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HIP's LaBaer on Using Lumera's Array Platform for Translational Proteomics

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Joshua LaBaer
Director
Harvard Institute
of Proteomics
Lumera recently announced that researchers at the Harvard Institute of Proteomics are using its ProteomicProcessor platform to develop assays that could benefit cancer researchers.
 
Harvard has served as a beta site for Lumera’s platform since the two inked a deal last January, and the Harvard collaboration is focused on integrating its nucleic acid-programmable protein array technology with the ProteomicProcessor to read and analyze the biochip (see BAN 1/10/2006).
 
According to HIP Director Joshua LaBaer, HIP has successfully integrated its NAPPA arrays with the ProteomicProcessor and will begin probing a family of 200 kinase proteins for their interaction with and among drug families relevant to cancer research.
 
To learn more about the collaboration with Lumera and the kinase work, BioArray News spoke with LaBaer this week.
 
Was your foundation predicated on the existence of protein array technology?
 
No, we predated that. Our institute was founded at Harvard Medical School as part of an effort to participate in post-genomic science. The idea was, ‘The genome has been sequenced and we have a lot of information about what genes exist in the genome but relatively little is known about the proteins.’
 
Our concept was from the beginning the idea of doing what we call functional proteomics. So rather that the approach that a lot of people use, which is mass spec-based identification of proteins in samples, our approach has always been to get cloned copies of genes, express proteins, and examine what they do. So [we] do functional experiments with recombinant proteins in a variety of forms.
 
One of the earlier approaches we used, and continue to pursue, was to express proteins in vivo in mammalian tissue culture cells to study effects on phenotypic behavior. And the other approach that we began with was high-throughput protein purification. It was really out of that approach that we decided a better way to do this would be to build an array of proteins. And that is how we developed our protein array technology.
 
So you built your own protein arrays in house?
 
That’s right. Most people who build protein arrays purify the proteins first and then spot the proteins on the array surface. In our technology print[s] the gene for the protein on the array and then the protein is synthesized in situ on the glass surface. They are called nucleic acid-programmable protein arrays, or NAPPA.
 
The beauty of that approach in the eyes of a believer is that [it does not] subject proteins to the purification process, which may in and of itself inactivate some proteins, and then the storage of the proteins, and then the printing of the proteins, and then the storage of the printed proteins, all of which may lead to unfolding and inactivity.  Our proteins are synthesized in situ at the point of the assay, so they are all about as fresh as you can make them. Plus it’s a little bit less difficult and expensive to print proteins that way than to have to purify them first. So that is the approach that we take.
 
But how does Lumera fit into that equation?
 
Lumera is a company with roots in the telecommunications industry. They developed a very rapid optical switch technology that has applications in telecommunications and machine technology. In this context they also recognized that there might also be biological applications for these optical switches. And so they thought of a way to use their optical switch to build a surface plasmon resonance machine.
 
Their technology is really a detection scheme, so their instrument is not [designed] to print or generate proteins. Their technology is to measure proteins that have already been printed. In a sense, our technology complements theirs and vice versa.
They have an instrument that is set up to measure proteins on an array but have no way of generating an array. We have a way of generating an array but we would benefit from a technology that could detect proteins on an array.
 
Once they developed their system, what they realized is that they really needed content. And so they saw a paper in Science and contacted us to license our technology and over time we’ve built this relationship.
 
What does that mean for your research?
 
Our technology is somewhat agnostic to detection schemes. We are doing many experiments using fluorescence detection. However, I think there are outstanding measurements that the Lumera device offers that you cannot get from fluorescent detection or radioactive detection. The beauty of their instrument is that it is label-free so you don’t need to label a probe when you bind it to the proteins on your array. Moreover, you get kinetic information, not just static information. You can actually measure the binding event as it happens in real time. That allows you to assess affinity constants and so on.
 
We think that this is going to be an exciting direction to take in the future because it means that we would not only be able to measure binding events, but their affinities and their off and on rates and so on. It would be very, very powerful.
 
Are you using any protein array technology other than your own?
 
I am very well aware of alternative approaches that are very promising, but we have our own technology and it’s worked quite well for us. We’ve expressed over 10,000 proteins using it so we are moving with that.
 
I understand that you are working on kinase-specific assays that could be useful in cancer research.
 
Our lab has cloned over 500 different human kinases. So we have the vast majority of the members of that class of proteins in hand. Not to mention that that class of proteins is important as a regulatory class and one that plays a key role in some cancers.
 
What we are going to do with the arrays is print arrays of kinases and look at interactions between other proteins and kinases that may play a role in the regulation of those kinases as well as measure small molecules binding to those kinases, although that is going to take a while because SPR in general is not a very sensitive technique.
 
Do you have any translational opportunities down the road? If you do develop assays that are conducive for cancer research, are you in a position where you can work with other institutes in the region?
 
Absolutely. We are a part of the Dana-Farber Harvard Cancer Center. I am a physician myself by training. We are already using our arrays by screening them with serum samples [from] patients to look for biomarkers in cancer and so on. So I think there is a strong interest in our lab to translate this work into clinical studies at some level or another. There’s no doubt that we’ll be able to do that.
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