I am a Parkinson’s UK Research Fellow. I perform my own research and supervise students within the lab. I work with Prof. Doug Turnbull who is my supervisor, in addition I work closely with Eve Simcox and Dr. Nichola Lax.
I am motivated to pursue my research interest in mitochondria because I know that the key to understanding what causes Parkinson’s disease lies within the biology of these organelles. I also think that any future hope for new therapeutic interventions will come from understanding the role that mitochondria play in this disease.
Principal Investigator: Dr Amy Reeve
Other staff members involved: Eve Simcox
I am interested in understanding how mitochondrial dysfunction contributes to the loss of neurons within the substantia nigra. This death of brain cells causes Parkinson’s disease, which affects over 100,000 people within the UK.
I am primarily interested in finding out how mitochondrial dysfunction might lead to this loss of neurons and why these cells seem to be particularly sensitive to mitochondrial defects. Mitochondrial dysfunction will lead to the dysregulation of a number of neuronal processes including calcium handling, synaptic transmission and protein degradation. I am investigating how all these processes interact to cause the loss of cells in this brain region.
Sponsor/Funder: Medical Research Council and The Centre for Brain Ageing and Vitality
Collaborators: Prof J. Surmeier, Northwestern University Chicago
1. Campbell GR, Kraytsberg Y, Krishnan KJ, Ohno N, Ziabreva I, Reeve A, Trapp BD, Newcombe J, Reynolds R, Lassmann H, Khrapko K, Turnbull DM, Mahad DJ. Clonally expanded mitochondrial DNA deletions within the choroid plexus in multiple sclerosis. Acta Neuropathol. 2012 Jun 12. [Epub ahead of print].
2. Campbell GR, Reeve A, Ziabreva I, Polvikoski TM, Taylor RW, Reynolds R, Turnbull DM, Mahad DJ. Mitochondrial DNA deletions and depletion within paraspinal muscles.Neuropathol Appl Neurobiol. 2012. [Epub ahead of print]
3. 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 May 9. [Epub ahead of print]
4. 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. Arch Neurol. 2012 Apr;69(4):490-9.
5. Reeve AK, Park TK, Jaros E, Campbell GR, Lax NZ, Hepplewhite PD, Krishnan KJ, Elson JL, Morris CM, McKeith IG, Turnbull DM. The relationship between mitochondria and α-synuclein – A study of single substantia nigra neurons. Archives of neurology. 2012 69(3):385-93
6. 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. J Neuropathol Exp Neurol. 2012 Feb;71(2):148-161.
7. 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. 2011 Dec 20. [Epub ahead of print]
8. Greaves LC, Reeve AK, Taylor RW, Turnbull DM. Mitochondrial DNA and disease. J Pathol. 2011 Oct 12. 226(2):274-86
9. Lax NZ, Turnbull DM, Reeve AK. Mitochondrial Mutations: Newly Discovered Players in Neuronal Degeneration.. Neuroscientist. 2011 Mar 30. [Epub ahead of print]
10. Campbell GR, Ziabreva I, Reeve AK, Krishnan KJ, Reynolds R, Howell O, Lassmann H, Turnbull DM, Mahad DJ. Mitochondrial DNA deletions and neurodegeneration in multiple sclerosis. Ann Neurol. 2011 Mar;69(3):481-92.
11. Yu-Wai-Man P, Sitarz KS, Samuels DC, Griffiths PG, Reeve AK, Bindoff LA, Horvath R, Chinnery PF. OPA1 mutations cause cytochrome c oxidase deficiency due to loss of wild-type mtDNA molecules. Hum Mol Genet. 2010 May 18.
12. Krishnan KJ, Blackwood JK, Reeve AK, Turnbull DM, Taylor RW. Detection of mitochondrial DNA variation in human cells. Methods Mol Biol. 2010;628:227-57.
13. Mahad DJ, Ziabreva I, Campbell G, Laulund F, Murphy JL, Reeve AK, Greaves L, Smith KJ, Turnbull DM. Detection of cytochrome c oxidase activity and mitochondrial proteins in single cells. J Neurosci Methods. 2009 Aug 30.
14. Reeve AK, Krishnan KJ, Taylor G, Elson JL, Bender A, Taylor RW, Morris CM, Turnbull DM. The low abundance of clonally expanded mitochondrial DNA point mutations in aged substantia nigra neurons. Aging Cell. 2009 Aug;8(4):496-8. Epub 2009 May 31.
15. Betts-Henderson J, Jaros E, Krishnan KJ, Perry RH, Reeve AK, Schaefer AM, Taylor RW, Turnbull DM. Alpha-synuclein pathology and Parkinsonism associated with POLG1 mutations and multiple mitochondrial DNA deletions. Neuropathology and Applied Neurobiology. 2009 Feb;35(1):120-4.
16. Reeve AK, Krishnan KJ, Turnbull DM. Mitochondrial DNA mutations in Disease, Aging and Neurodegeneration. Annals of the New York Academy of Sciences. 2008.1147:21-29.
17. Reeve AK, Krishnan KJ, Turnbull DM. Age related mitochondrial degenerative disorders in humans. Biotechnology Journal. 2008 Jun;3(6):750-6.
18. Hu NJ, Yusof AM, Winter A, Osman A, Reeve AK, Hofmann A. The crystal structure of calcium-bound annexin Gh1 from Gossypium hirsutum and its implications for membrane binding mechanisms of plant annexins. Journal of Biological Chemistry. 2008 Jun 27;283(26):18314-22.
19. Krishnan KJ, Reeve AK, Samuels DC, Chinnery PF, Blackwood JK, Taylor RW, Wanrooij S, Spelbrink JN, Lightowlers RN, Turnbull DM.What causes mitochondrial DNA deletions in human cells? Nature Genetics. 2008 Mar;40(3):275-9.
20. Reeve AK, Krishnan KJ, Elson JL, Morris CM, Bender A, Lightowlers RN, Turnbull DM. Nature of mitochondrial DNA deletions in substantia nigra neurons. American Journal of Human Genetics. 2008 Jan;82(1):228-35.
21. Krishnan KJ, Reeve AK, Turnbull DM. Do mitochondrial DNA mutations have a role in neurodegenerative disease? Biochemical Society Transactions. 2007 Nov; 35(Pt 5):1232-5.
22. Krishnan KJ, Greaves LC, Reeve AK, Turnbull DM. The ageing mitochondrial genome. Nucleic Acids Research. 2007;35(22):7399-405.
23. Krishnan KJ, Greaves LC, Reeve AK, Turnbull DM. Mitochondrial DNA mutations and aging. Annals of the New York Academy of Sciences. 2007 Apr;1100:227-40.
24. Bender A, Krishnan KJ, Morris CM, Taylor GA, Reeve AK, Perry RH, Jaros E, Hersheson JS, Betts J, Klopstock T, Taylor RW, Turnbull DM. High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nature Genetics. 2006 May;38(5):515-7.