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Cam Patterson, Carolina Cardiovascular Biology Center, on the Heart of Microarrays

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At A Glance:

  • Cam Patterson
  • BA, Vanderbilt University, 1985
  • MD, Emory University School of Medicine,1989
  • 1989-1993 — Resident and Chief Resident, Internal Medicine, Emory University Affiliated Hospitals
  • 1993-1996 — Research Fellow, Cardiovascular Biology Laboratory, Harvard School of Public Health
  • 1997-1999 — Clinical Fellow, Cardiology, The University of Texas Medical Branch at Galveston
  • 1999-Present — Associate Professor and Director of the Carolina Cardiovascular Biology Center, University of North Carolina at Chapel Hill

Cam Patterson, director of the University of North Carolina’s Carolina Cardiovascular Biology Center, is responsible for imple- menting a four-year, $2.5 million NIH grant designed to provide genomics and microarray services to National Heart, Lung and Blood Institute researchers on campus. Through the grant, announced in December, the school has established the Carolina Cardiopulmonary Gene Expression Services microarray core facility in its Lineberger Comprehensive Cancer Center.

BioArray News recently spoke with Patterson, an MD and an associate professor of medicine, pharmacology, and cell and developmental biology, about his goals for helping cardiovascular researchers at UNC engage in microarray-assisted research.

Now that you have this funding, what is on your shopping list?

The center that we are setting up is an expansion of a nice microarray facility set up within the cancer center. What we are planning to do is expand the capacity of the center to account for the needs of scientists who are doing cardiovascular research. Additionally, we are adding front-end and back-end resources for investigators who are interested in microarray applications for cardiovascular research. That includes: both designing experiments and hybridizations, developing techniques for performing microarray analysis on limited sample volumes with amplification protocols; doing in vivo work with small animal models, and developing the bioinformatics platform to help people understand what the 20,000 changes they see [in an experiment] actually mean.

We are doing 20,000-gene spotted arrays using the Compugen oligo library for human and mouse. We are [also] using Agilent oligo arrays, which in our hands, are high quality. They are a little more expensive than home brew, but they save time. And, there are certain advantages to using them as well. The workhorse, however, will be the arrays we make ourselves.

What will your funding buy?

The grant will fund four people for the first year, and six people for the remainder of the funding cycle, in addition to the six or eight people working in the existing facility right now.

Tell me what the funding will enable you to do?

The grant was in response to an RFA from NHLBI for the purpose of making microarray experiments accessible to NHLBI investigators. The expansion that we are devel- oping is primarily to service the 80 investigators who receive funding for heart and blood vessel research, pulmonary, blood, and sleep research. Our goal is to make people who would be intimidated by microarrays try to use them.

Would that be new interfaces on software?

A big component of the grant and of the center is new applications. Our goal, five years from now, is to develop new techniques that not only service users on campus, but elsewhere.

Microarrays seem to be producing results in cancer research. What do you see for the cardiovascular community?

Cardiovascular research follows behind the cancer research community a little in microarray research. The NHLBI wanted to get these centers set up to bridge that gap. We want to see that happen. We are informing ourselves from the progress that has been made. We have challenges that some cancer researchers don’t face. We look at heterogeneous cell populations, far fewer total numbers of cells, and more diversity of those cell populations.

Duke has the Heart Center: Do you see collaborative efforts between you two?

We work closely with cardiovascular scientists and the genomics scientists at Duke. In particular, we have strong collaborations with Pascal Goldschmidt in cardiology and Joe Nevins in the Functional Genomics Center. They have some sophisticated tools over there and a center for bioinformatics. Things are evolving rapidly in terms of the interaction. Also, there are a lot of startup companies that are seeking us out to get access to samples. It’s an exciting time.

Sounds like there is a flourishing community in your corner of the Research Triangle.

It’s a very free-flowing community: We share reagents, we exchange postdocs and technicians. There’s a virtual community of scientists dedicated to gene expression profiling.

How did you first get exposed to microarrays?

I moved from Texas, where I was at the UT Medical Branch, and was [then] recruited to be director of the Carolina Cardiovascular Center. For a short time after I first arrived here, my lab was next to Chuck Perou [UNC assistant professor of genetics who completed post-doctoral studies under David Botstein and Pat Brown at Stanford]. I got a crash course in microarray technology from Chuck. I had previous experience with Affymetrix microarray technology, but working with Chuck really allowed me to take things to a different dimension. Affy technology is good, but in a sense, it’s everything-comes-out-of-the-box, and that hampers people’s ability to design experiments. Custom chips give you much more flexibility and help the cost issues.

What are you doing for data analysis?

We have a mirror of a Stanford database that Chuck set up here. That’s the workhorse of what we do; it’s more sophisticated and has power that doesn’t exist in the off-the-shelf software packages. It’s an Oracle relational database on a SunFire with 200 gigs of active storage. It has TreeView, Cluster, and SNP analysis, as well as more sophisticated custom applications that Chuck has developed. As part of our mission, we are developing software specifically for cardiovascular applications.

How many programmers do you have?

In addition to the three programmers that Chuck has, we have hired one person who has a wonderful background. He is a trained cardiovascular physiologist with a PhD and a master’s in bioinformatics from Memphis.

What are your short-range plans?

We need to prioritize things. Our plan over the first three to six months [is that] we want to optimize in-house protocols so that everything we tell people is correct. We want to set up a microarray users group that serves two functions — users can hear about what we have to offer, and we can hear from them what they plan on doing. We will have a limited number of complete projects this year, maybe five or six, and next year, we will triple and quadruple that. In year two, we hope to have a big jump in the number of investigators using microarrays, and in year three, we will be at full speed.

The big goal of this grant is to bring the technique to investigators who don’t have funding for it. We will cover most of the costs ourselves. And, over the long term, we have plans for cost recovery, but we plan on providing investigators with very inexpensive costs. Custom chips will be the workhorses, since their costs are fairly modest in comparison with those using Affy chips and expensive arrays.

One of the things that we have kept in mind — we are starting a facility right now — [is that] two years from now, we will be creating a huge database that many people will want access to. One of the weird things about microarray data is that a single investigator will not exhaust it. We need to open up that pipeline.

How about data integration between centers?

The NHLBI is very aware of how important that is going to be. The NHLBI has experience with similar types of funding opportunities where they brought investigators together. There will not be 11 centers in isolation: that doesn’t serve the entire community. We ought to get together with the other investigators and we will. A broader issue is how do investigators share their data? Not just cardiovascular biologists who are interested in sharing their data, but across disciplines. We still haven’t figured out what the standard format is going to be, and NCBI is still trying to sort that out. MIAME or whatever, we plan to make sure our data is available to other scientists. One principle of our data is that all data must be available to other investigators at the time of manuscript submission.

What we have done is created a cardiovascular biology center from scratch here at UNC, and I was recruited to start it up. We are here to develop new methods for those already on campus, and the micro-array grant is a reflection we are having some success with that. Recruiting is very successful; I have had pretty high expectations for the center.

We want to make people think that UNC is moving ahead in cardiovascular research. How will we know if we have been successful two or three years from now? The proof will be in the pudding: Go to Medline.

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