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Senior Investigator

Mark R. Cookson, Ph.D.

NIA
Building 35 Room 1A116
35 Convent Drive MSC3707
Bethesda MD 20892-3707
Office: (301) 451-3870

Fax: (301) 451-7295
Cookson@mail.nih.gov

Dr. Cookson received both his B.Sc. and Ph.D. degrees from the University of Salford, UK, in 1991 and 1995, respectively. He obtained postdoctoral training at the Medical Research Council laboratories and the University of Newcastle, UK, before joining the Mayo Clinic in Jacksonville, Florida, as a Senior Research Fellow and Assistant Professor of Neuroscience. Dr. Cookson moved to the NIA in 2002 and is currently and Investigator in the Laboratory of Neurogenetics. His group uses cellular and molecular biology tools to study inherited neurodegenerative disorders such as Parkinson's disease, attempting to understand the mechanisms leading to neuronal damage.



(1) Modeling effects of mutations associated with familial neurodegeneration in vitro (2) Neuronal phenotype and selective vulnerability in Parkinson's disease (3) Contribution of glial cells to neurological disease and neurotoxicity.

My research has focused on the cell biology of the nervous system, as applied to the study of neurotoxic agents (PhD thesis work) and subsequently applied to the study of human neurological disorders. During my postdoctoral work, I developed a strong interest in the application of genetic information to the understanding of human diseases, first in amyotrophic lateral sclerosis and subsequently in Parkinson's disease. With respect to Parkinson's disease, I am particularly interested in the relationships between recessive gene products and the toxic effects of aggregating proteins that are produced by dominant gene mutations. Whilst at the Mayo clinic, Jacksonville, I received RO1 funding from NIH to work parkin and alpha-synuclein in relation to familial Parkinson's disease.

One problem that particularly intrigues me is the phenomenon of selective vulnerability in these disorders where different neuronal groups are affected. In Parkinson's disease, for example, we have examined the vulnerability of different neuronal groups to alpha-synuclein mediated cellular damage. This approach of combining genetic information with cellular models has yielded a number of high profile publications in the last two years (see bibliography). I am currently running an eight-person group at NIH in the laboratory of Neurogenetics, NIA. More information about my research can be found at: http://www.grc.nia.nih.gov/branches/lng/cbgeu.htm.




Dynamic aggregation processes of alpha-synuclein 

Dynamic aggregation processes of alpha-synuclein.

Dynamic aggregation processes of alpha-synuclein. Like other labs, we have found that the small synaptic protein alpha-synuclein, can aggregate and is associated with damage to neurons. This figure indicates that alpha-synuclein normally exists in equilibrium between membranes and the cytosol. Structurally, alpha-synuclein is unfolded in solution (indicated by the extended bar) but forms helix-like strcutures in association with membranes (top). In pathological conditions, including Parkinson disease, alpha-synuclein aggregates via small oligomeric intermediates to larger fibrillar forms as indicated by the progression down the figure, eventually being deposited into pathological structures known as Lewy bodies. There are several mutations in the gene associated with Lewy body diseases and their effects on promoting aggregation are indicated by arrows.

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