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GMU, TGen Form Alliance Combining Proteomic, Genomic Capabilities for Personalized Medicine

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NEW YORK (GenomeWeb) – George Mason University and the Translational Genomics Research Institute this week announced an alliance combining the two institutions' genomic, proteomic, and molecular profiling capabilities for personalized medicine research.

The collaboration will tackle early stage biomarker discovery work as well as more clinical and translational projects with an initial focus in areas including infectious disease, traumatic brain injury, neurodegeneration, and cancer, Emanuel Petricoin and Lance Liotta, co-directors of GMU's Center for Applied Proteomics and Molecular Medicine, told ProteoMonitor.

The agreement emerged from various past collaborations between the two parties, Petricoin said, calling it an "opportunity to really apply a proteogenomics [approach] to disease, combining TGen's best-in-class genomics capabilities with what we think are our best-in-class proteomics capabilities."

By entering a formal alliance, the institutions aim to streamline processes including dividing intellectual property and submitting funding proposals, Liotta said, noting that coordinating among various collaborators can, in looser arrangements, lead to significant "stumbling blocks and delays in terms of getting grants submitted and funded."

The partners said that they have already submitted applications for more than $12 million in grants. Petricoin added that the two institutions have each provided "hundreds of thousand dollars" in funds to get the project started.

One of the most visible examples of prior collaboration between GMU and TGen is the Side-Out Foundation's clinical trials in metastatic breast cancer, for which GMU has done proteomic profiling and TGen has done genomic analyses.

The trials have investigated whether molecularly guided treatment regimens provide improvements over standard of care in metastatic breast cancer patients. Last year, researchers associated with the effort – including Petricoin and Liotta – presented data at the American Society of Clinical Oncology's annual meeting that suggested such personalized approaches could indeed offer benefit.

GMU and TGen are now involved in a second phase of that trial, performing a similar analysis in a larger cohort.

Petricoin said that one ambition of the new collaboration would be to take on similar personalized medicine studies.

"We'd like to have 10 more Side-Out trials, where we are kind of the omics biomarker engine for personalized medicine trials," he said. "We want to position this [alliance such that] if there's an opportunity for personalized medicine biomarker work, if there is a pharmaceutical company out there that is going to incorporate omics markers, then we can be a complete solution for that trial – we have all the omics and informatics capabilities."

On the oncology side, the collaboration will focus initially on breast cancer and melanoma, the latter as part of a Stand Up To Cancer project investigating new therapies for the disease in which TGen has participated since 2011.

The partners also plan to investigate genomic and proteomic biomarkers and new therapies for bone and brain metastases.

Beyond cancer, they are targeting infectious disease, for which Petricoin said they aim to develop markers for things like host response and prediction of vaccine response; and traumatic brain injury and neurodegenerative disease, for which they plan to look for blood and salivary markers for conditions like mild traumatic injury and Alzheimer's.

Regarding the sort of proteomic platforms to be used in the collaboration, reverse phase protein arrays, a technique invented by Petricoin and Liotta and used extensively in their labs, will no doubt have a prominent role, particularly in clinical trial work for which the method's small sample volume requirements make it well suited.

The researchers also aim to incorporate another GMU-developed technology, Ceres Nanosciences' NanoTrap target enrichment product. The technology, which was developed by Petricoin and Liotta along with their GMU colleague Alessandra Luchini, consists of hydrogel nanoparticles with porous outer shells housing chemical affinity baits to various analytes. According to the company – which counts Petricoin and Liotta as members of its scientific advisory board – the particles allow researchers to, for instance, target specific low-abundance proteins, concentrating them up to 1,000-fold while excluding interfering high-abundance proteins.

As such, Petricoin said, the particles could prove useful for the collaborators' biomarker research. In particular, he said, it offered an alternative to immunoenrichment techniques like SISCAPA, which are commonly used to increase the sensitivity of mass spec workflows. Because the NanoTrap technology doesn't require antibodies, it could prove cheaper and faster than immuno-based methods, Petricoin said.

While TGen will primarily focus on the genomic side of things, the organization will also contribute significantly in terms of automated workflows for mass spec sample prep. Specifically, it has built an automated system for SISCAPA sample prep capable of processing roughly 1,000 plasma samples every 24 hours. The researchers have since adapted it for use with the NanoTrap particles, and can currently process roughly 250 plasma samples every 24 hours using this system, Patrick Pirrotte, technical director for TGen's Center for Proteomics, told ProteoMonitor.

However, TGen's mass spec infrastructure is not currently able to keep up with this level of sample prep throughput, Pirrotte said, noting that "typically, following [around] 100 peptide markers using timed [multiple-reaction monitoring assays] on a triple quadrupole instrument with one hour [LC] gradients allow for 16 patient plasma samples per day."

TGen's proteomics researchers are "currently determining the precision and sensitivity of nanoparticle-enriched serum and plasma samples using LC-MRM," he said. He added that whether an immunoenrichment approach like SISCAPA or the nanoparticle-based approach would prove more effective would likely depend on "the type of study and the availability of custom-made antibodies for each marker of interest."

The GMU team is currently optimizing the nanoparticle bait mixtures to cover a broad range of known protein markers, Pirrotte said.

In addition to streamlining research collaborations between the two parties, the alliance will also help with commercialization of any products stemming from it, Petricoin said, characterizing this as a key aspect of the deal.

"Specifically one thing that both [GMU] and TGen are looking forward to is new company creation and commercialization [of new technologies]," he said. The partnership "gives a clearer path for such commercialization should the science suggest it could be useful."

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