Richard M. Caprioli is the Stanford Moore Chair in Biochemistry and Director of the Mass Spectrometry Research Center at Vanderbilt University School of Medicine. He is also currently Professor in the Departments of Chemistry and Pharmacology at Vanderbilt University. Dr. Caprioli received his B.S. in 1965 from Columbia University in New York, N.Y., his Ph.D. in 1969 in Biochemistry, also at Columbia University with Professor David Rittenberg. He did a one-year postdoctoral fellowship at Purdue University with Professor John H. Beynon. In 1970, he was appointed as Assistant Professor of Biochemistry at Purdue. In 1975, Dr. Caprioli moved to the University of Texas Medical School in Houston where he was Professor of Biochemistry and Molecular Biology and Director of the Analytical Chemistry Center until his move to Nashville in February, 1998.
The research interests of this laboratory are aimed at the investigation of biological processes involving the synthesis, modification, storage and degradation of certain peptides and proteins using modern mass spectrometric methods of analysis to follow molecular events. In recent years there has been a great amount of interest in investigating the biochemical events involved in the metabolism of peptides, primarily in the brain and gut of mammals, encompassing the enzymatic breakdown of these peptides, their production from peptide and protein precursors, and the disruption of these processes by certain xenobiotics. Modern mass spectrometric techniques are used in these studies, including electrospray and matrix-assisted laser desorption ionization mass spectrometry. This research is generally carried out with two experimental approaches.
The first involves in vivo metabolic studies in live animals (rats) using microdialysis sampling procedures together with molecular identification and quantitation by electrospray tandem mass spectrometry. This experimental approach allows us to measure metabolic events that occur in freely moving animals at a level of 50-100 attomoles in the tissue dialysate. Integrated technology for microdialysis/mass spectrometry utilizes quadrupole mass spectrometry (MS/MS) and micro-electrospray ionization (micro-ESI) for very high sensitivity measurements. The micro-ESI source has been optimized to produce ions from the electrospray process at sub-microliter per min flow rates. The application of combined microdialysis/ESI mass spectrometry is ongoing in four areas, i) Investigation of the kinetics and quantitative aspects of the in vivo metabolism of the neuropeptides and enkephalin neuropeptides, ii) Studies of the kinetics and differential processing of opioid peptide fragment precursors in vivo, iii) Investigation of the in vivo quantitative production and enzymatic degradation of N-acetylaspartyl-glutamate in seizure disorders using a rat model, and iv) Development and measurements of in vivo drug pharmacokinetics, using the drugs haloperidol, valproic acid, cocaine, amphetamine, and the new GABA antagonist n-butyl-3 aminopropylphosphinic acid.
The second experimental approach used in the study of cellular peptide metabolism utilizes new molecular imaging technology that is being developed in our lab. This method involves molecular mapping of animal tissue through the production of ion images obtained from the analysis of mammalian tissue slices by matrix-assisted laser desorption mass spectrometry (MALDI MS)12. This technique permits a tissue section to be mapped in multiple molecular weight values, localizing the molecules in an X, Y coordinate representation of the sample. Ion images are produced by repetitive exposure of the sample to the laser beam, where adjacent spots are irradiated, resulting in an ordered array of mass spectra that are keyed to specific locations in the sample. From one raster of the sample, a specific ion image, at any chosen m/z value, could be produced to give the spatial arrangement of molecules of interest. Current work involves; i) Instrument development involving modifications to an existing commercial MALDI (TOF) mass spectrometer, including changes to the laser optics, target movement system, and instrument control hardware and software, ii) Development of methods for sample preparation and target surface modifications to achieve high sensitivity and high image resolution, with molecular specificity, and iii) Applications to specific research areas involving questions about certain spatial distributions of molecules within specific tissues.
Murphy AJ, Pierce J, Seeley EH, Sullivan LM, Ruchelli ED, Nance ML, Caprioli RM, Lovvorn HN 3rd. Peptide spectra in Wilms tumor that associate with adverse outcomes. Journal of Surgical Research.2015, pii: S0022-4804(15)00288-7. [Epub ahead of print]
Caprioli RM. Imaging Mass Spectrometry: Enabling a New Age of Discovery in Biology and Medicine Through Molecular Microscopy. Journal of the American Society for Mass Spectrometry. 2015. [Epub ahead of print]
Floyd KA, Moore JL, Eberly AR, Good JA, Shaffer CL, Zaver H, Almqvist F, Skaar EP, Caprioli RM, Hadjifrangiskou M. Adhesive Fiber Stratification in Uropathogenic Escherichia coli Biofilms Unveils Oxygen-Mediated Control of Type 1 Pili. PLoS Pathogens. 2015, 11(3):e1004697.
Van de Plas R, Yang J, Spraggins J, Caprioli RM. Image fusion of mass spectrometry and microscopy: a multimodality paradigm for molecular tissue mapping. Nature Methods. 2015. [Epub ahead of print]
Zavalin A, Yang J, Hayden K, Vestal M, Caprioli RM.Tissue protein imaging at 1 μm laser spot diameter for high spatial resolution and high imaging speed using transmission geometry MALDI TOF MS.Analytical and Bioanalytical Chemistry.2015, 407(8):2337-42.
Taverna D, Boraldi F, De Santis G, Caprioli RM, Quaglino D. Histology-directed and imaging mass spectrometry: An emerging technology in ectopic calcification. Bone.2015, 74:83-94.
Libes JM, Seeley EH, Li M, Axt JR, Pierce J, Correa H, Newton M, Hansen E, Judd A, McDonald H, Caprioli RM, Naranjo A, Huff V, O'Neill JA Jr, Lovvorn HN, Kenyan Wilms Tumor Consortium. Race disparities in Peptide profiles of north american and kenyan wilms tumor specimens. Journal of the American College of Surgeons. 2014, 218 (4): 707-20.
