Timothy Garrett (Presenter)
University of Florida
Bio: I received my undergraduate degree from the University of Georgia in Chemistry. As an undergraduate, I worked in the lab of Dr. I. Jonathan Amster on the characterization of bacterial proteins using MALDI-TOF completing an undergraduate thesis. After taking 2 years off, I enrolled in the PhD program at the University of Florida working under the direction of Dr. Richard A. Yost. As a graduate student, I developed the first imaging mass spectrometry based on ion trap instrumentation through a partnership with Thermo and studied the disposition of phospholipids in brain tissue. After graduating, I took over a mass spectrometry facility in the college of medicine transforming it into a targeted quantitation and global profiling metabolomic lab. I am currently the Director of Core 1, high throughput metabolomics, for the Southeast Center for Integrated Metabolomics and an assistant prof
Authorship: Timothy J. Garrett, PhD(1), Emily Gill(2), Vinata Vedam-Mai, PhD(3), and Michael S. Okun, MD(4)
(1)Department of Pathology, Immunology and Laboratory Medicine (2) Department of Chemistry (3) Department of Neurosurgery (4) Department of Neurology
Imaging mass spectrometry (IMS) enables the direct analysis of compounds from tissue and the technique produces images that correlate to the distribution in tissue. When connected to metabolomics, this technique can provide a unique perspective of metabolism. Parkinson’s Disease (PD) is a movement disorder involving the loss of dopaminergic neurons as well as degeneration of multiple brain circuits. Deep brain stimulation (DBS) is a surgical treatment utilizing electrical stimulation to target a specific brain nucleus. Despite the effectiveness of DBS, little is known about the mechanism. We have utilized IMS and LC-HRMS metabolomics to evaluate the changes in small molecules in relation to PD and the potential changes to small molecules following DBS.
Imaging mass spectrometry (IMS) enables the direct analysis of compounds from tissue producing images that correlate to the distribution of each individual compound. Metabolomics is a powerful analytical approach that measures the numerous small molecules present in our bodies that can represent the direct assessment of a disease phenotype. When IMS is connected to metabolomics, it can provide a unique perspective of tissue metabolism. Parkinson’s Disease (PD) is a movement disorder involving the loss of dopaminergic neurons reducing the production of dopamine, and there is also degeneration of multiple neural circuits. Deep brain stimulation (DBS) is a surgical treatment utilizing chronic electrical stimulation to treat PD. Despite the effectiveness of DBS, little is known about its mechanism of action. We have utilized IMS and LC-HRMS metabolomics to evaluate the changes in small molecules in relation to PD and the potential changes to small molecules following DBS. One challenge in comparing brains from different animal models of disease is sectioning at the same location, which is critical for PD studies. We will present initial data using brain blocks that enabled improved sectioning, and a better representation of different regions of the mouse brain; and therefore improved characterization of tissues between different animals. We will also present data from two different IMS approaches, matrix-assisted laser desorption ionization (MALDI) and desorption electrospray ionization (DESI), as they relate to small molecule imaging in PD. We have found that these techniques are often complementary, thus improving the overall understanding of the distribution of small molecules. In our experience, intermediate pressure MALDI provides better spatial resolution at the cost of more complex sample preparation while DESI enables more rapid, less spatially resolved images at the cost of a potential for rapid changes to metabolites during analysis, since it occurs at atmospheric pressure.
In addition to the animal model, we also analyzed postmortem tissue for small molecule changes from around the DBS lead of a PD-DBS patient. In this experiment, small pieces of tissue were removed from the brain along a linear plane and then subjected to LC-HRMS global metabolomic profiling. Using multivariate techniques, a number of unique small molecule metabolites were identified. We will share the initial results from this experiment and the potential of these approaches in postmortem tissue analysis.
References & Acknowledgements:
The authors acknowledge the support of NIH (Southeast Center for Integrated Metabolomics, U24 DK097209.
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