This story originally ran on June 15.
A proteomics center, the final piece of an initiative created two years ago to bring proteins to the forefront of personalized medicine, is scheduled to become operational by the end of the summer, according to officials.
In late May, the Translational Genomics Research Institute named Konstantinos Petritis the first head of the Center for Proteomics in anticipation of opening its doors in August and performing what many see as the next step in bringing proteomics to the mainstream — the validation of biomarkers.
In the meantime, construction of the center, located in Phoenix, Ariz., is being completed, staff is being hired, and officials are in the final stages of choosing instruments, including mass specs, for the 3,400-square-foot space.
Other instruments and tools in the lab will include liquid chromatographs, plate readers, immunoprecipitation instruments, and thermal mixers. Eventually the staff will number 12 to 15 full-timers and post-docs whose numbers will depend on the number of research projects underway at the center.
The center is the final component of an initiative called the Partnership for Personalized Medicine, started in 2007 to try to realize the potential of personalized medicine through the use of protein biomarkers. Along with TGen, the partnership includes the Fred Hutchinson Cancer Research Center and Arizona State University's Biodesign Institute.
Funding for PPM came from the Virginia G. Piper Charitable Trust, which contributed $35 million, and the Flinn Foundation, which provided $10 million.
While discussions about personalized medicine have often centered on the role of genomics, PPM was founded to try to capitalize on the potential of proteins to diagnose, predict, and cure diseases.
A fact sheet from the Piper trust says that proteins will be "more informative than DNA or RNA as a basis for diagnostic tests and can be applied to a broader spectrum of diseases" because of the changes in proteins that accompany changes in physiological conditions; the greater variation of proteins present in disease states; and the easy accessibility of blood, which contains the proteins from diseased tissue.
The goals of the partnership are twofold — to reduce healthcare costs, and to translate scientific discoveries into diagnostics and treatments.
By aligning high-throughput biology with healthcare economics, PPM can begin to address "whether we can actually take a biomarker for a given specific situation in a clinical context [and] reduce healthcare costs," Jeffrey Trent, president and research director of TGen, told ProteoMonitor last week.
To answer that question, PPM officials decided they needed first to "think of single-payer nations, rather than try to figure out how to do this within the environment of the US healthcare system," with its jumble of private and public payers, Trent said. The first demonstration project PPM established was with Luxembourg, looking at lung cancer, which the TGen Center for Proteomics will continue working on as its initial project.
The center will focus on the discovery and validation of biomarkers for lung cancer.
TGen has two other projects with Luxembourg "to help turn that country into Europe's premier biomedical center," TGen said in a statement: the Integrated BioBank of Luxembourg to create a repository for tissue samples, and the Center for Systems Biology Luxembourg, which will track the genetic basis of disease and develop protein-based tests. The Institute for Systems Biology, which is not part of PPM, is the lead institute in the last project.
Patrizia Luchetta, deputy director for the Board of Economic Development for Luxembourg's Ministry of the Economy and Foreign Trade, said that the country had been searching for potential partners for projects aimed at jumpstarting Luxembourg's developing biotech industry.
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As a small country, Luxembourg had to target an area of interest rather than take a broad, multi-pronged strategy, and "as the aim of personalized medicine gets closer and with all the technological advances that have happened in proteomics, molecular diagnostics seems to be one of the potential successful niches," Luchetta said. Because of the costs involved — Luxembourg is investing €140 million ($193 million) over five years into the three projects, including €13 million over three years for the lung cancer project — it was also important that the citizens of the country could reap any rewards resulting from the efforts, she added.
"Being able to work on a subject where you can say, 'Well, we can maybe hopefully, if not decrease, then at least contain healthcare costs and also offer better therapies to our citizens,' then that's a good way to go," she said.
The partners are currently estimating how much cost savings may result from the work with TGen and expect to publish a report on their findings in November, Luchetta said.
Why a Proteomics Center?
But with the Hutch already doing extensive proteomics work, why would PPM create a dedicated proteomics center?
According to Petritis, the need for such a center arises from the demand for more validation in proteomics.
"Validation is an underrepresented area, and this is an area [which] we will specialize in," he told ProteoMonitor, adding that the Hutch's biomarker work is primarily in discovery. Work at the Center for Proteomics will comprise roughly 75 to 80 percent biomarker validation with the rest biomarker discovery, he said.
