The laboratory focus is direct identification and quantification of peptide and protein biomarkers from tissues and body fluids. Biomarkers are diagnostic, staging, prognostic, and clinical response tools. Their greatest value is in "proof of concept" efficiency and safety evaluations of in vitro and in vivo studies in animal models or early phase clinical trials. The laboratory uses matrix-assisted laser desorption ionization, MALDI, Shimadzu Axima TOF2, nanoflow liquid chromatography electrospray mass spectrometry, Hitachi NanoFrontier LCMS, and Fourier transform mass spectrometry, FTMS, Bruker 12 Tesla, to identify femptomolar quantities of proteins such as hCG, in in-vitro fertilization embryo growth media and colon cancer; and histone and beta-tubulin directly from breast cancer cells and stroke brain tissue (in our stroke model). Identification of these and other proteins was proof of concept that low abundance biomarkers could be identified directly from cells and tissues especially with high pressure tissue extraction techniques using a Barocycler, Pressure Biosciences. The laboratory will be equipped for standard and micro 2D gel processing and transfer of sample to mass spectrometry systems with a new robotic integrated gel processing platform that performs gel imaging, spot cutting, digestion, extraction and transfer to MS systems, Shimadzu Xcise. Co-registration of tissue cryosections prepared in our laboratory allows subcellular imaging with MALDI and atomic force microscopy, Veeco. The direct imaging MALDI identification of proteins without extraction or modification of normal folding is a novel, rapid, robotic, method for identification of peptides and proteins from tissues and body fluids using both bottom-up and top-down proteomics. Additional studies have expanded the gamut of identified proteins in body fluids and tissues including placentas of smokers and non-smokers. Our results predict that these markers will be found by imaging MALDI and mass spectrometry in plasma, spinal fluid, saliva, sputum, small bowel effluent, and stool. The laboratory develops techniques of specimen preparation, matrix purification, and enzyme use, scaled for studies of low abundance markers in complex tissues/fluids using matrix chemistry and MALDI plasma physics. Imaging MALDI could become the new paradigm for universal, non-invasive, low cost, patient acceptable, rapid, population-screening tests for biomarkers of health and disease. The considerable resources of the laboratory are available for processing of intra and extramural tissue and biomolecules.