Clinical Proteomic Technology Assessment for Cancer (CPTAC) Teams

Dr. Carr leads the Proteomics and Biomarker Discovery efforts at the Broad Institute of MIT and Harvard. His current research involves development and application of novel, quantitative approaches for biomarker discovery and validation as well as phosphoproteomics to understand drug and disease mechanisms and provide biomarkers for human cancers, heart disease and metabolic disorders. The Carr lab collaborates with biologists and chemists to systematically identify proteins and their modifications whose abundance or form is modulated by disease or drug action, as well as to define physical and functional associations of protein constituents of regulatory and signaling pathways involved in health and disease. These studies involve analysis of complex biological specimens, such as tumor tissues or patient blood using protein chemistry and advanced separation methods together with state-of-the-art mass spectrometry.

For the last 25 years, Dr. Carr's research has focused on applying and developing proteomics methods in order to understand the mechanism of action of drug candidates and build an understanding of protein targets and their roles in disease. He is noted for developing methods for selective enrichment, detection and quantitation of posttranslational modifications such as phosphorylation and glycosylation in the proteome. While at GlaxoSmithKline (1984-2001) and Millennium Pharmaceuticals (2001-2004), he made significant contributions to the discovery and development of four marketed drugs (small and large molecule) and to numerous drugs in clinical trial. His groups at GSK and Millennium also produced one of the first examples of proteomics-derived biomarkers in use in the clinic and the first example of de-orphaning of a G-coupled protein receptor by mass spectrometry. He has over 130 peer-reviewed publications on development and use of proteomics and biological mass spectrometry. Dr. Carr is an Associate Editor of Molecular and Cellular Proteomics, and he has served on the editorial boards of Analytical Chemistry and Protein Science, among others.

Dr. Carr received his B.S. in 1976 from Union College and Ph.D. from MIT in 1980. After four years of postdoctoral training at Harvard Medical School and MIT, he joined SmithKline Pharmaceuticals (now GlaxoSmithKline), becoming director of Computational and Structural Sciences in 1997. Most recently he led protein science and proteomics groups at Millennium Pharmaceuticals in Cambridge, MA, prior to joining the Broad Institute in 2004.

Dr. Tempst leads a proteomics research team specializing in R&D of protein / peptide microanalysis, with applications in chromatin dynamics research and cancer biomarker discovery. He is a Member of the Sloan-Kettering Institute and Professor at the Gerstner Sloan-Kettering Graduate School of Biomedical Sciences, as well as Professor of Molecular Biology at the Weill Graduate School of Medical Sciences, Cornell University. He provides executive oversight of the microchemistry, proteomics, genomics and engineering resource laboratories at his host institution. He has over 25 years of experience in protein chemistry and biochemistry, and mass spectrometry, and he has collaborated with investigators worldwide to identify and characterize novel and unknown interacting proteins and protein complexes.

His research is documented in over 230 peer-reviewed papers on proteomics methods and applications, mostly to study the mechanisms of transcriptional regulation. He is an inventor on several patents, including microfluidics-based automated chemistries, a continuous nano-electrospray ion source for mass spectrometry, Gallium-affinity chromatography of phosphopeptides, a protein-nitrosylation assay, and antibody micro-arrays with multi-layered affinity detection. Recently, his lab developed a novel platform for serum peptidome analysis and advanced the model that cancer type-specific peptide patterns are surrogate markers for changing exoprotease panels.

Dr. Tempst obtained a B.S. (1976) and Ph.D. (1981) at Ghent University in his native Belgium. He received a NATO Research Fellowship to conduct postdoctoral studies (1982-85) in the laboratory of Dr. Leroy Hood at the California Institute of Technology, where he was involved in the development of the earliest microchemistry systems. He later received a Leukemia Society of America Special Fellow Award and the Irma Hirschl Trust Career Scientist Award for the application of these novel technologies in molecular biology, genetics and medicine. He was a faculty member at the Harvard Medical School (1986-90) before taking up his current positions in New York in 1991.

After completing a Ph.D. at Oklahoma State University (1965) and Post Doctoral work at the University of Chicago (1966) and Harvard (1968), Professor Regnier became an Assistant Professor of Biochemistry (1968) at Purdue University. During twenty years in Biochemistry at Purdue he was an Associate Professor (1971-76), Professor (1976-90) and Associate Director of the Agricultural Experiment Station (1976-78). He became a Professor of Chemistry in the Chemistry Department at Purdue in 1990 and was promoted to Distinguished Professor in 2004. He is the author of over 300 publications, 40 patents, and several books on various aspects of chemistry, biochemistry, and particularly separation science and immunological assays as they relate to proteins.

