Celera is close to completing a pilot study of pancreatic cancer undertaken to prove that its proteomics platform can generate viable drug targets and disease markers, Scott Patterson, Celera’s vice president for proteomics, told ProteoMonitor last week.
The pilot study involved differential protein expression experiments on pancreatic “normal-like” and cancer cell lines, and in the course of the study the proteomics group has identified several protein targets that are still under investigation, Patterson said. These targets fall into four categories: proteins known to be associated with pancreatic cancer; proteins known to be associated with a similar disease, such as lung cancer; proteins characterized previously; and proteins not reported in the literature.
Patterson suggested that Celera would be more likely to develop the targets further if the cell biology groups at Celera and Celera South San Francisco find that one or more of the targets are also found to be associated with other tumor types. “If the targets are worth pursuing, we’ll take them forward,” Patterson said, “but it could be more exciting if they’re found in another tumor type.”
While the cell biology groups at Celera and Celera South San Francisco attempt to validate these targets from the pancreatic cancer study, the proteomics group has already begun a larger initiative to discover novel protein targets associated with lung cancer, Patterson said. This study will involve not just proteins derived from cell cultures, but also tissue and serum samples that will arrive periodically from Celera’s clinical partner, he added.
In identifying the protein targets associated with pancreatic cancer, and now lung cancer, Celera has relied on its multidimensional liquid chromatography and mass spectrometry platform to separate and identify differentially expressed proteins, while also taking advantage of quantitative techniques such as the ICAT reagents. Patterson’s group relies heavily on Applied Biosystems’ Mariner ESI-TOFs for picking out differentially expressed peptides from HPLC fractions, and either ABI/MDS Sciex QSTAR Q-TOF or ABI 4700 Proteomics Analyzer MALDI TOF/TOF mass spectrometers to acquire peptide sequence data using tandem mass spectrometry. Celera has also developed techniques for using small molecule affinity agents to select for druggable protein targets such as kinases and proteases.
Celera has several avenues for further validating the targets that it discovers, including classical gene knockout studies in mice, experiments involving small molecule inhibitors developed at Celera South San Francisco, and the overexpression of “dead” or inactive proteins that “sop up” a protein’s binding agents, Patterson said. Most recently, Patterson said studies using RNAi gene “knockdown” techniques have been shown to be particularly efficient at diminishing the levels of the corresponding protein in the cell.
Indeed, a tour of Celera’s cell biology and proteomics facilities in Rockville, Md., provided evidence that the company is expanding its laboratory capabilities to validate protein targets and handle clinical specimens. A room formerly used as a staging area for other laboratories is now occupied by the cell biology group. In addition, the group now has technology for recombinant protein expression, Patterson said.
But while the company’s cell biology facilities grow, Patterson remained ambiguous about whether his proteomics group’s capacity would grow or shrink in the coming months. Celera’s mass spectrometry facility now contains six of ABI’s MALDI TOF/TOFs, but with Kathy Ordoñez taking over as Celera’s president, “everything is up for review,” Patterson said. “Are we planning a big reduction in scale? No,” he said. “We have a few planned projects [in addition to the lung cancer study] but I don’t have a crystal ball.”