reeve AK, Nesbitt V, McFarland R, Jaros E, Taylor RW, Turnbull DM. Cerebellar Ataxia in Patients With Mitochondrial DNA Disease: A Molecular Clinicopathological Study. Journal of Neuropathology and Experimental Neurology 2012, 71(2), 148-161.
• Lax NZ, Campbell GR, Reeve AK, Ohno N, Zambonin J, Blakely EL, Taylor RW, Bonilla E, Tanji K, DiMauro S, Jaros E, Lassmann H, Turnbull DM, Mahad DJ. Loss of Myelin-Associated Glycoprotein in Kearns-Sayre Syndrome. Archives of Neurology 2012, 69(4), 490-499.
• Lax NZ, Pienaar IS, Reeve AK, Hepplewhite PD, Jaros E, Taylor RW, Kalaria RN, Turnbull DM. Microangiopathy in the cerebellum of patients with mitochondrial DNA disease. Brain 2012, 135(6), 1736-1750.
• Picard DM, Lax N, Ratnaike T, Juster RP, Turnbull DM. Mitochondrial allostatic load? The combined effect of glucose intolerance and mitochondrial DNA mutations on the incidence of neurological symptoms. In: 42nd Annual Conference on Effects of Traumatic Stress. 2012, New York, NY, USA: Co-Action Publishing.
• Lax NZ, Jaros E. Neurodegeneration in primary mitochondrial disorders. In: Reeve, A.K., Krishnan, K.J., Duchen, M.R., Turnbull, D.M, ed. Mitochondrial Dysfunction in Neurodegenerative Disorders. Berlin; New York: Springer, 2012, pp.21-42.
• Reeve AK, Park TK, Jaros E, Campbell GR, Lax NZ, Hepplewhite PD, Krishnan KJ, Elson JL, Morris CM, McKeith IG, Turnbull DM. Relationship Between Mitochondria and α-Synuclein: A Study of Single Substantia Nigra Neurons. Archives of Neurology 2012, 69(3), 385-393.
• Lax NZ, Whittaker RG, Hepplewhite PD, Reeve AK, Blakely EL, Jaros E, Ince PG, Taylor RW, Fawcett PR, Turnbull DM. Sensory neuronopathy in patients harbouring recessive polymerase γ mutations. Brain 2012, 135(1), 62-71.
• Lax NZ, Turnbull DM, Reeve AK. Mitochondrial mutations: newly discovered players in neuronal degeneration. Neuroscientist 2011, 17(6), 645-648.