Professor Regnier has for several decades been involved in the transfer of technology to society through patents from his laboratory, company creation, and continuing education. Along with Professor Barry Karger (Northeastern University), he co-founded Bioseparations in 1984 to provide advanced courses in analytical chemistry to scientists in the pharmaceutical industry. During the course of the next four years Bioseparations presented courses to more than a thousand scientists in U.S and European pharmaceutical companies. He then co-founded PerSeptive Biosystems (PBIO) with Noubar Afeyan in 1988 based on licensed Purdue technology, and actively participated in the growth of that company to 500 people in the U. S., Europe, and Asia. The sale of large-scale pharmaceutical manufacturing systems and scientific instruments by PBIO to more than 300 pharmaceutical and biotechnology companies grew to $100 million in 1997, when the company was sold to Applied Biosystems (ABI). In 2000, he co-founded Beyond Genomics (BG) with Jan van der Greef (University of Leiden), David Clemmer (Indiana University), and Scott McLuckey (Purdue University). BG provides advanced drug discovery tools to the pharmaceutical and biotechnology industry. The company has grown to 60 people with facilities in Europe and North America and has ongoing drug discovery relationships with major pharmaceutical companies. Most recently, he co-founded Quadraspec with David Nolte, Chard Barden, and Eric Davis. The focus of Quadraspec is on very high throughput immunological assay technology for health assessment.

Susan Fisher, Ph.D., is currently a Professor of Cell and Tissue Biology and the Faculty Director for the Biomolecular Resource Center Mass Spectrometry Center. Her research is focused on many aspects of reproductive biology as well as the biomedical applications of mass spectrometry. She has received numerous honors throughout her career, including an achievement award from the Society for Women's Health. Fisher received her Bachelor degree from Hope College in Holland, Michigan, and her Ph.D. degree from the University of Kentucky, where she also completed a postdoctoral fellowship in mass spectrometry.

Dr. Daniel C. Liebler received a Ph.D. in Pharmacology from Vanderbilt while training in the laboratory of F. Peter Guengerich. He did postdoctoral training in the laboratory of Donald J. Reed at Oregon State University. From 1987-2003, Dr. Liebler served on the faculty of the Department of Pharmacology and Toxicology in the College of Pharmacy at the University of Arizona. From 1987 to 1998, his research program focused on the mechanisms of action of antioxidants in prevention of oxidative damage and cancer. His group defined antioxidant pathways and mechanisms of antioxidant action of vitamin E, carotenes and flavonoid antioxidants and established the use of mass spectrometry (MS)-based assays for products of antioxidant reactions as markers of antioxidant function. Since 1998, Dr. Liebler's program has focused on the application of MS-based proteomics approaches to address the problem of how reactive chemical intermediates cause damage to proteins.

The Liebler group developed two data analysis tools, SALSA and P-Mod, which enable discovery of modified protein forms through analysis of MS data, even when the chemical nature and sequence specificity of the modifications are not known beforehand. This approach has been integrated with affinity capture methods to evaluate electrophile-mediated protein damage on a proteomic scale and map over 1500 sites of chemical modification on over 800 human proteins. Dr. Liebler's laboratory has also extended these proteomic approaches to analyze the role of site-specific modifications in the function of signaling and sensor proteins that regulate responses to chemical toxicity and oxidative stress. The mapping of modifications has been augmented by application of stable isotope tagging methods to analyze the kinetics of protein modification reactions.

Dr. Liebler relocated to Vanderbilt in June 2003, where he has served as Director of Proteomics in the Mass Spectrometry Research Center. The Proteomics Laboratory has implemented methods and approaches developed in Dr. Liebler's laboratory and serves over 130 research groups at Vanderbilt. Most recently, Dr. Liebler has accepted Directorship of the Jim Ayers Institute for Precancer Detection and Diagnosis, which is dedicated to the discovery of proteomic markers for early cancer detection and for guiding therapy of established disease. Dr. Liebler's long-term research goals are to apply proteomics and related emerging technologies to identify markers of disease, therapeutic effect and toxicity and to characterize the roles of protein damage in chemical toxicity and disease.