My lab studies mechanisms of neurodegeneration: several projects are ongoing - (1) animal models of Parkinson’s disease (PD) are used to gain insight into the cause of the disease, and to evaluate novel treatments to slow/stop the neurodegenerative process. Current studies involve the development of a rat model of PD; (2) proteomic techniques are being used to develop a blood test for PD and Alzheimer’s disease (AD). Blood from patients with the two diseases, and from normal control subjects, are examined using novel and highly sensitive mass spectroscopy techniques, in order to identify unique sets of proteins/peptides that are characteristic of the diseases. Such markers will be useful for early disease diagnosis, before significant neurodegeneration has occurred; (3)sensitive GCMS techniques have been used to find that blood from PD patients contain 10-fold higher levels of a pesticide compared to normal controls and those with AD. We are testing whether these high levels are due to polymorphisms in genes that metabolism the organochloride compounds. These studies may lead to the development of tests for the early detection of PD and ways to stop the disease progression;(4) we have found that the thalamus is enlarged in post-mortem brains from patients with major depressive disorder (MDD), and that the enlargement is correlated with the individuals carring a serotonin transporter gene polymorphism that has been shown previously to play a role in MDD. We are currently studying whether this serotonin polymorphism contributes to the enlargement of the thalamus using a mouse with this gene knocked out.
RESEARCH INTERESTS
My lab focuses on the cellular and molecular mechanisms responsible for neurodegenerative and psychiatric diseases.
Human post-mortem tissue and animal models of both Parkinson’s disease and Alzheimer’s disease are studied to understand the mechanisms responsible for selective vulnerability of specific populations of neurons. The animal models are also used to study potential therapies.
Post-mortem tissues from individuals with affective disorder are used to identify cellular and molecular alterations to provide insight into the etiology of the disorders.
RECENT PUBLICATIONS
Yazdani U, German DC, Manzino L, Sonsalla PK, Zeevalk GD., "Rat model of Parkinson’s disease: chronic central delivery of MPP+" Exp. Neurol., 200:172-183, 2006
Young KA, Holcomb LA, Bonkale WL, Hicks PB, Yazdani U, German DC., "5HTTLPR polymorphism and enlargement of the pulvinar: unlocking the backdoor to the limbic system." Biol. Psychiat., 61:813-818, 2007
German DC, Gurnani P, Nandi A, Garner HR, Fisher W, Diaz-Arrastia R, O’Suilleabhain P, Rosenblatt KP., "Serum biomarkers for Alzheimer’s disease: proteomic discovery." Biomedicine & Pharmacotherapy, Jun 18; [Epub] 2007
Fisher WG, Rosenblatt KP, Fishman DA, Whiteley GR, Mikulskis A, Kuzdzal SA, Lopez MF, Tan NC., German DC, Garner HR., "A robust biomarker discovery pipeline for high performance mass spectrometry data." Bioinformatics and Computat. Biol., in press 2007
DC German, "Mouse models of Alzheimer’s disease." In - A-beta peptide and Alzheimer’s disease. C. J. Barrow and D. H. Small, eds. Springer Verlag, London., Chapter 16, 2007
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