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Step by Step, a Better Mass Spec

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  • Title: Senior Scientist, Pacific Northwest National Laboratory
  • Education: PhD, University of Florida at Gainesville, 2002
  • Recommended by: Dick Smith

For Wei-Jun Qian, the appeal of a place like the Pacific Northwest National Laboratory comes down to technology development. "This place is really so technology-oriented," he says, "it's a great place for me to integrate lots of different techniques."

Qian has long been involved in developing ways to improve technology. Proteomics has always been known for its difficulty with quantification, and that is one area where Qian has spent a good deal of time. Particularly for clinical studies, he says, good quantification practices have been tough to come by. "Proteomics is so complicated, so complex," he says, noting that practitioners must be able to detect proteins of very low abundance in a sample for studies involving, say, a protein biomarker for disease.

Qian's goal is to marry the benefits of high-throughput biology with the advantages of a more targeted approach. "I'm trying to link global discovery with target validation," he says. This work relies on a triple-quadrupole mass spectrometer. Qian says he also works a lot on chemistry and labeling approaches to try to improve quantification as well.

At PNNL, his mandate is to use mass spec-based proteomics and to develop new methods for applying the technology. The idea is to improve scientists' ability to study post-translational modifications, cell signaling, and disease biomarkers by finding ways to see proteins more clearly and precisely.

In one of his main projects, Qian is getting ready to analyze samples from hundreds of patients over many time points to get a better grasp of diabetes. "We initially spent almost two years trying to work out the techniques" to prepare for this study, he says. His next challenge will be to help determine "which protein is the most interesting," he adds.

Looking ahead

In the next few years, Qian says that he will continue the diabetes work and expects to focus his technology improvement efforts specifically on studying and understanding that disease. The proteomic analysis of pancreatic islets could help determine why diabetes patients frequently lose these cells, and possibly even how to help recover them, he hopes. He says he would also like to get involved in developing a cancer biomarker discovery project.

Publications of note

A review paper in Molecular & Cellular Proteomics that came out in 2006 entitled "Advances and challenges in liquid chromatography-mass spectrometry-based proteomics profiling for clinical applications" offers a good overview of the hurdles yet to be overcome in the field, Qian says.

Qian was lead author on a paper published in the Journal of Proteome Research in 2005. "Probability-based evaluation of peptide and protein identifications from tandem mass spectrometry and SEQUEST analysis: The human proteome" reports the findings of Qian and collaborators' study of how to assess false positive rates in the identification of peptides by analyzing three human proteome samples. The authors note that false positive rates were higher for peptides identified from human plasma samples than for those identified from human cell lines, and they suggest new filtering criteria to improve confidence in peptide calls.

And the Nobel goes to …

Qian says that he would feel that he had earned a Nobel prize if he could "really identify a protein [that was] a huge therapeutic target, or something resolving some sort of cure for a disease like diabetes — using proteomics, of course."

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