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Doug Conklin on the Growth of RNAi, Life After Cold Spring Harbor

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At A Glance

Name: Doug Conklin

Age: 39

Assistant Professor, University at Albany

Background: Scientists/Researcher, Cold Spring Harbor Lab — 2001-2003 Senior Staff Scientist, Genetica — 1999-2000 Senior Fellow, CSHL — 1997-1999 Postdoc, CSHL — 1993-1996 PhD, Molecular Biology, University of Wisconsin, Madison — 1992

The University at Albany, State University of New York, recently established the Gen*NY*Sis Center for Excellence in Cancer Genomics in conjunction with the state’s Gen*NY*Sis program to advance cancer genomics, systems biology, and disease regulation research. Among the scientists the center has attracted is Doug Conklin, who left Long Island’s Cold Spring Harbor Laboratory last month to continue his RNAi research in upstate New York.

RNAi News spoke with Conklin recently to discuss his past efforts and his plans for the future.

How did you get started in RNA interference?

My interest in it began when I was working at a biotech company [called Genetica] at Cold Spring Harbor [Laboratory]. Basically what we were trying to do is turn tissue culture cells — mammalian cells, in general, whether they were going to be used in vitro or in vivo —we were trying to turn them into something that was genetically tractable, into a system like yeast. The idea was that we’d overexpress genes in these cells … and then also be able to turn genes off or knock them out.

That’s not so easy, and at about that time RNAi was becoming very well known as a tool in C. elegans … and so several people were curious. How prevalent is this? It occurs in plants, it seems to occur in nematodes, does it work in mammalian cells? And so, some people started studying the biochemistry of it, some people started studying the genetics of it, people were jumping from system to system; my interest was just to use it as a tool.

So, there was sort of a convergence of a number of groups working on it … and I just stole it at the last second to use it as a tool.

Is there any particular work going on with RNAi that you feel was the highlight of your time at Cold Spring Harbor Lab?

I think that the main thing was that we’ve taken this quirky phenomenon that … Rich Jorgensen described in plants 12 years ago … and turn that into a tool that’s really useful. And we were able to show that it’s useful in a variety of places in mammalian biology.

The interest here is that it’s a useful tool … it’s also a little interesting that it was a gene regulator phenomenon that people didn’t really know much about. But to be honest with you, I still think that there are a lot of questions about the mechanism of RNAi and those sorts of things that people are still working on.

Now that you are at the University at Albany, what are your first projects going to be?

The work here [is taking place at] a cancer center, it’s a functional genomics center. The idea is just to look at large numbers of candidate genes that might be involved in cancer in some way, and test them functionally … to see what these genes actually do. Do they function in some way that impacts tumorogenesis?

What sorts of genes are you looking at?

In some cases, they are genes that are good bets. So, some of the things I’m starting out with are receptor protein tyrosine kinases. This is a class of genes that has been known for 30 years; there are important members of this family that are involved in causing cancer. There are about 58 of them in the human genome … about half of them are pretty well-known. And then there’s the other half that we don’t know as much about.

So, with this sort of approach you test all of them all at once. and you can start saying: “Oh, this guy’s important for this” or “this guy’s important for that, this guy’s important in this kind of tumor, this guy’s important in that kind of tumor.” Those sorts of things.

So that would be one place where the candidates come from. Just classes of genes that we know exist in the genome, but we just don’t know much about right now …

[As for] the other class of genes …There has been a lot of work done in the last few years on expression profiling, trying to see which genes are over expressed or under expressed under some condition. And, of course, everyone’s favorite condition is genes that are either over or under expressed in tumor cells …

There are, from all these expression profiling experiments, large sets of genes that people don’t know whether they function in this way in tumor cells. And so you could use [RNAi] to go into a tumor cell and take these genes that are over expressed away, one at a time, and then asses the consequences.

How long do these experiments take?

It varies depending on the gene, depending on the phenotype that you’re interested in looking at. So, for some of the more simple phenotypes that people have worked with for a long time, they’re in mammalian cells and mammalian cells grow fairly slowly. But even still, you can tell in a week or two whether or not there’s been some impact on the tumor.

If you want to look in mice or some better models of the disease, it can take months. But the point is, the sooner we start, the sooner we know.

What happens with the discoveries resulting from your work?

The Center for Functional Genomics at the University at Albany was set up by [New York State] Senator Bruno, he’s been a major player behind the scenes, to secure the funding for this [kind of research] …

The idea is that you do cutting-edge molecular biology related to cancer, and that you can rapidly spin off those sorts of discoveries into commercial concerns, which are good for upstate New York and New York, in general.

Are you involved in any sorts of sponsored research arrangements, at this point?

Not yet. That’s a goal.

Where do you hope your work at the Gen*NY*Sis Center will lead?

At one point in my career, and I think at some point in everyone’s career they get really hung up on making an enormous impact on research. And I don’t think that’s going to happen. I think the diseases are going to be cured, cancer is going to be cured … What I would like is to simply be a part of this enormous effort that is going on now.

These are terrible diseases that are going to be cured by lots of people making small contributions. I just want to be able to make small contributions that are going to help. If I can do that, on a personal level, I’m really satisfied.

The thing is I enjoy the work … and that’s the way it works because you don’t make enough money in this business to stick around for the bucks.

What do you see as your biggest challenge to your work going forward? Is there some sort of technological hurdle?

To be honest, I’m still sort of in the halcyon days of just starting out … the hurdles are pretty well-known: getting enough funding, attracting enough people, and going through the typical sorts of promotions you need just to keep things going.

There aren’t so many technological hurdles at this point. The thing is, we’ve just designed this really cool tool, and I think most everybody whose involved with it is just chomping at this bit to use it. It’s still new enough that people haven’t been able to use it to the extent they’d like to. It’s still like tearing the presents open on Christmas morning; we’ve got the train-set set up, and we can’t use it yet.

Do you think that people might be a little overly optimistic about RNAi at this point?

Definitely. Definitely. I certainly think some people are. However, I think a really realistic view of it shows that it’s a vast improvement over what we’ve had. It’s not going to work in all instances in all people, it’s not going to work in all genes, it’s not a universally applicable approach to everything, but it’s … a more powerful tool than what’s come down the pike in a while.

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