We propose to establish a National Research Resource for Imaging Mass Spectrometry at Vanderbilt University School of Medicine, Nashville, TN. The Resource would focus on technology advances and innovation that generally would include next generation hardware, software and methods relevant to direct tissue profiling and imaging using mass spectrometry. At the same time, a number of applications in the biological and medical area that would derive significant benefits from this developing technology will be undertaken. In turn, the technical needs of these biological investigations will feed back and help focus and drive additional technology improvement and innovation. The technology program proposed here would involve significant development of histology directed mass spectrometric profiling and imaging of tissues, a new ion source geometry for transmission geometry laser illumination of tissues for single cell analysis, high spatial resolution imaging down to one micron lateral resolution, high sensitivity profiling and imaging to measure lower abundance species than is now possible, and the development of the relevant bio-computational resources to complement the technological advances and enable it to be routinely used by biologists and medical research investigators who are not experts in the field of the technology. The driving biology would be focused on applications that would require new capabilities, such as high spatial resolution imaging of the serotonin neuron proteome in neuro-developmental disorders, studies of breast and prostate cancer, age related macular degeneration, selected stem cell analyses, studies of the glomerulus in diabetic nephropathy, molecular presentations in malformed heart valve development, and aspects of tumor angiogenesis and growth. Important activities of the Resource would also involve selected collaborations of NIH sponsored research that would significantly benefit from the developing technology of Imaging Mass Spectrometry, to offer core capabilities that include secondary ion mass spectrometry for ultra high resolution imaging of low MW species, and FT ICR instrumentation and expertise for ultra high mass spectrometric resolution Training and dissemination of the technology as well as the expertise present in the Resource would be accomplished through a yearly short course, individual scientific visits by established scientists and trainees, and publication of the outcomes of both the technology and applications programs.
The Resource is involved the discovery of molecular events that occur in disease using advanced instrumentation that is able to measure minute amounts of material. The Resource includes the development of 'next generation'technologies to make higher sensitivity and higher resolution measurements on tissues than can be done currently and apply these technologies to specific biological projects to study specific diseases, such as cancer, kidney disease, diabetes, and neurological disorders. The outcome of this work will be a new understanding of the biology of health and disease that will lead to new treatment opportunities for patients with these diseases.
| Grove, Kerri J; Lareau, Nichole M; Voziyan, Paul A et al. (2018) Imaging mass spectrometry reveals direct albumin fragmentation within the diabetic kidney. Kidney Int 94:292-302 |
| Angel, Peggi M; Baldwin, H Scott; Gottlieb Sen, Danielle et al. (2017) Advances in MALDI imaging mass spectrometry of proteins in cardiac tissue, including the heart valve. Biochim Biophys Acta Proteins Proteom 1865:927-935 |
| Bloom, Anna N; Tian, Hua; Winograd, Nicholas (2015) C60-SIMS imaging of nanoparticles within mammalian cells. Biointerphases 11:02A306 |
| Floyd, Kyle A; Moore, Jessica L; Eberly, Allison R et al. (2015) Adhesive fiber stratification in uropathogenic Escherichia coli biofilms unveils oxygen-mediated control of type 1 pili. PLoS Pathog 11:e1004697 |
| Winograd, Nicholas; Bloom, Anna (2015) Sample preparation for 3D SIMS chemical imaging of cells. Methods Mol Biol 1203:9-19 |
| Anderson, David M G; Ablonczy, Zsolt; Koutalos, Yiannis et al. (2014) High resolution MALDI imaging mass spectrometry of retinal tissue lipids. J Am Soc Mass Spectrom 25:1394-403 |
| Schmidt, M J; Horvath, S; Ebert, P et al. (2014) Modulation of behavioral networks by selective interneuronal inactivation. Mol Psychiatry 19:580-7 |
| Libes, Jaime M; Seeley, Erin H; Li, Ming et al. (2014) Race disparities in peptide profiles of North American and Kenyan Wilms tumor specimens. J Am Coll Surg 218:707-20 |
| Lerach, Jordan O; Keskin, Selda; Winograd, Nicholas (2014) Investigations Into the Interactions of a MALDI Matrix with Organic Thin Films Using C60 (+) SIMS Depth Profiling. Surf Interface Anal 46:67-69 |
| Grove, Kerri J; Voziyan, Paul A; Spraggins, Jeffrey M et al. (2014) Diabetic nephropathy induces alterations in the glomerular and tubule lipid profiles. J Lipid Res 55:1375-85 |
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