Colon – Vanderbilt University School of Medicine
| Project Title: | Advanced Proteomics Technologies for Cancer Biomarkers | |
| Cancer Site: | Colorectal | |
| Participating Institutions: | Vanderbilt University School of Medicine | |
| Mouse Model(s): | None | |
| Technical Approaches: |
Shotgun proteomics
Targeted protein quantitation MALDI Tissue Profiling/Imaging PTM mapping Development of algorithms and software |
|
Brief Description of Project:
The Vanderbilt ICBC team will focus on the application of mass spectrometry (MS)-based technologies to the discovery and quantitation of protein biomarkers for colorectal cancer. This team will build on an exceptionally strong existing infrastructure in MS and proteomics at Vanderbilt. Three major technology development areas are the application of MALDI-MS to direct proteomic analysis of tissues, the high-throughput analysis of tissue and biofluid proteomes by shotgun proteomics methods and quantitative analysis of specific proteins and protein forms of interest by targeted tandem mass spectrometry methods. The Vanderbilt team will be supported by a rapidly growing bioinformatics group in the Mass Spectrometry Research Center, which will develop and implement data analysis tools and standards that emphasize open-source applications and compliance with the National Cancer Institute caBIG initiative.
Team Members and Expertise:
Daniel C. LIEBLER, Ph.D. [daniel.liebler@vanderbilt.edu]
Dr. Liebler is Professor of Biochemistry, Pharmacology, and Biomedical Informatics at Vanderbilt and has been Director of the Proteomics Laboratory in the Mass Spectrometry Research Center (MSRC) since his arrival at Vanderbilt in 2003. Dr. Liebler has developed a strong research program in proteomics, with a principal emphasis on studies of protein modifications and damage by reactive intermediates in drug and chemical toxicity and in oxidative stress. His laboratory has developed MS-MS-based analytical methods and bioinformatics tools for the detection of modified proteins and peptides, including the SALSA and P-Mod algorithms. Dr. Liebler is Director of the Jim Ayers Institute for Precancer Detection and Diagnosis, which was founded by a $10M gift to Vanderbilt to apply proteomics technologies to discover markers for early detection and individualized therapy of colon cancer.
Richard M. CAPRIOLI, Ph.D. [richard.m.caprioli@vanderbilt.edu]
Dr. Caprioli is the Stanley Cohen Professor of 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. He is the Co-Editor of the Encyclopedia of Mass Spectrometry (Elsevier). In 2003, Dr. Caprioli received the Thomson Medal Award from the International Mass Spectrometry Society for "for outstanding achievements in mass spectrometry and for distinguished service to international mass spectrometry." He received the Field and Franklin Award for Contributions to Mass Spectrometry from the American Chemical Society in April, 2006. Professor Caprioli is interested in the use of mass spectrometry for the analysis of compounds in biological systems. Current work includes the use of electrospray and laser desorption ionization methods with biological tissues and samples. Applications to specific research areas involve questions about certain spatial distributions of molecules within specific tissues, e.g., mapping proteins in cancer tissue.
Robert J. COFFEY, M.D. [robert.coffey@vanderbilt.edu ]
Dr. Coffey is Professor of Medicine and Cell and Developmental Biology. He presently occupies two endowed chairs - the Ingram Professor of Cancer Research and the John B. Wallace Chair of Medicine. Dr. Coffey has directed the GI Cancer Program since the inception of the Vanderbilt-Ingram Cancer Center in 1994. He is PI of the Vanderbilt Mouse Models of Human Cancers Consortium (MMHCC) grant. Twenty elite institutions are funded through this NCI initiative that is designed to develop mouse models of cancer that simulate their human counterparts; these models are then used to develop innovative approaches to the diagnosis and treatment of cancer. Vanderbilt's MMHCC grant is focused on colorectal cancer. Dr. Coffey also directs Vanderbilt's GI Special Program of Research Excellence (SPORE) grant. This NCI-funded, multi investigator grant is also focused on colorectal cancer. Dr. Coffey is the only individual in the country to direct both a MMHCC and SPORE grant. Dr. Coffey is a member of The American Society of Clinical Investigation and the American Association of Physicians.
David L. TABB, Ph.D. [david.l.tabb@vanderbilt.edu]
Dr. Tabb is an assistant professor in the Departments of Biomedical Informatics and Biochemistry. He has worked in the field of proteomics since 1996, producing algorithms for a variety of applications. While completing his graduate studies in John Yates' laboratory, Dr. Tabb created the DTASelect and Contrast algorithms, widely used systems for proteomic data mining and comparative analysis. He also authored the GutenTag algorithm for inferring partial sequences from tandem mass spectra. In collaboration with Vicki Wysocki's group at the University of Arizona, Dr. Tabb published papers on the low-energy fragmentation of peptides. During his post-doctoral fellowship at Oak Ridge National Laboratory, he developed the DBDigger database search engine and MS2Grouper proteomic redundancy reducer to improve data analysis performance for high-volume collections of tandem mass spectra. At Vanderbilt, his group has focused on the problems of identifying modified and mutated peptides in the context of biomarker discovery in clinical proteomics.
Amy-Joan L. HAM, Ph.D. [amy.ham@vanderbilt.edu]
Dr. Ham is Research Assistant Professor of Biochemistry and Associate Director of the Proteomics Laboratory in the Mass Spectrometry Research Center at Vanderbilt. Dr. Ham has extensive research experience in the application of MS approaches to bioanalytical problems. She is experienced in the application of LC-MS-MS to the identification of multiprotein complexes and complex subproteomes and the mapping of protein modifications. She is a member of the MSRC bioinformatics group and has contributed to the design and implementation of several bioinformatics tools in use and development, including CHIPS, P-Mod, ScanDenser, the MSRC LIMS and other tools described in this application. She has led work on the development of data-independent scanning methods with the Thermo LTQ and Orbitrap instruments, which is a major focus of this project.
Lisa J. ZIMMERMAN, Ph.D. [lisa.zimmerman@vanderbilt.edu]
Dr. Zimmerman is a Research Instructor in the Biochemistry Department at Vanderbilt University and Associate Director in the Tissue Imaging Core Facility. Since 2003 she has been directed biofluid proteomics studies for the Tissue and Serum Proteomics core with a focus on method development for the analysis of tissue and biological fluids using both MALDI-MS and shotgun proteomic platforms for biomarker discovery. She has published on the identification of protein modifications by mass spectrometry, the analysis of serum proteomes and the correlation of MALDI-MS and shotgun proteome analysis MS-MS data.
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