I’m a Research Associate in the Wellcome Trust Centre for Mitochondrial Research where I have a major interest in understanding neurological impairments in patients with mitochondrial disease. Over the last 4 years, I have been fortunate to work under the guidance of Professors Rob Taylor and Doug Turnbull in a stimulating research environment with excellent clinical and scientific streams of research.
My post-doctoral research builds upon the research completed during my PhD and focuses on addressing the mechanisms by which mitochondrial DNA mutations affect the brain and cause neurological conditions including epilepsy, dementia and ataxia. 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.
Neurological deficits are frequently seen in patients with mitochondrial disease and can be incredibly debilitating so by doing this type of research we can begin to understand disease progression and develop new therapeutic strategies to improve patient care and quality of life. This is what motivates me as a scientist.
Principal Investigators: Professor Doug Turnbull and Professor Rob Taylor
Other staff members involved: Philippa Hepplewhite
Neurological deficits in patients with mitochondrial DNA (mtDNA) disease are frequent and often the most debilitating part of the disease. We have a strong interest in understanding molecular mechanisms resulting in mitochondrial dysfunction and the impact of this on neurons and other cells types in the CNS of patients with mtDNA disease. Using our unique post mortem human brain tissue collection from the Newcastle Brain Tissue Resource, we are able to perform in-depth analysis of brain tissue from patients with mtDNA disease due to a number of different genetic defects. We employ immunohistochemical, histochemical, biochemical, and molecular genetic techniques to elucidate neuropathological changes occurring due to mtDNA disease.
Our current studies aim to better understand neurological deficits, such as epilepsy, stroke-like episodes and ataxia in patients, by characterising the level of mitochondrial impairment and the impact on neural function.
Sponsor/Funder: Wellcome Trust
Collaborators: Newcastle Brain Tissue Resource
External Links: http://www.ncl.ac.uk/iah/about/facilities/nbtr/index.htm
1. Book chapter: Mitochondrial Disorders. Greenfield’s Neuropathology – Ninth edition. Chinnery PF, Lax NZ, Jaros E, Taylor RW, Turnbull DM, DiMauro S. In press.
2. Microangiopathy in the cerebellum of patients with mitochondrial DNA disease. Lax NZ, Pienaar IS, Reeve AK, Hepplewhite PD, Jaros E, Taylor RW, Kalaria RN, Turnbull DM. Brain. 2012 Jun;135(Pt 6):1736-50.
3. Loss of myelin-associated glycoprotein in kearns-sayre syndrome. 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. Arch Neurol. 2012 Apr;69(4):490-9.
4. Book Chapter: Neurodegeneration in Primary Mitochondrial Disorders. Mitochondrial Dysfunction in Neurodegenerative Disorders. Lax NZ, Jaros E. 2012.
5. Relationship between mitochondria and α-synuclein: a study of single substantia nigra neurons. Reeve AK, Park TK, Jaros E, Campbell GR, Lax NZ, Hepplewhite PD, Krishnan KJ, Elson JL, Morris CM, McKeith IG, Turnbull DM. Arch Neurol. 2012 Mar;69(3):385-93.
6. Cerebellar ataxia in patients with mitochondrial DNA disease: a molecular clinicopathological study. Lax NZ, Hepplewhite PD, Reeve AK, Nesbitt V, McFarland R, Jaros E, Taylor RW, Turnbull DM. J Neuropathol Exp Neurol. 2012 Feb;71(2):148-61.
7. Sensory neuronopathy in patients harbouring recessive polymerase γ mutations. Lax NZ, Whittaker RG, Hepplewhite PD, Reeve AK, Blakely EL, Jaros E, Ince PG, Taylor RW, Fawcett PR, Turnbull DM. Brain. 2012 Jan;135(Pt 1):62-71. Epub 2011 Dec 20.
8. Mitochondrial DNA Mutations: Newly Discovered Players in Neuronal Degeneration. Lax NZ, Turnbull DM, Reeve AK. Neuroscientist. In press.
9. The mitochondrial brain: From mitochondrial genome to neurodegeneration. Turnbull HE, Lax NZ, Diodato D, Ansorge O, Turnbull DM. Biochim Biophys Acta. 2010 Jan;1802(1):111-21.
10. Mitochondrial changes within axons in multiple sclerosis. Mahad DJ, Ziabreva I, Campbell G, Lax N, White K, Hanson PS, Lassmann H, Turnbull DM. Brain. 2009 May;132(Pt 5):1161-74.