October 3, 2003

Liebler joins VUMC to expand Proteomics

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Daniel Liebler, Ph.D. said the diversity and quality of biomedical research at Vanderbilt will make the institution a strong player in the field of proteomics. Dana Johnson

Liebler joins VUMC to expand Proteomics

Part three of four

In this series, the Reporter is highlighting progress made by the Vanderbilt Institute of Chemical Biology during its first year. Daniel Liebler, Ph.D., a co-recruit of the VICB and the department of Biochemistry, has taken the reins of the Proteomics Laboratory and will expand the technologies and services offered to Vanderbilt investigators. Next week, the Reporter will introduce the new director of the Program in Translational Neuropharmacology and his role in making high-throughput screening of small molecules available to researchers interested in dissecting biological systems or in identifying potential therapeutic agents.

Daniel Liebler’s ninth floor office in Medical Research Building III looks out over the entire Medical Center. This, he says with a sweep of his hand across the view, is Vanderbilt’s greatest strength in proteomics and what drew him to lead the institution’s efforts in the area.

“What drives innovation in proteomics is really interesting research problems,” said Liebler, Ph.D., professor of Biochemistry and director of Proteomics. “The better and more diverse the problems, the better proteomics gets, the better any core facility gets. The real strength of our proteomics here is the tremendous depth and scope of biomedical research that’s going to drive us to do things differently.”

Proteomics is, put simply, the study of everything about proteins and how they work. “Just about all biology that’s done by the cells and tissues that we study in health and disease really involves the function of proteins, and so everyone has to be doing proteomics at some level in their research,” Liebler said.

Vanderbilt has had a proteomics resource as part of the Mass Spectrometry Research Center for a few years, but Liebler’s arrival marks an expansion of the services that will be offered.

“We needed a leader who would be able to translate the work from the basic research lab into services and collaborations,” said Richard Caprioli, Ph.D., Stanley Cohen Professor of Biochemistry and director of the Mass Spectrometry Research Center.

“Dan was recruited because of his exceptional talents in the area of proteomics — how you do it at the bench level — and for his ability to translate that into working with other scientists and clinicians.”

“We couldn’t be more pleased that Dan has joined us to lead our effort in Proteomics. We are very fortunate,” said Michael R. Waterman, Ph.D., Natalie Overall Warren Distinguished Professor and Chair of Biochemistry. Liebler was recruited by the department of Biochemistry and the Vanderbilt Institute of Chemical Biology.

“There is every reason to believe that with Dan’s assistance, the Mass Spectrometry Research Center will become not just one of the best such centers in the world, but the best,” Waterman added.

Proteomics uses mass spectrometry as a tool for identifying proteins — in complex biological mixtures and in tissues. The term proteomics is “kind of a buzzword that represents a collection of tools, and application of those tools is still at an early stage,” Liebler said.

One application that is generating excitement is the use of proteomics to determine “molecular fingerprints” for disease. Using a technology developed by Caprioli and colleagues, Vanderbilt investigators recently demonstrated that a distinct pattern of expression of 15 proteins in lung cancers can predict a poor or a good prognosis.

The protein profiles also can be used to predict risk that the cancer has spread to nearby lymph nodes, an important factor in determining treatment strategies.

“It’s clear that the next wave of what we do in research, medicine, and patient care is going to have to do with molecular events — our understanding of the molecular basis of disease – not only for diagnosis, but also for prognosis and treatment,” Caprioli said. “Proteomics is a big part of this kind of predictive, individualized medicine.”

Vanderbilt’s Proteomics Laboratory offers the “complete menu of analytical proteomics instrumentation,” Liebler said, including the newest generation of mass spectrometers from Thermo Electron Inc. and Applied Biosystems. The laboratory also has established interactions with excellent biostatistics and bioinformatics/supercomputing groups, led by Yu Shyr, Ph.D. and Jason Moore, Ph.D., respectively. Any Vanderbilt investigator interested in pursuing a proteomics approach is encouraged to make use of the laboratory.

“There’s really no place I know of that has this kind of a resource, that’s made this type of investment in proteomics,” Liebler said. “You don’t have to be Richard’s or my pal to do great work in proteomics.”

Liebler hopes to develop what he calls a “culture of proteomics” at Vanderbilt, a culture where investigators know how to design experiments that will make the best use of the available proteomics technologies. He plans to launch a proteomics journal club in the near future, and he will be teaching a graduate level course in proteomics starting next spring. The laboratory will also host workshops periodically on more specific applications.

To aid the scale-up in proteomics throughput, the facility will make heavy use of automation. And users will be engaged in as many phases of the analytical proteomics process as possible and in data analysis, Liebler said.

“One of the big bottlenecks in proteomics research is the tremendous volume of data generated by the experiments,” he said. “Reassembling the data in a biologically meaningful context is a big task in itself.”

Liebler’s group has been developing a database and software program called CHIPS (Complete Hierarchical Integration of Protein Searches), which provides a means of organizing proteomics data through a browser-based interface. “It’s what we call bio-friendly; you don’t have to be a mass spec genius to deal with the data,” Liebler said.

Three associate directors are in charge of day-to-day operations of the facility. David Friedman, Ph.D., Amy Ham, Ph.D., and Lisa Zimmerman, Ph.D. each have expertise in different aspects of proteomics and are available for consultation with interested investigators.

Liebler was “lured into proteomics,” he said, by his own research interests, which focus on protein modifications, particularly by reactive chemicals involved in chemical toxicity. Protein modifications are also part of normal cell biology and are one of the main things that dictate how proteins behave — “whom they shake hands with and when they exit the stage,” Liebler said.

His team at the University of Arizona developed new analytical methods and software to identify protein modifications. Their program SALSA (Scoring Algorithm for Spectral Analysis) is a tool for mining mass spectrometry data to identify spectra that correspond to modified, variant forms of proteins.

The software was licensed to Thermo Electron, Inc. and is now supplied to users all over the world as part of the manufacturer’s software package.

The Proteomics Laboratory at Vanderbilt is flanked by Liebler’s and Caprioli’s research laboratories. “The juxtaposition of research labs developing new technologies and a core that can help to quickly translate those technologies into practice for other investigators at Vanderbilt is a recipe for an effective proteomics laboratory,” Liebler said.

The tissue profiling and imaging technology developed by Caprioli’s team, for example, is already available as part of the Proteomics Laboratory. Most places do not have this innovative technology, Liebler said.

Liebler is no stranger to Vanderbilt. He completed his Ph.D. degree here in Pharmacology, under the mentorship of F. Peter Guengerich, Ph.D., professor of Biochemistry and director of the Center in Molecular Toxicology. Guengerich’s lab at the time was on the first floor B corridor in Medical Center North.

It feels odd, Liebler said, that he’s come “20 years, 50 feet over, and nine floors up,” but he couldn’t be happier about returning to Vanderbilt.

“In the areas of molecular chemical toxicology and the interface between chemistry and biology that I consider my research home, this is the place to be, period, end of discussion.”

Liebler completed postdoctoral training with D. J. Reed, Ph.D. at Oregon State University and served on the faculty at the University of Arizona for 16 years. At Arizona, he was the director of the Center for Toxicology, the Toxicology Training Program, and the Proteomics Core Laboratory.

He has chaired the National Institutes of Health Chemical Pathology Study Section and delivered multiple invited lectureships. Liebler is the author of a textbook on proteomics, “Introduction to Proteomics: Tools” for the New Biology", published in 2002, and he is currently a co-chair for the 2005 Gordon Research Conference on Toxicogenomics.