Keynote Speaker: Richard Caprioli Vanderbilt University, Nashville In situ molecular imaging and profiling of proteins in tissues using mass spectrometry in biological and clinical research Profiling and Imaging MALDI MS can be used to assess the spatial distribution of peptides and proteins in biological samples, and is especially effective in its application to tissue sections. Applications range from low-resolution images of peptides and proteins in selected areas of tissue to high resolution images of tissue cross sections. Using a raster of the tissue surface by a laser beam, images of samples are produced in specific m/z values, or ranges of values. Each spot on the sample irradiated by the laser is approximately 30-50 microns in diameter and typically covers the m/z range 1000-100,000. Individual m/z values can then be assembled from the mass spectra to produce selected m/z images. Sections obtained from any tissue type can be imaged to locate tissue specific peptides and proteins in X, Y coordinates of the tissue. We have employed the technology in studies of a variety of diseases, including several types of cancers, neurodegenerative diseases and kidney diseases, comparing proteins differentially expressed in diseased tissue with those in the corresponding normal tissue. This will be illustrated with studies of breast tumor biopsies and also those for human glioblastomas. In the latter, MS patterns have also been correlated with patient outcomes. This has been applied to a protocol termed histology-directed molecular analysis of tissue and biopsy specimens. Imaging MS has also been applied to drug targeting and metabolic studies with analysis of specific tissues after systemic drug administration. Whole animal sagittal sections have been imaged to measure molecular changes in proteins in multiple organs and correlating this with drug concentrations in these same organs.