Caprioli RM. Imaging Mass Spectrometry: Molecular Microscopy for Enabling a New Age of Discovery. Proteomics. 2014, 0 (0): [Epub ahead of print].
Seeley EH, Wilson KJ, Yankeelov TE, Johnson RW, Gore JC, Caprioli RM, Matrisian LM, Sterling JA. Co-registration of multi-modality imaging allows for comprehensive analysis of tumor-induced bone disease. Bone. 2014, 61 (0): 208-16.
Kriegsmann M, Seeley EH, Schwarting A, Kriegsmann J, Otto M, Thabe H, Dierkes B, Biehl C, Sack U, Wellmann A, Kahaly GJ, Schwamborn K, Caprioli RM. MALDI MS imaging as a powerful tool for investigating synovial tissue. Scandinavian Journal of Rheumatology. 2012, 41 (4): 305-309.
Oswald-Richter KA, Beachboard DC, Seeley EH, Abraham S, Shepherd BE, Jenkins CA, Culver DA, Caprioli RM. Dual Analysis for Mycobacteria and Propionibacteria in Sarcoidosis BAL. Journal of Clinical Immunology. 2012, 32 (5): 1129-1140.
Attia AS, Schroeder KA, Seeley EH, Wilson KJ, Hammer ND, Colvin DC, Manier ML, Nicklay JJ, Rose KL, Gore JC, Caprioli RM, Skaar EP. Monitoring the Inflammatory Response to Infection through the Integration of MALDI IMS and MRI. Cell Host & Microbe. 2012, 11 (6): 664-673.
Thiery G, Mernaugh RL, Yan HP, Spraggins JM, Yang JH, Parl FF, Caprioli RM. Targeted Multiplex Imaging Mass Spectrometry with Single Chain Fragment Variable (scfv) Recombinant Antibodies. Journal of the American Society for Mass Spectrometry.2012, 23 (10): 1689-1696.
Seeley EH, Caprioli RM. 3D Imaging by Mass Spectrometry: A New Frontier. Analytical Chemistry. 2012, 84 (5): 2105-2110.
Yang JH, Chaurand P, Norris JL, Porter NA, Caprioli RM. Activity-Based Probes Linked with Laser-Cleavable Mass Tags for Signal Amplification in Imaging Mass Spectrometry: Analysis of Serine Hydrolase Enzymes in Mammalian Tissue. Analytical Chemistry. 2012, 84 (8): 3689-3695.
Lazova R, Seeley EH, Keenan M, Gueorguieva R, Caprioli RM. Imaging Mass Spectrometry-A New and Promising Method to Differentiate Spitz Nevi From Spitzoid Malignant Melanomas. American Journal of Dermatopathology. 2012, 34 (1): 82-90.
Yang JH, Caprioli RM. Matrix Sublimation/Recrystallization for Imaging Proteins by Mass Spectrometry at High Spatial Resolution. Analytical Chemistry.2011, 83 (14): 5728-5734.
Seeley EH, Schwamborn K, Caprioli RM. Imaging of Intact Tissue Sections: Moving beyond the Microscope. Journal of Biological Chemistry. 2011, 286 (29): 25459-25466.
Chacon A, Zagol-Ikapitte I, Amarnath V, Reyzer ML, Oates JA, Caprioli RM, Boutaud O.On-tissue chemical derivatization of 3-methoxysalicylamine for MALDI-imaging mass spectrometry. Journal of Mass Spectrometry. 2011, 46 (8): 840-846.
Manna JD, Reyzer ML, Latham JC, Weaver CD, Marnett LJ, Caprioli RM. Ma ZQ, Chambers MC, Ham AJL, Cheek KL, Whitwell CW, Aerni HR, Schilling B, Miller AW, Caprioli RM, Tabb DL. High-Throughput Quantification of Bioactive Lipids by MALDI Mass Spectrometry: Application to Prostaglandins. Analytical Chemistry.2011, 83 (17): 6683-6688.
Ma ZQ, Chambers MC, Ham AJL, Cheek KL, Whitwell CW, Aerni HR, Schilling B, Miller AW, Caprioli RM, Tabb DL. ScanRanker: Quality Assessment of Tandem Mass Spectra via Sequence Tagging. Journal of Proteome Research. 2011, 10 (7): 2896-2904.
Hardesty WM, Kelley MC, Mi DM, Low RL, Caprioli RM. Protein signatures for survival and recurrence in metastatic melanoma.Journal of Proteomics. 2011, 74 (7): 1002-1014.
Manier ML, Reyzer ML, Goh A, Dartois V, Via LE, Barry CE, Caprioli RM. Reagent Precoated Targets for Rapid In-Tissue Derivatization of the Anti-Tuberculosis Drug Isoniazid Followed by MALDI Imaging Mass Spectrometry. Journal of The American Society for Mass Soectrometry. 2011, 22 (8): 1409-1419.
Mainini V, Kliman M, Angel PM, Magni F, Caprioli RM. Detergent enhancement of on-tissue protein analysis by matrix-assisted laser desorption/ionization imaging mass spectrometry. Rapid Communications in Mass Spectrometry. 2011, 25 (1): 199-204.
Seeley EH, Caprioli RM. MALDI imaging mass spectrometry of human tissue: method challenges and clinical perspectives. Trends Biotechnol. 2011, 29(3): 136-43.
Ridenour WB, Kliman M, McLean JA, Caprioli RM. Structural Characterization of Phospholipids and Peptides Directly from Tissue Sections by MALDI Traveling-Wave Ion Mobility-Mass Spectrometry. Analytical Chemistry. 2010, 82 (5): 1881-1889.