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As Proteomics Evolves, Thermo's BRIMS Starts Validating Markers, Building Assays

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When Thermo Fisher Scientific opened the Biomarker Research Initiatives in Mass Spectrometry center in late 2004, the intent was to develop mass spectrometry-based technologies for biomarker discovery, especially in the area of cardiovascular disease.
 
But as proteomics research matures, the Cambridge, Mass.-based center has shifted its focus from identifying proteins to validating biomarkers and developing clinically applicable assays. It will continue performing biomarker discovery work.
 
“As proteomics evolved so did we, and as proteomics has gone from a science that was really more discovery based into a science that is becoming now more quantitative and has applications in the clinical world, that is how our focus is also shifting,” said Mary Lopez, who took over as head of the 3,000-square-foot center about two months ago.
 
In coming months, the changes will become more apparent as the center announces collaborations it is finalizing with “key opinion leaders [who] are engaged in biomarker research,” said Lopez, who declined to elaborate.
 
Entering Adolescence
 
When BRIMS first opened three-and-a-half years ago, the focus of many proteomics research was still on the discovery phase. But since then, the field has matured, and the technology demanded by researchers has become more sophisticated, necessitating a change in the center’s goals, Lopez said.
 
“A big focus of BRIMS now will be to work on our [TSQ Quantum] triple-quadrupole platform … and to develop targeted high resolution [selective reaction monitoring] and [multiple reaction monitoring] assays for peptides and protein biomarkers using that instrumentation,” Lopez told ProteoMonitor recently.
 
“The nice progression from the biomarker discovery work … can now be ported to more quantitative, clinically focused assays that we can develop on the Quantum,” she added. “And that work will be prototyped at BRIMS.”
 
Other instruments outfitted at the center include the LTQ Orbitrap hybrid mass spec, LTQ FTMS, LTQ XL mass spec, and the KingFisher technology for sample separation.
 
Thermo will continue working on cardiovascular biomarkers, but in other collaborations being discussed, Thermo plans to extend the center’s work to include areas such as cancer, macular degeneration, and metabolic disorders.
 
“There are many different areas that are interesting to researchers out there and we had a desire to demonstrate how our technology can facilitate research in other disease areas,” she said.
 
But instead of focusing on particular diseases, the center will aim to develop and improve workflows for proteomics researchers, and develop quantitative assays. The new emphasis, Lopez said, is meant to keep BRIMS in step with where proteomics is heading.
 
Indeed, proteomics experts have been increasingly encouraging their colleagues to perform more quantitative research, while researchers have bemoaned the lack of technology that allows them to do so.
 
With the research community increasingly moving toward quantitative work, Lopez said, the next step, at least in the clinical arena, is to develop robust assays that allow scientists to go after well-defined targets.
 
While BRIMS was already moving in that direction prior to Thermo’s merger with Fisher Scientific last fall, that deal accelerated the transition by giving the company the chemistry know-how and product portfolio it didn’t have before, Lopez said.
 
“We have all of the Pierce products and the Fisher consumables and even diagnostic and clinical reagents there, and to couple that with the high-resolution mass spectrometers … that’s a tremendous power,” she said. Pierce Biotechnology is a unit of Thermo Fisher.
 
Cardiovascular at First
 
Originally, BRIMS was created as a way for Thermo to perform mass-spec experiments without having to shuttle samples from different collaborator sites at different stages of the research. At the time, Thermo had cardiovascular biomarker collaborations with, among others, Massachusetts General Hospital, Harvard Medical School, Brigham and Women’s Hospital, and Children’s Hospital.
 

“As proteomics evolved so did we, and as proteomics has gone from a science that was really more discovery based into a science that is becoming now more quantitative and has applications in the clinical world, that is how our focus is also shifting.”

The company initially chose to concentrate on cardiovascular biomarker work, Thermo said in 2004, because patient response could be more rapidly induced with cardiology than with diseases such as cancer, whose drugs take longer to show efficacy.
 
Thermo also chose to partner with Massachusetts General on BRIMS at the time because the hospital had a large quantity of well-annotated plasma samples from well-characterized clinical trials of patients with cardiovascular disorders [See PM 10/15/04].
 
The hospital’s formal relationship with BRIMS ended last December, but Lopez told ProteoMonitorthat Thermo and the Massachusetts General researcher who did most of the cardiovascular biomarker work have been in “informal discussions” to evaluate what relationship they may have going forward.
 
Lopez shied away from saying whether any biomarkers were identified as a result of its partnership with the hospital, saying only that “We made tremendous progress in that area.”
 
Massachusetts General declined to comment on the collaboration.
 
One product that was developed at BRIMS was Thermo’s SIEVE software designed for label-free differential protein expression analysis. Launched at the American Society for Mass Spectrometry conference last June, the technology offers an automated workflow for comparison of LC/MS analyses from large sample preparations [See PM 06/01/06].
 
“The BRIMS continues to add features to that software [and] to work very closely with the researchers and developers at our San Jose office to extend the features,” Lopez said.
 
The center currently has five employees, all researchers and bioinformaticians, and is looking to add two more employees, Lopez said. She declined to comment on the cost of running the center.

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