"We know what the problems have been," in biomarker validation, Petritis said, and the center will use the latest technology to solve them.
Petritis joins TGen from the Pacific Northwest National Laboratory where he was a senior research scientist in the Biological Separations and Mass Spectrometry/Proteomics group in PNNL's Environmental Molecular Sciences Laboratory.
Indeed, after more than a decade of shotgun discovery and the mining of thousands of candidate protein biomarkers across a range of diseases, many in the field are now pushing for greater emphasis on validation work. For example, Ruedi Aebersold, a co-founder of the Institute for Systems Biology and a professor of molecular systems biology at the Federal Technical University in Zurich and the University of Zurich, has been preaching the need for targeted validation for years [see PM 09/07/06].
Vendors such as Thermo Fisher Scientific and Life Technologies' Applied Biosystems, sensing a shift in momentum, are also developing validation tools and methods such as multiple-reaction monitoring, or MRM, workflows.
One MRM-based method that Petritis said he is particularly interested in is Stable Isotope Standards and Capture by Anti-Peptide Antibodies, or SISCAPA, a mass-spec based method developed by Leigh Anderson, CEO of the Plasma Proteome Institute [see PM 02/16/06].
Petritis and his staff also plan to automate the sample preparation process and are looking at forming partnerships with bioinformatics outfits to "integrate all the discovery and validation [data] in order to come up a pipeline that makes sense," he said.
According to Trent, another goal is "to establish this center for proteomics to do commercial-scale, industrial-scale throughput analysis at a non-profit, academic environment."
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That entails addressing an especially tricky part of proteomics that several groups are working on — developing workflow standards. As part of the process of choosing mass specs for the center, Petritis and his staff are "matching the workflow front end with the machine back end," and determining how to modify different SOPs with product lines in order to bring "a robust, industry standard quality control to the front end," Trent said.
The center's own work in the area will draw upon other standards- and protocol-development efforts — such as those by the Human Proteome Organization and its Proteomics Standards Initiative, the research groups of the Association of Biomolecular Resource Facilities, and the National Cancer Institute's Clinical Proteomic Technology Assessment for Cancer program — and adjusting those recommendations to fill its own needs.
"There aren't as many groups excited about doing the same thing 10, or 100, or 1,000 times as there are people who just want to do the next discovery," Trent said. "And the idea of standardization … around the SOPs and putting this through a high-throughput environment … is really what I think distinguishes" the TGen Center for Proteomics from other proteomics labs.
During the next six months, Petritis will be evaluating various QA/QC approaches to minimize variability in data, as well as performing pilot studies. Within that time, he added, he expects the center will begin validating biomarkers from Mandy Paulovich's laboratory at the Hutch in connection with the Luxembourg lung cancer project.
Along with the eventual development of diagnostic tests, the lung cancer work may yield tools to help clinicians determine the disease stage of a patient and the most appropriate course of treatment.
Though PPM is proteomics-directed, Petritis and his staff will also benefit from TGen projects in other research areas. "There's an advantage to having a group like TGen involved to align at the same time in the discovery setting orthogonal datasets of genomic sequence information, knowledge mining, all this stuff that weaves into the kind of work that [Petritis] is doing," Trent said.
All work at the center will be mass spec-based. There are no plans to do protein array research, though there could be collaborations at some point with Joshua LaBaer, who was recently named the director of the new Virginia G. Piper Center for Personalized Diagnostics at the Biodesign Institute. He had been the director of the Harvard Institute of Proteomics where he developed an array technology called Nucleic Acid Programmable Protein Array, or NAPPA.
A spokeswoman for the Hutch said that officials would not be available for comment, but in a statement announcing the naming of Petritis, Lee Hartwell, president and director of the Hutch, said that establishing the TGen Center for Proteomics is "integral to the success of" PPM.
While PPM-related work will be the first priority for the TGen Center for Proteomics, Petritis said that it would eventually collaborate with other non-profit and academic centers, as well as commercial firms on projects. There will also be a fee-for-service component to its business, he added.
TGen is also in conversations "with multiple groups" including private health insurers in the US for other possible projects, Trent said.