The Department of Pathology and Cell Biology at Columbia University Irving Medical Center seeks a highly qualified and motivated postdoctoral scientist to participate in NIH funded studies on the biology of essential tremor (ET) through study of human post-mortem brain specimens. The candidate will work with a collaborative team of researchers in Dr. Faust’s laboratory at Columbia University and will collaborate with Dr. Elan Louis at University of Texas Southwestern. The postdoc will participate in quantitative morphologic analyses in human brain tissue specimens and molecular analyses to map out biological changes in the tremor circuitry that may define disease pathogenesis in ET. The postdoc will utilize digital pathology programs and design machine learning programs to identify synaptic and other pathologic changes across brain regions. In a second project, we are exploring the role of dysregulated ER calcium handling in human ET brain samples and a novel mouse model with tremor using biochemical and morphologic techniques. No animal work is required, but analysis of mouse brain will be compared to human. We are looking for a self-starter with new ideas in the field of neurodegenerative pathology and a highly collaborative person who will bring energy to the lab group. The postdoc will also be involved in grant writing and submissions.
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- Analyze stained brain tissue sections with quantitative morphologic methods, including collecting microscopic images (light microscopy, confocal microscopy) and characterizing axonal and synaptic changes and other neuropathological parameters
- Analyze whole slide scanned digital images using digital image analysis programs
- Utilize machine learning to design quantitative digital image analyses
- Perform protein extractions and Western blot analyses of frozen brain tissues
- Participate in analysis of proteomics data and subsequent validation experiment
- Organization and interpretation of data from experiments
- Act as a resource for new team members and provide leadership to develop new protocols
- Participate in development of funding proposals and manuscripts
- Purchase necessary laboratory reagents and equipment
The laboratory of Dr. Phyllis Faust in the Department of Pathology and Cell Biology at Columbia University Medical Center investigates the pathogenesis of essential tremor (ET), a highly prevalent neurological disorder in which the underlying biology remains poorly understood. Our studies draw from the largest repository of autopsy brains from individuals with essential tremor through the Essential Tremor Centralized Brain repository at the NY Brain Bank. This is a joint effort between UT Southwestern and Columbia University investigators in a clinically well characterized, prospectively followed cohort of brain donors, providing a strong basis for determining clinical-pathological correlations.
We have identified degenerative changes in cerebellum as core biologic features in ET, supporting the hypothesis that the cerebellum and Purkinje cell dysfunction are central to tremor generation in ET. We developed a novel approach using statistical comparisons based on composite analyses of multiple quantitative morphological metrics to define disease patterns in cerebellar degenerations. We are currently mapping out the pathological changes in ET versus control autopsy brain specimens across cerebellar functional/anatomical compartments and correlating these changes with ET clinical phenotypes. We are also examining whether degenerative changes in ET may more broadly involve other structures in the cerebello-thalamo-cortical loop and olivo-cerebellar loop, as physiological networks posited to be involved in the origins and propagation of tremor in ET. Morphological studies will be combined with proteomic analyses in key regions of the tremor circuit in ET versus control brains to further identify molecular mechanisms of ET pathogenesis.
A second recently developed project will examine human brain tissues with Western blot analyses for molecules involved in calcium handling in endoplasmic reticulum, in cerebellum and other brain regions. In a novel mouse model with tremor, we will examine morphologic changes in the brain that occur with ER calcium dysregulation.