Our laboratory has recently described a novel pathway whereby α-synuclein, a protein linked to Parkinson’s disease, can cause the hyperphosphorylation of Tau [p-Tau], a protein linked to Alzheimer’s disease, thereby implicating p-Tau in the genesis of PD and α-Syn in the genesis of AD. This pathway has been confirmed in MPTP animal models of PD as well as in human post-mortem tissues. Published studies can be found in PubMed.
We would now like to understand the mechanism by which environmental toxins induce neurodegenerative changes leading to synucleopathies and tauopathies in cell and animal models; to develop biomarkers for early identification of these diseases and to develop novel treatment strategies for the prevention of neurodegeneration. Wild type and transgenic mice overexpressing α-synuclein will be treated with rotenone or MPTP, and changes in α-synuclein, p-Tau [phosphorylated at different sites identified by Western blots and proteomics], and associated kinases and phosphatases will be identified. Immunohistochemistry will be used to confirm neurodegeneration. MRI and MRS will be used to measure changes in vivo, enabling us to longitudinally follow disease progression within the same animal, particularly during the early stages of neurodegeneration, for developing possible biomarkers in humans. We will explore several neuroprotective strategies to prevent or reduce the severity of neurodegenerative changes. We will test a novel groups inhibitor in preventing activation of Tau-specific kinases. We will also test the neuroprotective effect of parkin, through lentiviral delivery in specific brain regions, to examine accelerated clearance of aggregates of α-synuclein and p-Tau via proteosomes.
Specific Requirements for Fellows
A strong background and interest in neurodegenerative diseases or neuroscience, as evidenced by publications is mandatory. Prior experience in two or more of the following techniques is also desirable: signal transduction, study of kinases, immunohistochemistry, whole animal studies and stereotaxic surgery, molecular and neurochemical techniques, MRI or MRS experience.
Research Project of the desired postdoctoral fellow
Will depend on the past research experience of the fellow, but will involve one or more of the above listed projects ongoing in the laboratory.
Applications for 2008-09 Fellowships
Contact Information
Anita Sidhu, Ph.D., Professor and Head of Laboratory of Molecular Neurochemistry, Department of Biochemistry and Molecular and Cell Biology, sidhua@georgetown.edu
- Chemical and Process Engineering PhD Scholarship, University of Canterbury September 25th, 2011
- International Student Scholarships in Science at University of Hull, UK June 6th, 2011
- PhD Studentship in Chemistry for International Students, Poland March 9th, 2011
- Post-doctoral position in Biochemistry/Molecular biology October 31st, 2010
- Post Doctoral Fellow-Radiology Thomas Jefferson University, USA October 24th, 2010
- January 8th
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